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1
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Cole DW, Menge TD, Lowe L, Chan MP, Bresler SC. Clinical and Histopathologic Spectrum of Toxic Erythema of Chemotherapy: A Series of 56 Cases From a Single Institution. Am J Dermatopathol 2024; 46:337-345. [PMID: 38133527 DOI: 10.1097/dad.0000000000002450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
INTRODUCTION Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood. OBJECTIVE To provide a comprehensive review of the clinical and histopathologic features of TEC with an emphasis on novel histopathologic findings. METHODS We searched our electronic medical record for "toxic erythema of chemotherapy" or "neutrophilic eccrine hidradenitis." Fifty-six cases meeting clinical and histopathologic criteria were identified. The electronic medical record and accompanying hematoxylin and eosin-stained slides were retrospectively reviewed. RESULTS The clinical findings were heterogeneous but included classic presentations such as intertriginous eruptions (34%) and acral erythema (25%). The most common histopathologic features were apoptotic keratinocytes (95%), basal vacuolar change (91%), and epithelial dysmaturation (79%). Eccrine squamous syringometaplasia was seen in over half of the cases (33/56; 59%), whereas neutrophilic eccrine hidradenitis was uncommon (16%). Interestingly, many cases showed prominent interstitial histiocytes (55%). Other novel findings included irregular orthohyperkeratosis (23%), irregular epidermal hyperplasia (14%), and acantholysis (9%). LIMITATIONS As a retrospective study, it is subject to information bias. CONCLUSION This is the largest reported series of TEC. In addition to confirming previously reported features, we identify novel histopathologic findings to add to the spectrum of TEC.
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Affiliation(s)
- Daniel W Cole
- Department of Dermatology, University of Michigan, Ann Arbor, MI
| | - Tyler D Menge
- Dermatologists Department of Dermatology, VA Ann Arbor Healthcare System, Ann Arbor, MI
- Staff Dermatopathologist, CTA Pathology, Ann Arbor, MI; and
| | - Lori Lowe
- Dermatologists Department of Dermatology and Department of Pathology, University of Michigan, Ann Arbor, MI
| | - May P Chan
- Dermatologists Department of Dermatology and Department of Pathology, University of Michigan, Ann Arbor, MI
| | - Scott C Bresler
- Dermatologists Department of Dermatology and Department of Pathology, University of Michigan, Ann Arbor, MI
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Özhan AK, Demirhan A, Arikoglu T, Karahan F, Satıcı FEG, Tokmeci N, Gündoğan BD, Yalaki Aİ, Akbey V, Karabulut YY, Ünal S, Kuyucu S. Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature. Dermatitis 2024; 35:275-287. [PMID: 38165639 DOI: 10.1089/derm.2023.0258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2-17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens-Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.
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Affiliation(s)
- Aylin Kont Özhan
- From the Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Ali Demirhan
- Department of Pediatric Allergy and Immunology, Mersin City Training and Research Hospital, Mersin, Turkey
| | - Tuğba Arikoglu
- From the Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Feryal Karahan
- Department of Pediatric Hematology and Oncology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | | | - Nazan Tokmeci
- Department of Pediatric Allergy and Immunology, Adıyaman University Training and Research Hospital, Adıyaman, Turkey
| | - Begümhan Demir Gündoğan
- Department of Pediatric Hematology and Oncology, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, İzmir, Turkey
| | - Aysu İlhan Yalaki
- From the Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Veysi Akbey
- From the Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | | | - Selma Ünal
- Department of Pediatric Hematology and Oncology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Semanur Kuyucu
- From the Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey
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Hirakata M, Tomikawa E, Sakai C, Uchida M, Okano T, Shimozono R, Kawai M, Itaba S, Munakata L, Suzuki R, Oshida K. TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome. Toxicol Appl Pharmacol 2024; 485:116912. [PMID: 38521368 DOI: 10.1016/j.taap.2024.116912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 03/05/2024] [Accepted: 03/20/2024] [Indexed: 03/25/2024]
Abstract
Anthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline anti-cancer drug, and modified and optimized polymerized pirarubicin (THP), known as P-THP, is expected to have low toxicity and high efficacy. The anti-cancer effects of TXB-001 were examined using the 4T1 mouse model. An alopecia mouse model and HFS rat model were used to evaluate the alopecia- and HFS-inducing effects of TXB-001 and compare their severity with existing anthracycline anti-cancer drugs. A pharmacokinetic analysis of plasma as well as chest, palmar, and plantar skin samples after the single intravenous administration of DOXIL and TXB-001 to rats was also performed. The results obtained revealed that TXB-001 exerted similar anti-cancer effects to those of DOXIL in mice, weaker alopecia-inducing effects than DOX, DOXIL, and THP in mice, and no or markedly weaker HFS-like changes than DOXIL, which induced significant histopathological changes. The results of the pharmacokinetic analysis showed the accumulation of DOXIL, but not TXB-001, in skin, particularly palmar and plantar skin samples, and these differences were considered to contribute to their HFS-inducing effects.
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Affiliation(s)
- Mikito Hirakata
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
| | - Emi Tomikawa
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
| | - Chizuka Sakai
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
| | - Masashi Uchida
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
| | - Tsubasa Okano
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
| | - Rieko Shimozono
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
| | - Masakatsu Kawai
- Department of Bio Research, Kamakura Techno-Science, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa, 248-0036, Japan
| | - Shoichi Itaba
- Department of Bio Research, Kamakura Techno-Science, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa, 248-0036, Japan
| | - Lisa Munakata
- Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
| | - Ryo Suzuki
- Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
| | - Keiyu Oshida
- Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan..
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Zhang X, Zhang J, Cai Y, Xu S, Wu H, Chen X, Huang Y, Li F. Integrated Electrochemical Aptasensor Array toward Monitoring Anticancer Drugs in Sweat. Anal Chem 2024; 96:4997-5005. [PMID: 38483157 DOI: 10.1021/acs.analchem.4c00297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
In the realm of clinical practice, the concurrent utilization of anticancer medications can enhance their overall therapeutic efficacy. However, it is crucial to acknowledge that the interactions among these anticancer drugs can potentially yield detrimental consequences on their intended outcomes. Consequently, the assessment of both anticancer potency and potential toxic side effects is greatly refined when multiple anticancer drugs are simultaneously detected and evaluated. Here, we designed a wearable electrochemical aptasensor array for monitoring multiple anticancer drugs in sweat. The integrated sensor array consists of three working electrodes modified with three different aptamers (Apt1, Apt2, and Apt3), a Au counter electrode, and a Ag/AgCl reference electrode. Molecular docking simulations were performed to show the binding affinities between three anticancer drugs and their corresponding aptamers. Various eigenvalues were derived from the square-wave voltammetry electrochemical signals, and these data sets were subjected to rigorous analysis through multivariate data analysis techniques. This analytical approach demonstrated exceptional performance by achieving flawless 100% accuracy in the precise identification of nine anticancer drugs consistently at uniform concentrations. Furthermore, the integrated wearable sensor array exhibited impressive capabilities, correctly recognizing all nine anticancer drugs with 100% accuracy and successfully distinguishing between these drugs in artificial sweat samples. The proposed sensor array presents good stability for 15 days. Flexibility tests showed stable device performance after 500 twisting cycles. This innovative wearable sensing array represents a novel approach for achieving real-time monitoring and precise adjustment of drug dosages. It offers invaluable insights for tailoring the treatment of anticancer drugs to individual patients, predicting both drug efficacy and potential adverse reactions within the field of clinical medicine.
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Affiliation(s)
- Xiaoyu Zhang
- Intelligent Agriculture Engineering Laboratory of Anhui Province, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Speed Capability Research, Su Bingtian Center for Speed Research and Training, Jinan University, Guangzhou 510632, China
| | - Jiabing Zhang
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Speed Capability Research, Su Bingtian Center for Speed Research and Training, Jinan University, Guangzhou 510632, China
- Xidian University, Xi'an 710071, China
| | - Ying Cai
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Speed Capability Research, Su Bingtian Center for Speed Research and Training, Jinan University, Guangzhou 510632, China
| | - Siting Xu
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Speed Capability Research, Su Bingtian Center for Speed Research and Training, Jinan University, Guangzhou 510632, China
| | - Hao Wu
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Speed Capability Research, Su Bingtian Center for Speed Research and Training, Jinan University, Guangzhou 510632, China
| | - Xiangyu Chen
- Intelligent Agriculture Engineering Laboratory of Anhui Province, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
| | - Yu Huang
- State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan 430074, China
| | - Fengyu Li
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Speed Capability Research, Su Bingtian Center for Speed Research and Training, Jinan University, Guangzhou 510632, China
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Darvin ME. Optical Methods for Non-Invasive Determination of Skin Penetration: Current Trends, Advances, Possibilities, Prospects, and Translation into In Vivo Human Studies. Pharmaceutics 2023; 15:2272. [PMID: 37765241 PMCID: PMC10538180 DOI: 10.3390/pharmaceutics15092272] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/19/2023] [Accepted: 08/24/2023] [Indexed: 09/29/2023] Open
Abstract
Information on the penetration depth, pathways, metabolization, storage of vehicles, active pharmaceutical ingredients (APIs), and functional cosmetic ingredients (FCIs) of topically applied formulations or contaminants (substances) in skin is of great importance for understanding their interaction with skin targets, treatment efficacy, and risk assessment-a challenging task in dermatology, cosmetology, and pharmacy. Non-invasive methods for the qualitative and quantitative visualization of substances in skin in vivo are favored and limited to optical imaging and spectroscopic methods such as fluorescence/reflectance confocal laser scanning microscopy (CLSM); two-photon tomography (2PT) combined with autofluorescence (2PT-AF), fluorescence lifetime imaging (2PT-FLIM), second-harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), and reflectance confocal microscopy (2PT-RCM); three-photon tomography (3PT); confocal Raman micro-spectroscopy (CRM); surface-enhanced Raman scattering (SERS) micro-spectroscopy; stimulated Raman scattering (SRS) microscopy; and optical coherence tomography (OCT). This review summarizes the state of the art in the use of the CLSM, 2PT, 3PT, CRM, SERS, SRS, and OCT optical methods to study skin penetration in vivo non-invasively (302 references). The advantages, limitations, possibilities, and prospects of the reviewed optical methods are comprehensively discussed. The ex vivo studies discussed are potentially translatable into in vivo measurements. The requirements for the optical properties of substances to determine their penetration into skin by certain methods are highlighted.
