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Staruch M, Speth MM, Neyer P, Riesterer O, Aebersold DM, Stieb S. Radiation-associated changes in saliva composition of head and neck cancer patients: A systematic review. Radiother Oncol 2024; 196:110279. [PMID: 38648994 DOI: 10.1016/j.radonc.2024.110279] [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: 09/08/2023] [Revised: 04/04/2024] [Accepted: 04/11/2024] [Indexed: 04/25/2024]
Abstract
Xerostomia is a common radiation-associated toxicity in patients with head and neck cancer. Although several studies examined the decrease in saliva production due to radiotherapy (RT) and investigated the factors associated with this side effect, little is known about the change in radiation-associated saliva composition. This systematic review is the first to summarize existing data and give an overview of the change in pH/buffer capacity, electrolytes, proteins, enzymes, and mucins due to radiation to the salivary glands. Literature search was performed in PubMed and Embase with 47 articles finally eligible for the review, analyzing the saliva composition at several time points before, during and/or after RT, or comparing findings in irradiated patients to a healthy control group. Overall, RT leads to a substantial decrease in salivary pH and buffer capacity. For sodium, chloride and calcium ion, as well as amylase, an increased concentration or activity during RT was reported in most of the studies, followed by a subsequent decrease either already during RT or after the end of treatment. Different trends have been described for the total protein concentration during and after RT. Lactoferrin, however, increased considerably, especially in the first phase of RT. Mucin 5B (MUC5B) concentrations showed a slight increase during RT and concentrations around baseline values again six months post-radiotherapy.
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Affiliation(s)
- Michal Staruch
- Radiation Oncology Center KSA-KSB, Cantonal Hospital Aarau, Aarau, Switzerland; Department of Radiation Oncology, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Marlene M Speth
- Otorhinolaryngology, Cantonal Hospital Aarau, Aarau, Switzerland
| | - Peter Neyer
- Department of Laboratory Medicine, Cantonal Hospital Aarau, Aarau, Switzerland
| | - Oliver Riesterer
- Radiation Oncology Center KSA-KSB, Cantonal Hospital Aarau, Aarau, Switzerland
| | - Daniel M Aebersold
- Department of Radiation Oncology, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Sonja Stieb
- Radiation Oncology Center KSA-KSB, Cantonal Hospital Aarau, Aarau, Switzerland.
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2
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Nayak SG, George A, Sharan K, Nayak BS, Salins N. Interventions to improve quality of life in patients with head and neck cancers receiving radiation therapy: a scoping review. Support Care Cancer 2023; 32:31. [PMID: 38102525 DOI: 10.1007/s00520-023-08197-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 11/20/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND Quality of life (QOL) is impaired in patients with head and neck cancers (HNC) due to illness and treatment-associated morbidity. Although there is evidence from the studies on interventions' role in improving QOL receiving radiation therapy, these are not systematically synthesised. In this scoping review, we searched and synthesised the evidence on interventions to improve the QOL and its impact among patients with HNCs. METHODS This scoping review was conducted using the framework proposed by Arksey and O'Malley, and the extensions suggested by Levac et al. were incorporated. Two reviewers independently searched four electronic databases using key thesaurus and free-text terms, and the data was extracted, tabulated, synthesised and reported as categories. RESULTS Seventy-nine papers reported various interventions of diverse nature such as pharmacological, physical, nutritional, complementary and alternative therapies, psychosocial, oral care related, laser and photobiomodulation therapies, rehabilitative, educational, technology-based, surgical, device-related and nurse lead interventions. Most studies reported clinically meaningful impact of interventions on QOL, although the outcome differences were often statistically insignificant. Few studies reported a combination of interventions to address the multidimensional concerns faced by patients with HNCs. None of the studies examined the impact of interventions on QOL among long-term survivors of HNCs. CONCLUSION As QOL concerns in patients with HNCs are multifaceted, more extensive studies with complex multi-component interventions and robust research designs are warranted.
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Affiliation(s)
- Shalini Ganesh Nayak
- Manipal College of Nursing, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Anice George
- Manipal College of Nursing, Manipal Academy of Higher Education, Manipal, Karnataka, India.
| | - Krishna Sharan
- Radiotherapy & Oncology, KS Hegde Medical Academy, Nitte (Deemed to Be University), Mangalore, Karnataka, India
| | - Baby S Nayak
- Department of Child Health Nursing, Manipal College of Nursing, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Naveen Salins
- Department of Palliative Medicine and Supportive Care, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
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3
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Nathan CAO, Asarkar AA, Entezami P, Corry J, Strojan P, Poorten VV, Makitie A, Eisbruch A, Robbins KT, Smee R, St John M, Chiesa-Estomba C, Winter SC, Beitler JJ, Ferlito A. Current management of xerostomia in head and neck cancer patients. Am J Otolaryngol 2023; 44:103867. [PMID: 36996514 DOI: 10.1016/j.amjoto.2023.103867] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023]
Abstract
Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.