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Nara K, Taguchi A, Yamamoto T, Tsuruga T, Tojima Y, Miyamoto Y, Tanikawa M, Sone K, Mori M, Takada T, Suzuki H, Osuga Y. Efficacy of regional cooling + oral dexamethasone for primary prevention of hand-foot syndrome associated with pegylated liposomal doxorubicin. Support Care Cancer 2023; 31:283. [PMID: 37074471 PMCID: PMC10115730 DOI: 10.1007/s00520-023-07718-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 03/31/2023] [Indexed: 04/20/2023]
Abstract
PURPOSE Pegylated liposomal doxorubicin (PLD)-induced hand-foot syndrome (HFS) frequently lowers the quality of life of ovarian cancer patients. Wrist and ankle cooling, having a limited preventive effect, has been the commonest supportive HFS care. In this study, we retrospectively assessed the primary preventive effect of a combination of regional cooling and oral dexamethasone therapy (cooling + oral Dex) on HFS. METHODS This study is a single-arm retrospective, observational study. Recurrent ovarian cancer patients were administered PLD ± bevacizumab. We retrospectively examined the efficacy of hands and feet cooling (from the start of PLD to the end) + oral Dex (day 1-5: 8 mg/day, day 6, 7: 4 mg/day) for primary HFS prevention. RESULTS This study included 74 patients. The initial dose of PLD was 50 mg/m2 and 40 mg/m2 for 32 (43.2%) and 42 (56.8%) patients, respectively. HFS of Grade ≥ 2 and Grade ≥ 3 developed in five (6.8%) and one (1.4%) patient(s), respectively. The incidence of ≥ Grade 2 and ≥ Grade 3 HFS was much lower than those reported in previous studies. Dose reduction was required in 13 patients (17.6%) mainly because of neutropenia or mucositis; there was no HFS-induced dose reduction. Meanwhile, PLD therapy was discontinued mainly because of interstitial pneumonia (4 patients) and HFS (one patient). CONCLUSIONS We demonstrated the efficacy of regional cooling and oral Dex for primary prevention of PLD-induced HFS. Although future prospective studies are needed to confirm its efficacy, this combination therapy can be considered for primary prevention of HFS in ovarian cancer patients on PLD.
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Affiliation(s)
- Katsuhiko Nara
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan
| | - Ayumi Taguchi
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
| | - Takehito Yamamoto
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan
- The Education Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Tetsushi Tsuruga
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Yuri Tojima
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan
| | - Yuichiro Miyamoto
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Michihiro Tanikawa
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Kenbun Sone
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Mayuyo Mori
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Tappei Takada
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan
| | - Hiroshi Suzuki
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
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7
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Sapena V, Iavarone M, Boix L, Facchetti F, Guarino M, Sanduzzi Zamparelli M, Granito A, Samper E, Scartozzi M, Corominas J, Marisi G, Díaz A, Casadei-Gardini A, Gramantieri L, Lampertico P, Morisco F, Torres F, Bruix J, Reig M. Polymorphism AGT2 (rs4762) is involved in the development of dermatologic events: Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib. World J Hepatol 2022; 14:1438-1458. [PMID: 36158918 PMCID: PMC9376774 DOI: 10.4254/wjh.v14.i7.1438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/24/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Dermatologic adverse events (DAEs) are associated with a better outcome in patients with hepatocellular carcinoma (HCC) irrespective of the therapeutic agent received. The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors (TKIs) to the skin or an immune-mediated reaction triggered by the oncologic treatment. As is the case in other conditions, individual genetic variants may partially explain a higher risk of DAEs. AIM To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs. METHODS We first analyzed 27 single-nucleotide polymorphisms (SNPs) from 12 genes selected as potential predictors of adverse event (AE) development in HCC patients treated with sorafenib [Barcelona Clinic Liver Cancer 1 (BCLC1) cohort]. Three additional cohorts were analyzed for AGT1 (rs699) and AGT2 (rs4762) polymorphisms-initially identified as predictors of DAEs: BCLC2 (n = 79), Northern Italy (n = 221) and Naples (n = 69) cohorts, respectively. The relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models, and presented with hazard ratios and their 95% confidence intervals (95%CI). RESULTS The BCLC1 cohort showed that patients with arterial hypertension (AHT) (HR = 1.61; P value = 0.007) and/or AGT SNPs had an increased risk of DAEs. Thereafter, AGT2 (rs4762) AA genotype was found to be linked to a statistically significant increased probability of DAEs (HR = 5.97; P value = 0.0201, AA vs GG) in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage, ECOG-PS, diabetes and AHT. The value of this genetic marker was externally validated in the cohort combining the BCLC1, BCLC2 and Naples cohorts [HR = 3.12 (95%CI: 1.2-8.14), P value = 0.0199, AGT2 (rs4762) AA vs AG genotype and HR = 2.73 (95%CI: 1.18-6.32) P value = 0.0188, AGT2 (rs4762) AA vs GG genotype]. None of the other gene variants tested were found to be associated with the risk of DAE development. CONCLUSION DAE development in HCC patients receiving TKIs could be explained by the AGT2 (rs4762) gene variant. If validated in other anti-oncogenic treatments, it might be considered a good prognosis marker.
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Affiliation(s)
- Víctor Sapena
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
- Universidad de Barcelona, Barcelona 08036, Spain
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, Foundation Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy
| | - Loreto Boix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
| | - Floriana Facchetti
- Gastroenterology and Hepatology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan 20100, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", Napoli 80100, Italy
| | - Marco Sanduzzi Zamparelli
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
- Universidad de Barcelona, Barcelona 08036, Spain
- Department of Clinical Medicine and Surgery, Gastroenterology and Hepatology, Federico II University of Naples, Naples 80131, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Azienda Ospedaliero-Universitaria di Bologna, Bologna 40139, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40139, Italy
| | - Esther Samper
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
| | - Mario Scartozzi
- Department of Medical Oncology, University of Cagliari, Cagliari 45698, Italy
| | - Josep Corominas
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
| | - Giorgia Marisi
- Biosciences Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica, Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori", Meldola 47014, Italy
| | - Alba Díaz
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
- Universidad de Barcelona, Barcelona 08036, Spain
- Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona 08036, Spain
| | - Andrea Casadei-Gardini
- School of Medicine, Vita-Salute San Raffaele University, Milan 20132, Italy
- Unit of Oncology, Università Vita-Salute, Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica-San Raffaele Scientific Institute, Milan 20132, Italy
| | - Laura Gramantieri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Azienda Ospedaliero, Bologna 40138, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Ca' Granda Ospedale Maggiore Policlinico, Milano 20122, Italy
- Department of Pathophysiology and Transplantation, Colorectal Cancer "A. M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milano 20122, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Naples 80131, Italy
| | - Ferran Torres
- Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona 08036, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Cerdanyola 08193, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
- Universidad de Barcelona, Barcelona 08036, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona 08036, Spain
- Universidad de Barcelona, Barcelona 08036, Spain
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Chen L, Wu Z, Yang L, Chen Y, Wang W, Cheng L, Li C, Lv D, Xia L, Chen J, Tang L, Zhang LI, Zhang S, Luo J. Nitric oxide in multikinase inhibitor-induced hand-foot skin reaction. Transl Res 2022; 245:82-98. [PMID: 35189405 DOI: 10.1016/j.trsl.2022.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 01/17/2022] [Accepted: 02/14/2022] [Indexed: 11/13/2022]
Abstract
Hand-foot skin reaction (HFSR) is the most debilitating and prevalent side effect caused by multikinase inhibitors (MKIs) that share vascular endothelial growth factor receptor (VEGFR) as the common inhibition target, such as sorafenib, regorafenib, axitinib, etc. Though not life-threatening, HFSR can significantly deteriorate patients' quality of life and jeopardize the continuity of cancer therapy. Despite years of efforts, there are no FDA-approved treatments for HFSR and the understanding of the precise pathogenic mechanism is still limited. In this study, we hypothesized that nitric oxide has the potential therapeutic effect to reverse the toxicity caused by MKI through upregulation of several VEGF/VEGFR downstream signaling pathways. We found that glyceryl trinitrate (GTN), a nitric oxide donor, could stimulate cell proliferation, migration, and protect cells from apoptosis induced by MKIs in vitro. Local application of GTN mitigated tissue damage in a rat model, while not impacting the anti-tumor effect of the MKI in HepG2 tumor-bearing mice. Finally, GTN ointment alleviated cutaneous damages and improved quality of life in 6 HFSR patients. Our study proposed and validated the mechanism to counteract VEGFR inhibition, providing GTN as the potential treatment to MKI-induced HFSR, which may further improve the therapeutic window of various MKI based cancer therapies.
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Affiliation(s)
- Leying Chen
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Zhaoyu Wu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Linan Yang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yuyun Chen
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Wenhong Wang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Liting Cheng
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Chong Li
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Dazhao Lv
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Liangyong Xia
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jia Chen
- Department of Dermatopathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lina Tang
- Department of Oncology, the 6th People' Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
| | - L I Zhang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China..
| | - Shiyi Zhang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China..
| | - Jie Luo
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China..
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Yoshida Y, Sasaoka S, Tanaka M, Matsumoto K, Inoue M, Satake R, Shimada K, Mukai R, Suzuki T, Iwata M, Goto F, Mori T, Mori K, Yoshimura T, Nakamura M. Analysis of drug-induced hand-foot syndrome using a spontaneous reporting system database. Ther Adv Drug Saf 2022; 13:20420986221101963. [PMID: 35646307 PMCID: PMC9136434 DOI: 10.1177/20420986221101963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 04/23/2022] [Indexed: 12/23/2022] Open
Abstract
Purpose The aim of our study was to assess the clinical features of hand-foot syndrome (HFS) associated with certain systemic chemotherapeutic drugs in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database. Methods HFS was defined using the preferred terms from the Medical Dictionary for Regulatory Activities. We used several indices, such as the reporting odds ratios (RORs) at 95% confidence interval (CI), the time-to-onset profile of HFS, and cluster analysis. Results Of 646,779 reports (submission period: April 2004 to September 2020), 1814 reported HFS events. The RORs (95% CI) for axitinib, capecitabine, lapatinib, regorafenib, sorafenib, and sunitinib were 14.9 (11.1-20.1), 54.6 (49.2-60.6), 130.4 (110.7-153.6), 63.3 (55.2-72.6), 29.0 (25.8-32.7), and 13.9 (11.7-16.5), respectively. The analysis of time-to-onset profiles revealed that the median values (interquartile range: 25.0-75.0%) of drug-induced HFS caused by capecitabine, cisplatin, docetaxel, everolimus, regorafenib, sorafenib, and trastuzumab were 21.0 (13.0-42.0), 15.0 (10.0-82.0), 6.0 (3.0-25.0), 86.5 (67.0-90.5), 9.0 (6.0-14.0), 9.0 (6.0-14.0), and 70.0 (15.0-189.0) days, respectively. The number of clusters was set to 4. Among these, one cluster, which included capecitabine, regorafenib, and lapatinib, exhibited a higher reporting ratio and ROR of drug-induced HFS than other drugs. Conclusions The RORs and results of time-to-onset analysis obtained in this study indicated the potential risk of HFS associated with chemotherapeutic drugs. Our results suggest that health care professionals must be aware of the potential onset of drug-induced HFS with docetaxel, regorafenib, and sorafenib for at least 4 weeks; therefore, careful observation is recommended. Plain Language Summary Elucidation of the relationship between cancer drugs and risk of hand-foot syndrome: Purpose: Hand-foot syndrome (HFS) is an adverse effect of some cancer drugs, which is characterized by symptoms such as redness, swelling, blistering, and pain in the area of palms and soles. HFS reduces the quality of life of patients and can sometimes interfere with anticancer treatment plans. It is important to understand the clinical manifestations of HFS and gain knowledge that will allow for early intervention by clinicians.Methods: In this study, we used a large-scale side effect database of real-world cases for a comprehensive investigation of anticancer-drug-induced HFS. The database contained 646,779 adverse event reports from April 2004 to September 2020; among which, we identified 1814 HFS events. Using these data, we could obtain information on the relationship between 19 types of anticancer drugs and HFS, and the onset time of HFS and HFS prognosis related to each anticancer drug. Results: Our results suggest that clinicians should monitor the risk of HFS with docetaxel, regorafenib, and sorafenib for at least the first 4 weeks after drug administration. Conclusion: These findings are crucial for improving the management of the adverse effects caused by anticancer drugs.
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Affiliation(s)
- Yu Yoshida
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Sayaka Sasaoka
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Mizuki Tanaka
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Kiyoka Matsumoto
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Misaki Inoue
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Riko Satake
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Kazuyo Shimada
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Ririka Mukai
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Takaaki Suzuki
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
- Gifu Prefectural Government, Gifu, Japan
| | - Mari Iwata
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
- Kifune Pharmacy, Gifu, Japan
| | - Fumiya Goto
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Takayuki Mori
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Japan
| | - Koki Mori
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Japan
| | | | - Mitsuhiro Nakamura
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
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Zheng YF, Fu X, Wang XX, Sun XJ, He XD. Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients. World J Clin Cases 2021; 9:10075-10087. [PMID: 34904077 PMCID: PMC8638035 DOI: 10.12998/wjcc.v9.i33.10075] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 09/01/2021] [Accepted: 09/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pegylated liposomal doxorubicin (PLD) uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands, producing toxic free radicals and oxidative damage, resulting in hand-foot syndrome (HFS). Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands; thus, decreasing the incidence and severity of HFS. AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term. METHODS This is a retrospective cohort study. Female breast cancer patients (n = 101) who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group (51 patients) and the control group (50 patients). Patients in the control group only received routine care, while the patients in the cooling group applied cooling patches, based on routine care, to the palm and back of the hands 15 min before chemotherapy infusion for 10 h. All patients took a corresponding dose of dexamethasone orally one day before chemotherapy, on the day of chemotherapy, and one day after chemotherapy. SPSS23.0 version was used to analyze the data in this study. The occurrence and severity of HFS was analyzed by the Mann-Whitney U test, and scores were analyzed by the Student's t test or Wilcoxon rank-sum test. A P value < 0.05 was regarded as statistically significant. RESULTS In this study, neither group of patients developed Grade 3 HFS. In the control group, the incidence of Grade 1 HFS and Grade 2 HFS was 38% and 2%, respectively. However, in the cooling group, only one person developed Grade 1 HFS (2%), and none of the patients developed Grade 2 HFS. These findings showed that cooling patches can effectively reduce the frequency and severity of HFS (P < 0.0001) in the short-term. Before the fourth chemotherapy cycle, although general self-efficacy scale scores in the cooling group were low, they were still significantly higher than those in the control group (17.22 ± 5.16 vs 19.63 ± 6.42, P = 0.041). Compared with the control group, the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower (18.08 ± 7.01 vs 14.20 ± 7.39, P = 0.008). CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term. In addition, it may help delay the decline in patients' self-efficacy.
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Affiliation(s)
- Yan-Fu Zheng
- Department of Breast Oncology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang 110042, Liaoning Province, China
| | - Xin Fu
- Department of Breast Oncology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang 110042, Liaoning Province, China
| | - Xiao-Xu Wang
- Department of Breast Oncology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang 110042, Liaoning Province, China
| | - Xiao-Jing Sun
- Department of Breast Oncology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang 110042, Liaoning Province, China
| | - Xiao-Dan He
- Department of Gynecology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang 110042, Liaoning Province, China
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Recognition and Management of Toxic Erythema of Chemotherapy for the Inpatient Dermatologist. CURRENT DERMATOLOGY REPORTS 2021. [DOI: 10.1007/s13671-021-00344-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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12
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Su X, Zhang X, Liu W, Yang X, An N, Yang F, Sun J, Xing Y, Shang H. Advances in the application of nanotechnology in reducing cardiotoxicity induced by cancer chemotherapy. Semin Cancer Biol 2021; 86:929-942. [PMID: 34375726 DOI: 10.1016/j.semcancer.2021.08.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/03/2021] [Accepted: 08/05/2021] [Indexed: 02/08/2023]
Abstract
Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.
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Affiliation(s)
- Xin Su
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaoyu Zhang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wenjing Liu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xinyu Yang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Na An
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Fan Yang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiahao Sun
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanwei Xing
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Hongcai Shang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
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Chen J, Wang Z. How to conduct integrated pharmaceutical care for patients with hand-foot syndrome associated with chemotherapeutic agents and targeted drugs. J Oncol Pharm Pract 2021; 27:919-929. [PMID: 33874817 DOI: 10.1177/10781552211009291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The objective of this article was to offer practical operational process for pharmacists to successfully conduct integrated pharmaceutical care for patients with hand-foot syndrome associated with chemotherapeutic agents and targeted drugs which may facilitate the work of first-line clinical pharmacist.Data sources: A literature review was conducted in March 2020 of Pubmed, Medline, and EMBASE (2010-2020) using terms such as: hand-foot syndrome, hand-foot skin reaction, palmar-plantar erythrodysesthesia, chemotherapeutic agent, and multikinase inhibitor. Appropriate references from selected articles were also used.Data summary: This paper involves 81 articles including review articles, meta-analysis, and clinical trials which focused on every aspect of hand-foot syndrome, such as manifestation, mechanism, occurrence rate, onset time, patient education, self-monitor scale, and management. Studies were thematically divided into four parts (clinical presentation of HFS, risk stratification, initiation of pharmaceutic care, and management of the adverse reaction). CONCLUSION HFS is one of the common adverse events which was associated with many chemotherapeutic agents and multikinase inhibitor drugs. Although the mechanisms and histopathology may be different, they due share some common clinical manifestations. As part of integrated pharmaceutical care for cancer patients, it is important to conduct patient education about the risk of hand-foot syndrome and basic knowledge about hand-foot syndrome management before initiating anticancer therapy. Once hand-foot syndrome happens, evidence-based management could try. If the hand-foot syndrome is intolerable, dose reduction or discontinuation of the anticancer therapy should be considered.
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Affiliation(s)
- Jiexiu Chen
- Department of Pharmacy, Sichuan Provincial Women's and Children's Hospital, Chengdu, China
| | - Zhuo Wang
- Department of Pharmacy, Changhai Hospital of Shanghai, Shanghai, China
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14
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Liang G, Ma W, Zhao Y, Liu E, Shan X, Ma W, Tang D, Li L, Niu X, Zhao W, Zhang Q. Risk factors for pegylated liposomal doxorubicin-induced moderate to severe hand-foot syndrome in breast cancer patients: assessment of baseline clinical parameters. BMC Cancer 2021; 21:362. [PMID: 33827689 PMCID: PMC8025507 DOI: 10.1186/s12885-021-08028-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 03/12/2021] [Indexed: 12/31/2022] Open
Abstract
Background Hand-foot syndrome (HFS) is a side effect of skin related to pegylated liposomal doxorubicin (PLD) application. Moderate to severe hand-foot syndrome (MSHFS) might have a serious impact on patients’ quality of life and treatment. However, information on risk factors for the development of MSHFS is still limited. To analyze the risk factors for PLD-induced MSHFS in breast cancer patients and constructed a logistic regression prediction model. Methods We conducted a retrospective analysis of breast cancer patients who were treated with a PLD regimen in the Tumor Hospital of Harbin Medical University from January 2017 to August 2019. A total of 26 factors were collected from electronic medical records. Patients were divided into MSHFS (HFS > grade 1) and NMHFS (HFS ≤ grade 1) groups according to the NCI classification. Statistical analysis of these factors and the construction of a logistic regression prediction model based on risk factors. Results A total of 44.7% (206/461) of patients developed MSHFS. The BMI, dose intensity, and baseline Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels in the MSHFS group, as well as good peripheral blood circulation, excessive sweat excretion, history of gallstones, and tumour- and HER2-positive percentages, were all higher than those in the NMHFS group (P < 0.05). The model for predicting the occurrence of MSHFS was P = 1/1 + exp. (11.138–0.110*BMI-0.234*dose intensity-0.018*baseline ALT+ 0.025*baseline AST-1.225*gallstone history-0.681* peripheral blood circulation-1.073*sweat excretion-0.364*with or without tumor-0.680*HER-2). The accuracy of the model was 72.5%, AUC = 0.791, and Hosmer-Lemeshow fit test P = 0.114 > 0.05. Conclusions Nearly half of the patients developed MSHFS. The constructed prediction model may be valuable for predicting the occurrence of MSHFS in patients.