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Affiliation(s)
- Cherie-Ann O Nathan
- Department of Otolaryngology/Head and Neck Surgery, LSU Health Sciences Center, Shreveport, LA, USA; Otolaryngology Section, Surgical Service, Overton Brooks VA Medical Center, Shreveport, LA, USA.
| | - Ameya A Asarkar
- Department of Otolaryngology/Head and Neck Surgery, LSU Health Sciences Center, Shreveport, LA, USA
| | - Payam Entezami
- Department of Otolaryngology/Head and Neck Surgery, LSU Health Sciences Center, Shreveport, LA, USA; Otolaryngology Section, Surgical Service, Overton Brooks VA Medical Center, Shreveport, LA, USA
| | - June Corry
- Department of Radiation Oncology, Genesiscare St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Primoz Strojan
- Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
| | - Vincent Vander Poorten
- Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, Section Head and Neck Oncology, KU Leuven, Leuven, Belgium
| | - Antti Makitie
- Department of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Avraham Eisbruch
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - K T Robbins
- Department of Otolaryngology/Head and Neck Surgery, Southern Illinois University, School of Medicine, Springfield, IL, USA
| | - Robert Smee
- Department of Radiation Oncology, The Prince of Wales Cancer Centre, Sydney, NSW, Australia
| | - Maie St John
- Department of Otolaryngology/Head and Neck Surgery, UCLA, CA, USA
| | - Carlos Chiesa-Estomba
- Otorhinolaryngology - Head & Neck Department - Donostia University Hospital, Biodonostia Research Institute, Deusto University, Spain
| | - Stuart C Winter
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | | | - Alfio Ferlito
- International Head and Neck Scientific Group, Padua, Italy
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Sardellitti L, Bortone A, Filigheddu E, Serralutzu F, Milia EP. Xerostomia: From Pharmacological Treatments to Traditional Medicine-An Overview on the Possible Clinical Management and Prevention Using Systemic Approaches. Curr Oncol 2023; 30:4412-4426. [PMID: 37232794 DOI: 10.3390/curroncol30050336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/16/2023] [Accepted: 04/22/2023] [Indexed: 05/27/2023] Open
Abstract
Despite high incidence rates and severe complications, the management of xerostomia lacks clinical guidelines. The aim of this overview was to summarize the clinical experience derived from the last 10 years of treatments and prevention using systemic compounds. Results showed that the cytoprotective drug amifostine, and its antioxidant agents, are the most discussed as preventive agents of xerostomia in head and neck cancer (HNC) patients. In the presence of the disease, the pharmacological treatments have been mainly directed to stimulate secretion of the damaged salivary glands, or to counteract a decreased capacity of the antioxidant system, in view of an increasing of reactive oxygen species (ROS). However, the data demonstrated low ability of the drugs, together with a great number of side effects, which strongly limit their use. Concerning traditional medicine (TM), valid clinical trials are so limited that neither the efficacy nor the absence of interferences to concomitant chemical therapies can be validated. Consequently, the management of xerostomia and its devastating complications remain a very significant void in daily clinical practice.
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Affiliation(s)
- Luigi Sardellitti
- Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
- Dental Unit, Head and Neck Department, Azienda Ospedaliero Universitaria, 07100 Sassari, Italy
| | - Antonella Bortone
- Dental Unit, Head and Neck Department, Azienda Ospedaliero Universitaria, 07100 Sassari, Italy
| | - Enrica Filigheddu
- Dental Unit, Head and Neck Department, Azienda Ospedaliero Universitaria, 07100 Sassari, Italy
| | - Francesca Serralutzu
- Institute for Animal Production Systems in the Mediterranean Environment (ISPAAM)-Section of Sassari, 07100 Sassari, Italy
| | - Egle Patrizia Milia
- Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
- Dental Unit, Head and Neck Department, Azienda Ospedaliero Universitaria, 07100 Sassari, Italy
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Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands. BIOLOGY 2023; 12:biology12020305. [PMID: 36829582 PMCID: PMC9953449 DOI: 10.3390/biology12020305] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/17/2023]
Abstract
Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE's components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG.