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Affiliation(s)
- Guohua Liang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Wenjie Ma
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Yanfang Zhao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Eryu Liu
- Department of Medical Oncology, General Hospital of Heilongjiang Provincial Agricultural Reclamation Bureau, Harbin, 150081, China
| | - Xiaoyu Shan
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Weiwei Ma
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Dabei Tang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Liru Li
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Xingjian Niu
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Wenhui Zhao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
| | - Qingyuan Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
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Hu X, Dong M, Liang X, Liu Z, Li Q. Reactive Oxygen Species-Mediated Inflammation and Apoptosis in Hand-Foot Syndrome Induced by PEGylated Liposomal Doxorubicin. Int J Nanomedicine 2021; 16:471-480. [PMID: 33500617 PMCID: PMC7822082 DOI: 10.2147/ijn.s280187] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/28/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Doxil® (PEGylated liposomal doxorubicin, PLD) has been widely used in cancer treatment due to its excellent therapeutic efficacy, but it can simultaneously cause severe adverse effects such as hand-foot syndrome (HFS). To date, the pathophysiologic mechanism of HFS development induced by PLD administration has not been well understood. MATERIALS AND METHODS The histological features of skin lesion in PLD-induced HFS model were characterized by hematoxylin and eosin (H&E) staining and picrosirius red staining, and the induction of inflammation and apoptosis in the epidermal layer was detected by immunohistochemical and TUNEL staining. Moreover, the generation of reactive oxygen species (ROS) was determined to elucidate the potential mechanism of skin lesion in the development of HFS. RESULTS The administration of PLD has been demonstrated to induce the histological damage of skin tissues including the destruction of collagen fibers and the induction of severe inflammation and apoptosis of epidermal cells. The mechanism was probably attributed to the accumulation of PLD in the skin tissues during the long-term circulation and further the induction of ROS to cause the oxidative damage of keratinocytes owing to the sustained release of doxorubicin from PLD. CONCLUSION The ROS generation induced by the administration of PLD has been identified to be a crucial factor in the development of HFS, which could be used as a potential therapeutic target to alleviate the HFS symptom of PLD administration.
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Affiliation(s)
- Xiaolin Hu
- Cancer Center, The First Hospital of Jilin University, Changchun130012, People’s Republic of China
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun130012, People’s Republic of China
| | - Mengmeng Dong
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun130012, People’s Republic of China
| | - Xiao Liang
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun130012, People’s Republic of China
| | - Ziling Liu
- Cancer Center, The First Hospital of Jilin University, Changchun130012, People’s Republic of China
| | - Quanshun Li
- Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun130012, People’s Republic of China
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Jung S, Darvin ME, Schleusener J, Thiede G, Lademann J, Braune M, Maiwald M, Sumpf B, Tränkle G, Kutzer D, Elban F, Fuss H. In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy. Skin Res Technol 2020; 26:301-307. [PMID: 31903691 DOI: 10.1111/srt.12800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 09/05/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. METHODS Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase ) and immediately after intravenous application of the chemotherapy (T1 ). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength-tunable diode laser-based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. RESULTS Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase . An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. CONCLUSION The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co-medication.
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Affiliation(s)
- Sora Jung
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Maxim E Darvin
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Johannes Schleusener
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Gisela Thiede
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Juergen Lademann
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Marcel Braune
- Ferdinand-Braun-Institut, Leibniz-Institut für Höchstfrequenztechnik, Berlin, Germany
| | - Martin Maiwald
- Ferdinand-Braun-Institut, Leibniz-Institut für Höchstfrequenztechnik, Berlin, Germany
| | - Bernd Sumpf
- Ferdinand-Braun-Institut, Leibniz-Institut für Höchstfrequenztechnik, Berlin, Germany
| | - Günther Tränkle
- Ferdinand-Braun-Institut, Leibniz-Institut für Höchstfrequenztechnik, Berlin, Germany.,Fakultät IV, Technische Universität Berlin, Berlin, Germany
| | - Dunja Kutzer
- Department Hematology and Oncology, Helios Klinikum Bad Saarow, Bad Saarow, Germany
| | - Felia Elban
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Harald Fuss
- Department Hematology and Oncology, Helios Klinikum Bad Saarow, Bad Saarow, Germany
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Ferreira MN, Ramseier JY, Leventhal JS. Dermatologic conditions in women receiving systemic cancer therapy. Int J Womens Dermatol 2019; 5:285-307. [PMID: 31909148 PMCID: PMC6938835 DOI: 10.1016/j.ijwd.2019.10.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 10/12/2019] [Accepted: 10/13/2019] [Indexed: 12/24/2022] Open
Abstract
As advances in cancer therapies have improved cancer-related survival, novel therapeutics have also introduced a variety of dermatologic toxicities, and an increased number of patients are living with these sequalae. Women with cancer in particular experience a spectrum of dermatologic conditions that affect their skin, hair, nail, and mucosal surfaces. Studies have shown that these toxic effects can significantly affect quality of life and alter a woman's self-image, cultural identity, femininity, sexuality, and mental health. In severe instances, dermatologic toxicities may even disrupt cancer therapy and can therefore affect overall survival and treatment response. In this article, we review the dermatologic adverse effects from traditional chemotherapy, targeted therapy, immune checkpoint inhibitors, and endocrine therapy that disproportionately affect women. The timely diagnosis and management of these dermatologic conditions is crucial in the multidisciplinary care of women with cancer.
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Ai L, Xu Z, Yang B, He Q, Luo P. Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management. Expert Rev Clin Pharmacol 2019; 12:1121-1127. [PMID: 31679411 DOI: 10.1080/17512433.2019.1689122] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Sorafenib is a multitargeted tyrosine kinase inhibitor, which has been mainly used in the treatment of advanced hepatocellular carcinoma and renal cancer. However, hand-foot skin reaction (HFSR), as one of the most common adverse reactions, have hindered its long-term clinical application. At present, the mechanism of its occurrence has not been clearly studied and it leads to the lack of effective means of intervention. This article reviews known mechanism and management methods of HFSR caused by sorafenib.Areas covered: The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed.Expert opinion: There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and even survival. Future research should focus on the mechanism of HFSR to find out new ways for prevention. Precautionary measures before the occurrence of HFSR can also be studied in the future.
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Affiliation(s)
- Leilei Ai
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Ziheng Xu
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Bo Yang
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Qiaojun He
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Peihua Luo
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
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19
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Pease DF, Peterson BA, Gilles S, Hordinsky MK, Bohjanen KA, Skubitz KM. Development of cutaneous squamous cell carcinoma after prolonged exposure to pegylated liposomal doxorubicin and hand-foot syndrome: a newly recognized toxicity. Cancer Chemother Pharmacol 2019; 84:217-221. [PMID: 31041511 DOI: 10.1007/s00280-019-03849-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Accepted: 04/22/2019] [Indexed: 12/18/2022]
Abstract
Pegylated liposomal doxorubicin (PLD) can be administered for prolonged periods with minimal toxicity. The risk of cutaneous squamous cell carcinoma (SCC) with this therapy has not been reported. We describe cutaneous SCC of the plantar foot in two patients exposed to high doses of PLD. A 50-year-old man with angiosarcoma received a total PLD dose of 1350 mg/m2 and developed cutaneous SCC of bilateral plantar feet. A 45-year-old woman with cutaneous T-cell lymphoma was treated with a total PLD dose of 1142 mg/m2 with subsequent diagnosis of cutaneous SCC of the right plantar foot. No risk factors for SCC of the plantar foot were identified in either patient. Cutaneous SCC is likely an unreported side effect of prolonged exposure to PLD. An extended duration of hand-foot syndrome from other anti-cancer drugs may also share this risk. Regular complete skin examination with early intervention for suspicious lesions is indicated in this patient population.
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Affiliation(s)
- Daniel F Pease
- Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.,Hennepin County Medical Center, Minneapolis, MN, USA
| | - Bruce A Peterson
- Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Scott Gilles
- Department of Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.,, Thedacare, Appleton, WI, USA
| | - Maria K Hordinsky
- Department of Dermatology, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Kimberly A Bohjanen
- Department of Dermatology, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Keith M Skubitz
- Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
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20
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Totsuka M, Watanabe Y, Asai C, Takahashi S, Ishikawa H, Takamura N, Hagiwara M, Aihara M. Case of severe bullous erythema including intertrigo-like eruptions with angioedema induced by pegylated liposomal doxorubicin. J Dermatol 2019; 46:535-539. [PMID: 31021010 DOI: 10.1111/1346-8138.14895] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 03/28/2019] [Indexed: 11/29/2022]
Abstract
Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. There are only a few reports on intertrigo-like eruptions caused by PLD. We describe the first case of severe bullous erythema, including intertrigo-like eruptions with angioedema, induced by PLD in Japan. We present the case of a 53-year-old woman who was diagnosed with stage IIIC ovarian cancer. After receiving three cycles of PLD, the patient developed swelling of the upper lip and painful erythema with blisters and erosions on the axilla, upper back, flank and wrists. The patient was diagnosed with angioedema and severe skin lesions, including intertrigo-like eruptions induced by PLD. Although treatment with oral prednisolone and topical steroids was effective against these eruptions, the administration of PLD was discontinued because of its ineffectiveness against the primary disease. Several risk factors, such as obesity, perspiration and racial differences, may contribute toward a severe manifestation such as that seen in our patient. Moreover, our case was the first accompanied by angioedema. The mechanism of coexistence of intertrigo-like eruptions and angioedema is not clear; further studies are required to clarify the pathological mechanism of intertrigo-like eruptions.
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Affiliation(s)
- Michiru Totsuka
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yuko Watanabe
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Chika Asai
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Saki Takahashi
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hideyuki Ishikawa
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Naoko Takamura
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Mayumi Hagiwara
- Department of Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Michiko Aihara
- Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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21
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Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem Cell Transplant Recipients. Am J Clin Dermatol 2019; 20:55-73. [PMID: 30298481 DOI: 10.1007/s40257-018-0391-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Hematopoietic stem cell transplants (HSCTs) are used to treat a variety of conditions, including hematologic malignancies, bone marrow failure syndromes, and immunodeficiencies. Over 60,000 HSCTs are performed annually worldwide, and the numbers continue to increase. Indeed, as new conditioning regimens develop, more and more individuals, including those of older age, will be eligible for transplants. Nevertheless, although HSCTs are clearly a life-saving and necessary treatment for thousands of patients per year, there is still substantial morbidity and mortality associated with the procedure. Of note, skin eruptions in the post-HSCT period are frequent and often significantly reduce quality of life in recipients. Moreover, these cutaneous findings sometimes herald an underlying systemic condition, presenting possible opportunities for timelier intervention. Dermatologists therefore play a vital role in distinguishing life-threatening conditions from benign issues and prompting recognition of critical complications earlier in their course. This article aims to review the major dermatologic conditions occurring in the early post-HSCT period.
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Seghers AC, Tey HL, Tee SI, Cao T, Chong WS. Pegylated liposomal doxorubicin-induced miliaria crystallina and lichenoid follicular eruption. Indian J Dermatol Venereol Leprol 2018; 84:121. [PMID: 28513486 DOI: 10.4103/0378-6323.206233] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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23
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Miolo G, Baldo P, Bidoli E, Lombardi D, Scalone S, Sorio R, Veronesi A. Incidence of Palmar-Plantar Erythrodysesthesia in Pretreated and Unpretreated Patients Receiving Pegylated Liposomal Doxorubicin. TUMORI JOURNAL 2018; 95:687-90. [DOI: 10.1177/030089160909500608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims and Background Association between pegylated liposomal doxorubicin-based regimens and palmar-plantar erythrodysesthesia have just been emphasized, whereas the relationship between previous treatment and palmar-plantar erythrodysesthesia is still a matter of discussion. We evaluate the relationship between previous chemotherapy treatments and the development of palmar-plantar erythrodysesthesia in patients receiving pegylated liposomal doxorubicin-based regimens. Methods Between January 2005 and November 2006, 92 patients received regimens including pegylated liposomal doxorubicin. Patients were divided into three groups based on pegylated liposomal doxorubicin dosing interval length, different dose chosen, and previous chemotherapy. Results Among pretreated patients receiving regimens including 30 mg/m2 of pegylated liposomal doxorubicin repeated every three weeks, the incidence of palmar-plantar erythrodysesthesia was not significantly higher than in unpretreated patients receiving the same weekly schedule ( P = 0.4). There was no difference in the incidence of palmar-plantar erythrodysesthesia between pretreated patients with regimens including 30 mg/m2 of pegylated liposomal doxorubicin every three weeks and pretreated patients receiving 20 mg/m2 of pegylated liposomal doxorubicin every two weeks ( P = 0.8). The prevalence of palmar-plantar erythrodysesthesia observed in the unpretreated group exposed to 30 mg/m2 every three weeks was comparable to that of the pretreated group receiving 20 mg/m2 biweekly ( P = 0.3). However, excluding all the patients who developed grade 1 palmar-plantar erythrodysesthesia, the incidence of grade 2 and 3 palmar-plantar erythrodysesthesia observed in pretreated patients receiving regimens including 20 mg/m2 of pegylated liposomal doxorubicin biweekly was significantly higher than in unpretreated patients receiving 30 mg/m2 of pegylated liposomal doxorubicin every three weeks ( P = 0.001). Conclusions Our findings indicate that the pretreatment is not involved in the increased incidence of any grade palmar-plantar erythrodysesthesia. On the contrary, the study could suggest that the type of previous treatment may be an important factor in the development of more severe forms of palmar-plantar erythrodysesthesia.
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Affiliation(s)
- GianMaria Miolo
- Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Paolo Baldo
- Pharmacy Unit, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Ettore Bidoli
- Epidemiology Unit, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Davide Lombardi
- Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Simona Scalone
- Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Roberto Sorio
- Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Andrea Veronesi
- Division of Medical Oncology C, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
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Fukuda A, Tahara K, Hane Y, Matsui T, Sasaoka S, Hatahira H, Motooka Y, Hasegawa S, Naganuma M, Abe J, Nakao S, Takeuchi H, Nakamura M. Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. PLoS One 2017; 12:e0185654. [PMID: 28953936 PMCID: PMC5617225 DOI: 10.1371/journal.pone.0185654] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 09/16/2017] [Indexed: 01/10/2023] Open
Abstract
Doxorubicin (DOX) is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS) databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS). This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ) database. We also calculated the reporting odds ratios (RORs) of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX). The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI) from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89–13.68), 6.43 (5.81–7.13), and 14.73 (11.42–18.99), respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI) for palmar-plantar erythrodysesthesia (PPE) associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74–9.07), 64.77 (56.84–73.80), and 28.76 (15.77–52.45), respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome DOX formulations.
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Affiliation(s)
- Akiho Fukuda
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Kohei Tahara
- Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu University, Gifu-shi, Gifu, Japan
| | - Yuuki Hane
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Toshinobu Matsui
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Sayaka Sasaoka
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Haruna Hatahira
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Yumi Motooka
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Shiori Hasegawa
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Misa Naganuma
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Junko Abe
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
- Medical database Co., LTD, Shibuya-ku, Tokyo, Japan
| | - Satoshi Nakao
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
| | - Hirofumi Takeuchi
- Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu University, Gifu-shi, Gifu, Japan
| | - Mitsuhiro Nakamura
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan
- * E-mail:
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25
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Jung S, Sehouli J, Chekerov R, Kluschke F, Patzelt A, Fuss H, Knorr F, Lademann J. Prevention of palmoplantar erythrodysesthesia in patients treated with pegylated liposomal doxorubicin (Caelyx®). Support Care Cancer 2017; 25:3545-3549. [PMID: 28653108 DOI: 10.1007/s00520-017-3781-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 06/07/2017] [Indexed: 12/30/2022]
Abstract
PURPOSE Palmoplantar erythrodysesthesia (PPE) is one of the most frequent side effects during systemic treatment with pegylated liposomal doxorubicin (PLD, Caelyx®). PPE lesions show a range of symptoms, from numbness to painful erosions, and can have a major impact on the quality of life in affected patients. Previously, a possible pathomechanism of PPE was found in doxorubicin-treated patients based on radical formation in the skin. Here, a preventive strategy using a topically applied ointment with a high radical protection factor was investigated. METHODS In this randomized placebo-controlled double-blind study the antioxidant-containing ointment was compared with a placebo ointment regarding PPE grade III occurrence, overall PPE grade I-III occurrence and PPE severity in PLD patients. The verum or placebo cream was topically applied for a period of 16 weeks, starting 3 days prior to the first cycle of chemotherapy. Clinical evaluations were carried out by a dermatologist prior to the first cycle of chemotherapy and every 4 weeks for the duration of 16 weeks. RESULTS Thirty-two patients were enrolled in total, of which 17 (66%) completed the study. No PPE grade III was found in the verum group, while five out of seven patients (71%) had to be unblinded in the placebo arm due to PPE grade III (p = 0.003). General PPE occurrence of all grades was 60% under verum and 86% under placebo treatment. CONCLUSIONS The preventive application of an antioxidant-containing ointment was shown to be significantly more effective in the prevention of PPE grade III compared to placebo treatment.
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Affiliation(s)
- S Jung
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
| | - J Sehouli
- Department of Gynaecology and Obstetrics, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - R Chekerov
- Department of Gynaecology and Obstetrics, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - F Kluschke
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - A Patzelt
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - H Fuss
- Department of Hematology, Oncology and Palliative Care, Helios Klinikum Bad Saarow, Bad Saarow, Germany
| | - F Knorr
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - J Lademann
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Bailey EB, Merriman J, Maughan B, Poole A, Tantravahi SK, Agarwal AM, Batten JA, Patel SB, Pal SK, Stenehjem DD, Agarwal N. Effect of treatment dose reductions in the setting of hand-foot syndrome on survival outcomes in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor receptor inhibitors. J Oncol Pharm Pract 2017; 24:190-197. [PMID: 28436250 DOI: 10.1177/1078155217693426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Purpose Hand-foot syndrome is a common dose limiting toxicity of vascular endothelial growth factor receptor tyrosine kinase inhibitors used for treatment of patients with metastatic renal cell carcinoma. The effect of treatment dose reductions, in the context of hand-foot syndrome, on survival outcomes is reported. Methods This was a retrospective case series of patients receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors from 1 January 2004 to 31 October 2013. The main outcomes were progression-free and overall survival in these patients experiencing hand-foot syndrome and undergoing treatment dose reductions. Univariate and multivariate analyses were conducted utilizing Kaplan-Meier method and COX Proportional Hazard model with landmark analyses at 2 months. Results Of the 120 patients evaluated, treatment dose reductions for any reason were required in 68 (56.7%) patients. The most common reasons for treatment dose reductions were mucositis, hand-foot syndrome, and fatigue. The median progression-free survival and overall survival were significantly longer in patients with hand-foot syndrome with or without treatment dose reductions as compared to those without hand-foot syndrome. Conclusions An improvement in survival outcomes was observed in metastatic renal cell carcinoma patients with treatment-associated hand-foot syndrome despite treatment dose reductions. These data need validation in a larger cohort to confirm the hypothesis that treatment dose reductions in the setting of hand-foot syndrome do not negatively impatient survival.
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Affiliation(s)
- Erin B Bailey
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Joseph Merriman
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Benjamin Maughan
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Austin Poole
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | | | - Archana M Agarwal
- 2 Department of Pathology, The University of Utah & ARUP Laboratories, Salt Lake City, UT, USA
| | - Julia A Batten
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Shiven B Patel
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Sumanta K Pal
- 3 Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - David D Stenehjem
- 4 Pharmacotherapy Outcomes Research Center, College of Pharmacy, The University of Utah, Salt Lake City, UT, USA
| | - Neeraj Agarwal
- 1 The University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
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Sasaoka S, Matsui T, Abe J, Umetsu R, Kato Y, Ueda N, Hane Y, Motooka Y, Hatahira H, Kinosada Y, Nakamura M. [Evaluation of the Association of Hand-Foot Syndrome with Anticancer Drugs Using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) Databases]. YAKUGAKU ZASSHI 2017; 136:507-15. [PMID: 26935094 DOI: 10.1248/yakushi.15-00222] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The Japanese Ministry of Health, Labor, and Welfare lists hand-foot syndrome as a serious adverse drug event. Therefore, we evaluated its association with anticancer drug therapy using case reports in the Japanese Adverse Drug Event Report (JADER) and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). In addition, we calculated the reporting odds ratio (ROR) of anticancer drugs potentially associated with hand-foot syndrome, and applied the Weibull shape parameter to time-to-event data from JADER. We found that JADER contained 338224 reports from April 2004 to November 2014, while FAERS contained 5821354 reports from January 2004 to June 2014. In JADER, the RORs [95% confidence interval (CI)] of hand-foot syndrome for capecitabine, tegafur-gimeracil-oteracil, fluorouracil, sorafenib, and regorafenib were 63.60 (95%CI, 56.19-71.99), 1.30 (95%CI, 0.89-1.89), 0.48 (95%CI, 0.30-0.77), 26.10 (95%CI, 22.86-29.80), and 133.27 (95%CI, 112.85-157.39), respectively. Adverse event symptoms of hand-foot syndrome were observed with most anticancer drugs, which carry warnings of the propensity to cause these effects in their drug information literature. The time-to-event analysis using the Weibull shape parameter revealed differences in the time-dependency of the adverse events of each drug. Therefore, anticancer drugs should be used carefully in clinical practice, and patients may require careful monitoring for symptoms of hand-foot syndrome.
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Affiliation(s)
- Sayaka Sasaoka
- Laboratory of Drug Informatics, Gifu Pharmaceutical University
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Kubicka-Wołkowska J, Kędzierska M, Lisik-Habib M, Potemski P. Skin toxicity in a patient with ovarian cancer treated with pegylated liposomal doxorubicin: A case report and review of the literature. Oncol Lett 2016; 12:5332-5334. [PMID: 28105242 DOI: 10.3892/ol.2016.5309] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 07/15/2016] [Indexed: 11/06/2022] Open
Abstract
Pegylated liposomal doxorubicin (PLD) is a form of doxorubicin enclosed in pegylated liposomes. In contrast to conventional doxorubicin, PLD is characterized by a lower incidence of cardiotoxicity and myelosuppression. However, it induces specific mucocutaneous side effects, particularly palmar-plantar erythrodysesthesia (PPE). Other dermal manifestations, such as intertrigo-like dermatitis, diffuse follicular rash, melanotic macules, maculopapular rash or recall phenomenon are less common. Mechanisms that lead to skin toxicity remain unclear, however, certain reports indicate that drug excretion in sweat, host-vs.-altered-host reactions and local mechanical microtrauma play an important role in the development of cutaneous disorders. Effective preventive and curative management has not yet been established. The current study reports a case of a 55-year-old patient with advanced ovarian cancer who developed an uncommon diffuse maculopapular rash and severe PPE during treatment with PLD. Complete regression of the skin disorder was observed after 4 weeks. At present, palliative chemotherapy provides the opportunity to prolong life and alleviate disease symptoms, nonetheless it produces a number of adverse effects. Dermal complications may affect patient quality of life and cause therapy interruption. In the light of widespread use of PLD, skin toxicity associated with this drug creates a major problem.
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Affiliation(s)
- Joanna Kubicka-Wołkowska
- Department of Chemotherapy, Medical University of Lodz, Copernicus Memorial Hospital, Lodz 93-513, Poland
| | - Magdalena Kędzierska
- Department of Chemotherapy, Medical University of Lodz, Copernicus Memorial Hospital, Lodz 93-513, Poland
| | - Maja Lisik-Habib
- Department of Chemotherapy, Medical University of Lodz, Copernicus Memorial Hospital, Lodz 93-513, Poland
| | - Piotr Potemski
- Department of Chemotherapy, Medical University of Lodz, Copernicus Memorial Hospital, Lodz 93-513, Poland
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Nikolaou V, Syrigos K, Saif MW. Incidence and implications of chemotherapy related hand-foot syndrome. Expert Opin Drug Saf 2016; 15:1625-1633. [PMID: 27718746 DOI: 10.1080/14740338.2016.1238067] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Hand-foot syndrome (HFS) is a well-established cutaneous adverse event of certain chemotherapeutic agents, mainly capecitabine, continuously infused 5-fluorouracil, docetaxel and pegylated liposomal doxorubicin. Erythema, dysesthesia, pain, cracking and desquamation located on palms and soles are the most characteristic manifestations. Although HFS is a reversible and non-life-threatening clinical condition, it can often affect patient's quality of life significantly, hence necessitating therapeutic modifications or even treatment discontinuation. Areas covered: This is review article on current data regarding the clinical characteristics, grading and management of HFS. Special focus has been given to recent literature studying novel therapeutic strategies. Expert opinion: Early recognition, patient education and supportive measures are considered as the key elements in the management of HFS. Up to date, treatment interruption and dose intensity reduction are the mainstay of HFS management. Many topical formulations and systemic treatment regimens have been proposed, with COX-2 inhibitors being the most promising agents. Nevertheless, large prospective randomized controlled trials are needed in order to agree on solid, evidence-based treatment algorithms.
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Affiliation(s)
- V Nikolaou
- a Oncology Unit, Third Department of Medicine , Athens Medical School, Sotiria General Hospital , Athens , Greece
| | - K Syrigos
- a Oncology Unit, Third Department of Medicine , Athens Medical School, Sotiria General Hospital , Athens , Greece
| | - M W Saif
- b GI Oncology Experimental Therapeutic , Tufts Medical Center, Tufts Cancer Center , Boston , MA , USA
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Lou Y, Wang Q, Zheng J, Hu H, Liu L, Hong D, Zeng S. Possible Pathways of Capecitabine-Induced Hand–Foot Syndrome. Chem Res Toxicol 2016; 29:1591-1601. [PMID: 27631426 DOI: 10.1021/acs.chemrestox.6b00215] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Yan Lou
- The
First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310000, People’s Republic of China
| | - Qian Wang
- The
First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310000, People’s Republic of China
| | - Jinqi Zheng
- Zhejiang Institute for Food and Drug Control, Hangzhou, Zhejiang 310004, People’s Republic of China
| | - Haihong Hu
- Laboratory
of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province
Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical
Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
| | - Lin Liu
- The
First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310000, People’s Republic of China
| | - Dongsheng Hong
- The
First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310000, People’s Republic of China
| | - Su Zeng
- Laboratory
of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province
Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical
Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
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Chanprapaph K, Rutnin S, Vachiramon V. Multikinase Inhibitor-Induced Hand-Foot Skin Reaction: A Review of Clinical Presentation, Pathogenesis, and Management. Am J Clin Dermatol 2016; 17:387-402. [PMID: 27221667 DOI: 10.1007/s40257-016-0197-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Multikinase inhibitors (MKIs) are targeted cancer therapies designed to inhibit multiple tyrosine kinase pathways responsible for tumor proliferation, growth, and survival. These agents are more able to target cancer cells and possess better safety profiles than conventional chemotherapies. However, MKIs can produce significant cutaneous adverse events, hand-foot skin reaction (HFSR) being the most clinically significant. Although not life threatening, HFSR can lead to MKI dose modification, interruption, or termination, potentially limiting the anti-tumor effect. This article summarizes the current knowledge concerning the epidemiology, clinical presentation, pathogenesis, histopathology, prognostic implication, and current evidence-based prophylactic and reactive treatment options for MKI-induced HFSR. Its high incidence and significant impact on the quality of life emphasizes the great need to understand the pathogenesis and improve management of this condition.
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Affiliation(s)
- Kumutnart Chanprapaph
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand.
| | - Suthinee Rutnin
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand
| | - Vasanop Vachiramon
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand
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Huang MD, Fuss H, Lademann J, Florek S, Patzelt A, Meinke MC, Jung S. Detection of capecitabine (Xeloda®) on the skin surface after oral administration. JOURNAL OF BIOMEDICAL OPTICS 2016; 21:47002. [PMID: 27117193 DOI: 10.1117/1.jbo.21.4.047002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 04/01/2016] [Indexed: 06/05/2023]
Abstract
Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m 2 /day 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb 40±10 ppb (2±0.5 pM 2±0.5 pM ) before capecitabine administration to 27.7±11.8 ppm 27.7±11.8 ppm (14.6±6.5 nM 14.6±6.5 nM ) after application, p<0.001 p<0.001 . The results show the secretion of capecitabine on the skin surface after oral administration, indicating a local toxic effect as a possible pathomechanism of PPE.
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Affiliation(s)
- Mao-Dong Huang
- Leibniz-Institut für Analytische Wissenschaften-ISAS-e. V., Albert-Einstein-Straße 9, 12489 Berlin, Germany
| | - Harald Fuss
- Helios Klinikum, Department of Hematology, Oncology and Palliative Care, Pieskower Street 33, 15526 Bad Saarow-Pieskow, Germany
| | - Jürgen Lademann
- Charité-Universitätsmedizin Berlin, Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charitéplatz1, 10117 Berlin, Germany
| | - Stefan Florek
- Leibniz-Institut für Analytische Wissenschaften-ISAS-e. V., Albert-Einstein-Straße 9, 12489 Berlin, Germany
| | - Alexa Patzelt
- Charité-Universitätsmedizin Berlin, Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charitéplatz1, 10117 Berlin, Germany
| | - Martina C Meinke
- Charité-Universitätsmedizin Berlin, Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charitéplatz1, 10117 Berlin, Germany
| | - Sora Jung
- Charité-Universitätsmedizin Berlin, Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charitéplatz1, 10117 Berlin, Germany
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Hofheinz RD, Gencer D, Schulz H, Stahl M, Hegewisch-Becker S, Loeffler LM, Kronawitter U, Bolz G, Potenberg J, Tauchert F, Al-Batran SE, Schneeweiss A. Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group. J Clin Oncol 2015; 33:2444-9. [DOI: 10.1200/jco.2014.60.4587] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Purpose Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine. Patients and Methods Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses. Results A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment. Conclusion This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine.
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Affiliation(s)
- Ralf-Dieter Hofheinz
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Deniz Gencer
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Holger Schulz
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Michael Stahl
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Susanna Hegewisch-Becker
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Luisa Mantovani Loeffler
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Ursula Kronawitter
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Georg Bolz
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Jochem Potenberg
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Felix Tauchert
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Salah-Eddin Al-Batran
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
| | - Andreas Schneeweiss
- Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus
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Wolf R, Tüzün Y. Baboon syndrome and toxic erythema of chemotherapy: Fold (intertriginous) dermatoses. Clin Dermatol 2015; 33:462-5. [DOI: 10.1016/j.clindermatol.2015.04.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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McLellan B, Ciardiello F, Lacouture ME, Segaert S, Van Cutsem E. Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management. Ann Oncol 2015; 26:2017-26. [PMID: 26034039 PMCID: PMC4576906 DOI: 10.1093/annonc/mdv244] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/12/2015] [Indexed: 12/13/2022] Open
Abstract
Regorafenib is an oral multikinase inhibitor licensed for use in gastrointestinal cancers. In clinical trials, regorafenib showed a consistent toxicity profile, including clinically significant hand–foot skin reaction (HFSR). Treatment modifications and symptomatic measures, as recommended in this review, can be used to manage HFSR and help patients to continue treatment at an optimal dose. Background Regorafenib is an orally available, small-molecule multikinase inhibitor with international marketing authorizations for use in colorectal cancer and gastrointestinal stromal tumors. In clinical trials, regorafenib showed a consistent and predictable adverse-event profile, with hand–foot skin reaction (HFSR) among the most clinically significant toxicities. This review summarizes the clinical characteristics of regorafenib-related HFSR and provides practical advice on HFSR management to enable health care professionals to recognize, pre-empt, and effectively manage the symptoms, thereby allowing patients to remain on active therapy for as long as possible. Design This review is based on a systematic literature search of the PubMed database (using synonyms of HFSR, regorafenib, and skin toxicities associated with targeted therapies or cytotoxic chemotherapy). However, as this search identified very few articles, the authors also use their clinical experience as oncologists and dermatologists managing patients with treatment-related HFSR to provide recommendations on recognition and management of HFSR in regorafenib-treated patients. Results Regorafenib-related HFSR is similar to that seen with other multikinase inhibitors (e.g. sorafenib, sunitinib, cabozantinib, axitinib, and pazopanib) but differs from the hand–foot syndrome seen with cytotoxic chemotherapies (e.g. fluoropyrimidines, anthracyclines, and taxanes). There have been no controlled trials of symptomatic management of regorafenib-related HFSR, and limited good-quality evidence from randomized clinical trials of effective interventions for HFSR associated with other targeted therapies. Recommendations on prevention and management of regorafenib-related HFSR in this review are therefore based on the expert opinion of the authors (dermatologists and oncologists with expertise in the management of treatment-related skin toxicities and oncologists involved in clinical trials of regorafenib) and tried-and-tested empirical experience with other multikinase inhibitors and cytotoxic chemotherapies. Conclusions As recommended in this review, treatment modifications and supportive measures to prevent, reduce, and manage HFSR can allow patients to continue regorafenib at the optimal dose to derive benefit from treatment.
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Affiliation(s)
- B McLellan
- Albert Einstein College of Medicine and Jacobi Medical Center, Bronx, USA
| | - F Ciardiello
- Seconda Università degli Studi di Napoli, Napoli, Italy
| | - M E Lacouture
- Memorial Sloan Kettering Cancer Center, New York, USA
| | - S Segaert
- University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - E Van Cutsem
- University Hospitals Leuven and KU Leuven, Leuven, Belgium
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Jung S, Sehouli J, Patzelt A, Lademann J. Influence of mechanical stress on palmoplantar erythrodysesthesia--a case report. Oncol Res Treat 2015; 38:42-4. [PMID: 25765506 DOI: 10.1159/000370343] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Accepted: 11/26/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND Cutaneous adverse events can have an important negative influence on quality of life and compliance in affected patients. Palmoplantar erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated with chemotherapeutic treatment, which necessitates treatment interruption or dose reduction in severe cases. This case report of pegylated liposomal doxorubicin-induced PPE shows the influence of mechanical stress on the development of skin lesions in various locations and the importance of patient education and compliance. CASE REPORT We present the case of a 43-year-old female patient diagnosed with ovarian cancer and having undergone surgical and chemotherapeutic treatment. The development of extensive grade 3 PPE affecting numerous areas of the body particularly exposed to mechanical pressure necessitated dermatological treatment. The combination of local application of an antioxidant-containing ointment and the patient's compliance made it possible to continue chemotherapy without interruption or dose reduction. CONCLUSION The development of PPE often limits the use of chemotherapeutic agents, and this case report can provide a possible therapeutic and preventive strategy for affected patients.
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Affiliation(s)
- Sora Jung
- Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany
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Toxicity Management of Renal Cell Cancer Patients on Targeted Therapies. KIDNEY CANCER 2015. [DOI: 10.1007/978-3-319-17903-2_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Najem A, Deregnaucourt D, Ramdane S, Dridba M, Djouba F, Vercambre-Darras S. Intertrigo-Like Dermatitis With Pegylated Liposomal Doxorubicin: Diagnosis and Management. J Clin Oncol 2014; 32:e104-6. [DOI: 10.1200/jco.2013.48.7470] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Abeer Najem
- Dr Duchenne Hospital, Boulogne-sur-Mer, France
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40
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Fas/Fas Ligand Mediates Keratinocyte Death in Sunitinib-Induced Hand-Foot Skin Reaction. J Invest Dermatol 2014; 134:2768-2775. [DOI: 10.1038/jid.2014.218] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Revised: 03/24/2014] [Accepted: 04/07/2014] [Indexed: 01/27/2023]
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Palaniappan M, Srinivasamurthy S, Dubashi B, Chandrasekaran A. Anticancer drug induced palmar plantar erythrodysesthesia. J Clin Diagn Res 2014; 8:HC01-3. [PMID: 25478366 DOI: 10.7860/jcdr/2014/9133.4975] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Accepted: 07/02/2014] [Indexed: 12/28/2022]
Abstract
BACKGROUND Palmar plantar erythrodysesthesia (PPE) is a dose limiting toxicity of anticancer agents. In some cases it may mandate for discontinuation of anticancer agents. Evaluation of data of PPE among reported adverse drug reactions (ADRs) from the Department of Medical Oncology could quantify the burden. AIM To evaluate and analyse the PPE among reported ADRs from medical Oncology. MATERIALS AND METHODS The data of all cases of reported PPE were collected during January 2012 to September 2013 and were analysed with WHO causality assessment scale. The severity was clinically graded. The follow-up data regarding outcome of ADRs were also noted. RESULTS During the study period of 21 months a total of 1418 ADRs have been reported from 1076 patients. Among them PPE was reported from 31 cases (2.9%). Majority (32.2%) of these patients were on chemotherapy for breast cancer. Patient's age ranged from 17 to 68 y and the median age was 50 y. There were 18 female (58%) and 13 male patients (42%). Capecitabine was the leading drug involved in PPE, reported with 20 cases (64.5%), and followed by docetaxel with 5 cases (16.1%). Majority (67.7%) of the reactions was categorized as certain and 64.5% was grade II severity clinically. CONCLUSION Our findings show that PPE accounts for 2.9% of total reported ADRs from Medical Oncology during 21 months. Majority of the reactions were classified as certain. Capecitabine is commonly implicated drug.
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Affiliation(s)
- Muthiah Palaniappan
- Technical Associate - Pharmacovigilance, Department of Clinical Pharmacology, JIPMER , Pondicherry, India
| | | | - Biswajit Dubashi
- Assistant Professor, Department of Medical Oncology, JIPMER , Pondicherry, India
| | - Adithan Chandrasekaran
- Head of the Department, Department of Clinical Pharmacology, JIPMER , Pondicherry, India
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Lademann J, Röwert-Huber HJ, Haas N, Kluschke F, Patzelt A, Zastrow L, Lange-Asschenfeldt B, Jung S, Sterry W, Sehouli J. Palmoplantar erythrodysesthesia-like skin symptoms in patients under various chemotherapeutics: preventive and therapeutic options. Skin Pharmacol Physiol 2014; 27:229-33. [PMID: 24802288 DOI: 10.1159/000356780] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 10/25/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients. METHODS 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment. RESULTS At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued. CONCLUSION The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation.
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Affiliation(s)
- Juergen Lademann
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Templeton AJ, Ribi K, Surber C, Sun H, Hsu Schmitz SF, Beyeler M, Dietrich D, Borner M, Winkler A, Müller A, von Rohr L, Winterhalder RC, Rochlitz C, von Moos R, Zaman K, Thürlimann BJK, Ruhstaller T. Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08). Breast 2014; 23:244-9. [PMID: 24656636 DOI: 10.1016/j.breast.2014.02.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Revised: 11/25/2013] [Accepted: 02/14/2014] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin. PATIENTS AND METHODS An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar's matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%. RESULTS Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events. CONCLUSION Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer.
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Affiliation(s)
| | | | - Christian Surber
- Spirig Pharma Schweiz and Dermatologische Universitätsklinik, Basel, Switzerland
| | - Hong Sun
- Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
| | | | - Michael Beyeler
- Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
| | - Daniel Dietrich
- Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
| | - Markus Borner
- Medical Oncology, Spitalzentrum AG, Biel, Switzerland
| | | | | | - Lukas von Rohr
- Medical Oncology, Kantonsspital Aarau, Aarau, Switzerland
| | | | | | - Roger von Moos
- Medical Oncology, Kantonsspital Graubünden, Chur, Switzerland
| | - Khalil Zaman
- Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials. Support Care Cancer 2014; 22:1585-93. [PMID: 24463616 DOI: 10.1007/s00520-014-2129-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 01/13/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE Hand-foot syndrome (HSF) is a distinctive adverse event relatively frequent to some chemotherapeutic agents as capecitabine, pegylated liposomal doxorubicin, sorafenib and other tyrosine-kinase inhibitors. Since the prevention of HFS would be crucial to avoid treatment interruptions and delays, many studies have been conducted with this purpose. METHODS The aim of this systematic review and meta-analysis was to analyze the clinical efficacy of prevention strategies for HFS, through a wide search of electronic databases as well as congress abstracts. The endpoints evaluated were the dichotomic data for mild (Grade 1), moderate to severe (Grades 2 to 3) and all-grade HFS. Meta-analysis was calculated through RevMan v5.1 software. RESULTS Amongst 295 studies identified, only ten met the inclusion criteria. Celecoxib prevented both moderate to severe (odds ratio [OR] 0.39, 95 % confidence interval [CI] 0.20-0.73, P = 0.003) and all-grade HFS (OR 0.47, 95 % CI 0.29-0.78, P = 0.003), whereas pyridoxine and topical urea/lactic acid formulations failed to prove efficacy. There were no proven benefits in mild HFS. The use of topical antiperspirant has not been shown to improve results, according to a single trial. CONCLUSIONS From all available possibilities for the prevention of HFS, celecoxib appears to be the most promising, with statistically significant results. Larger, multicentric studies are required to reinforce this finding.
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Lankheet NAG, Huitema ADR, Mallo H, Adriaansz S, Haanen JBAG, Schellens JHM, Beijnen JH, Blank CU. The effect of seasonal variation and secretion of sunitinib in sweat on the development of hand-foot syndrome. Eur J Clin Pharmacol 2013; 69:2065-72. [PMID: 23995862 DOI: 10.1007/s00228-013-1579-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Accepted: 08/14/2013] [Indexed: 01/01/2023]
Abstract
BACKGROUND Hand-foot syndrome (HFS) is a side effect of sunitinib with considerable impact on quality of life. Seasonal variation and hyperhydrosis are possibly correlated to occurrence of HFS. Therefore, we proposed to study the prevalence of HFS in different seasons retrospectively and to study the relationship between sunitinib sweat secretion and HFS prospectively. PATIENTS AND METHODS A retrospective cohort of 19 patients treated with sunitinib was used to determine seasonal prevalence of HFS. In a prospective study, sunitinib and N-desethyl sunitinib levels in sweat patches of 25 patients treated with sunitinib were quantified and correlated to severity of HFS. RESULTS In the retrospective cohort, the patients suffered from more severe HFS during summertime compared with the rest of the year. In the prospective study, the cumulative amounts of sunitinib plus metabolite measured in the patches of the on-treatment phase (median 129.4 ng/patch) were higher than the off-treatment phase (median 39.5 ng/patch). A tendency was observed towards increasing amounts of drug per patch with increasing severity of HFS. CONCLUSION Patients experienced more HFS in summer time compared to other seasons. However, no statistically significant correlation between sunitinib sweat secretion and severity of HFS could be demonstrated within our patient cohort.
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Affiliation(s)
- Nienke A G Lankheet
- Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands,
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Dy GK, Adjei AA. Understanding, recognizing, and managing toxicities of targeted anticancer therapies. CA Cancer J Clin 2013; 63:249-79. [PMID: 23716430 DOI: 10.3322/caac.21184] [Citation(s) in RCA: 232] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 02/21/2013] [Accepted: 02/25/2013] [Indexed: 12/11/2022] Open
Abstract
Answer questions and earn CME/CNE Advances in genomics and molecular biology have identified aberrant proteins in cancer cells that are attractive targets for cancer therapy. Because these proteins are overexpressed or dysregulated in cancer cells compared with normal cells, it was assumed that their inhibitors will be narrowly targeted and relatively nontoxic. However, this hope has not been achieved. Current targeted agents exhibit the same frequency and severity of toxicities as traditional cytotoxic agents, with the main difference being the nature of the toxic effects. Thus, the classical chemotherapy toxicities of alopecia, myelosuppression, mucositis, nausea, and vomiting have been generally replaced by vascular, dermatologic, endocrine, coagulation, immunologic, ocular, and pulmonary toxicities. These toxicities need to be recognized, prevented, and optimally managed.
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Affiliation(s)
- Grace K Dy
- Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA
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Poi MJ, Berger M, Lustberg M, Layman R, Shapiro CL, Ramaswamy B, Mrozek E, Olson E, Wesolowski R. Docetaxel-induced skin toxicities in breast cancer patients subsequent to paclitaxel shortage: a case series and literature review. Support Care Cancer 2013; 21:2679-86. [PMID: 23686402 DOI: 10.1007/s00520-013-1842-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Accepted: 05/07/2013] [Indexed: 10/26/2022]
Abstract
PURPOSE As the result of a recent national shortage in paclitaxel, some patients who were receiving or scheduled to receive weekly paclitaxel were converted to every 3-week (q3w) docetaxel with granulocyte colony-stimulating factor support. Our institution noted higher than expected incidence of severe skin toxicity events attributable to docetaxel during the shortage period among our breast cancer patients. In this report, we summarize the clinical course of the first five cases, review the literature surrounding docetaxel-induced skin toxicity, and offer possible prevention and treatment strategies to improve docetaxel tolerability. METHODS The observation period for this case series was August 1 through October 21, 2011. All patients treated with docetaxel were identified from our electronic medical record. Operable stage I-III breast cancer patients who received ≥ 1 dose of docetaxel monotherapy at 75-100 mg/m(2) q3w were included in this study. The cases of grade 3-4 docetaxel-induced skin toxicities identified by the treating oncologists were then contacted and signed an informed consent through an Institutional Review Board-approved protocol. RESULTS Thirty-four patients met the inclusion criteria. Five patients (14.7 %) experienced grade 3 skin toxicity events attributable to docetaxel, a significantly higher rate than previously reported for docetaxel dosed at 75-100 mg/m(2). CONCLUSIONS Docetaxel-induced dermatologic toxicity is well characterized; nonetheless, its etiology is largely unknown and evidence-based prevention and management strategies are lacking. This report shows that the use of docetaxel 75-100 mg/m(2) q3w subsequent to dose-dense doxorubicin and cyclophosphamide regimen can lead to unacceptable rate of severe skin toxicity.
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Affiliation(s)
- Ming J Poi
- Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, 300 W 10th Ave, Columbus, OH, 43210, USA
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Modeling the human skin barrier--towards a better understanding of dermal absorption. Adv Drug Deliv Rev 2013; 65:152-68. [PMID: 22525516 DOI: 10.1016/j.addr.2012.04.003] [Citation(s) in RCA: 169] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2011] [Revised: 04/03/2012] [Accepted: 04/09/2012] [Indexed: 12/29/2022]
Abstract
Many drugs are presently delivered through the skin from products developed for topical and transdermal applications. Underpinning these technologies are the interactions between the drug, product and skin that define drug penetration, distribution, and elimination in and through the skin. Most work has been focused on modeling transport of drugs through the stratum corneum, the outermost skin layer widely recognized as presenting the rate-determining step for the penetration of most compounds. However, a growing body of literature is dedicated to considering the influence of the rest of the skin on drug penetration and distribution. In this article we review how our understanding of skin physiology and the experimentally observed mechanisms of transdermal drug transport inform the current models of drug penetration and distribution in the skin. Our focus is on models that have been developed to describe particular phenomena observed at particular sites of the skin, reflecting the most recent directions of investigation.
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Fischer A, Wu S, Ho AL, Lacouture ME. The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta-analysis. Invest New Drugs 2013; 31:787-97. [DOI: 10.1007/s10637-013-9927-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 01/06/2013] [Indexed: 10/27/2022]
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Assaf C, Becker JC, Beyer M, Cozzio A, Dippel E, Klemke CD, Kurschat P, Weichenthal M, Stadler R. Treatment of advanced cutaneous T-cell lymphomas with non-pegylated liposomal doxorubicin - Consensus of the lymphoma group of the Working Group Dermatologic Oncology. J Dtsch Dermatol Ges 2013; 11:338-47. [DOI: 10.1111/ddg.12012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Accepted: 11/06/2012] [Indexed: 11/28/2022]
Affiliation(s)
- Chalid Assaf
- Department of Dermatlogy; Helios Clinic Krefeld; Germany
| | - Jürgen C. Becker
- Department of Dermatology and Venereology; University of Graz; Austria
| | - Marc Beyer
- Department of Dermatolgogy, Venereology and Allergology; CharitÈ - University Medicine Berlin; Germany
| | - Antonio Cozzio
- Department of Dermatology; University Clinic Zurich; Switzerland
| | - Edgar Dippel
- Department of Dermatolgoy; Municipal Clinic Ludwigshaven; Germany
| | | | - Peter Kurschat
- Department of Dermatology and Venereology; University of Cologne; Germany
| | | | - Rudolf Stadler
- Department of Dermatolgy; Johannes Wesling Clinic Minden; Germany
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