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Liu Z, Dong L, Zheng Z, Liu S, Gong S, Meng L, Xin Y, Jiang X. Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress. Antioxidants (Basel) 2021; 10:antiox10111666. [PMID: 34829539 PMCID: PMC8614677 DOI: 10.3390/antiox10111666] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/14/2021] [Accepted: 10/19/2021] [Indexed: 12/24/2022] Open
Abstract
Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries. These clinical symptoms seriously reduce a patient’s quality of life. Therefore, it is important to clarify the mechanism of SG injury caused by radiotherapy. Although the mechanism of radiation-induced SG injury has not yet been determined, recent studies have shown that the mechanisms of calcium signaling, microvascular injury, cellular senescence, and apoptosis are closely related to oxidative stress. In this article, we review the mechanism by which radiotherapy causes oxidative stress and damages the SGs. In addition, we discuss effective methods to prevent and treat radiation-induced SG damage.
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Affiliation(s)
- Zijing Liu
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; (Z.L.); (L.D.); (Z.Z.); (S.L.); (S.G.)
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China
| | - Lihua Dong
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; (Z.L.); (L.D.); (Z.Z.); (S.L.); (S.G.)
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China
| | - Zhuangzhuang Zheng
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; (Z.L.); (L.D.); (Z.Z.); (S.L.); (S.G.)
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China
| | - Shiyu Liu
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; (Z.L.); (L.D.); (Z.Z.); (S.L.); (S.G.)
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China
| | - Shouliang Gong
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; (Z.L.); (L.D.); (Z.Z.); (S.L.); (S.G.)
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China
| | - Lingbin Meng
- Department of Hematology and Medical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China;
| | - Xin Jiang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; (Z.L.); (L.D.); (Z.Z.); (S.L.); (S.G.)
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China
- Correspondence: ; Tel.: +86-158-0430-2750
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7
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Fuloria S, Subramaniyan V, Karupiah S, Kumari U, Sathasivam K, Meenakshi DU, Wu YS, Guad RM, Udupa K, Fuloria NK. A Comprehensive Review on Source, Types, Effects, Nanotechnology, Detection, and Therapeutic Management of Reactive Carbonyl Species Associated with Various Chronic Diseases. Antioxidants (Basel) 2020; 9:1075. [PMID: 33147856 PMCID: PMC7692604 DOI: 10.3390/antiox9111075] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/26/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022] Open
Abstract
Continuous oxidation of carbohydrates, lipids, and amino acids generate extremely reactive carbonyl species (RCS). Human body comprises some important RCS namely hexanal, acrolein, 4-hydroxy-2-nonenal, methylglyoxal, malondialdehyde, isolevuglandins, and 4-oxo-2- nonenal etc. These RCS damage important cellular components including proteins, nucleic acids, and lipids, which manifests cytotoxicity, mutagenicity, multitude of adducts and crosslinks that are connected to ageing and various chronic diseases like inflammatory disease, atherosclerosis, cerebral ischemia, diabetes, cancer, neurodegenerative diseases and cardiovascular disease. The constant prevalence of RCS in living cells suggests their importance in signal transduction and gene expression. Extensive knowledge of RCS properties, metabolism and relation with metabolic diseases would assist in development of effective approach to prevent numerous chronic diseases. Treatment approaches for RCS associated diseases involve endogenous RCS metabolizers, carbonyl metabolizing enzyme inducers, and RCS scavengers. Limited bioavailability and bio efficacy of RCS sequesters suggest importance of nanoparticles and nanocarriers. Identification of RCS and screening of compounds ability to sequester RCS employ several bioassays and analytical techniques. Present review describes in-depth study of RCS sources, types, properties, identification techniques, therapeutic approaches, nanocarriers, and their role in various diseases. This study will give an idea for therapeutic development to combat the RCS associated chronic diseases.
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Affiliation(s)
- Shivkanya Fuloria
- Faculty of Pharmacy, AIMST University, Kedah, Bedong 08100, Malaysia;
| | - Vetriselvan Subramaniyan
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Kuala Lumpur 42610, Malaysia; (V.S.); (Y.S.W.)
| | - Sundram Karupiah
- Faculty of Pharmacy, AIMST University, Kedah, Bedong 08100, Malaysia;
| | - Usha Kumari
- Faculty of Medicine, AIMST University, Kedah, Bedong 08100, Malaysia;
| | | | | | - Yuan Seng Wu
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Kuala Lumpur 42610, Malaysia; (V.S.); (Y.S.W.)
| | - Rhanye Mac Guad
- Faculty of Medicine and Health Science, University Malaysia Sabah, Kota Kinabalu 88400, Malaysia;
| | - Kaviraja Udupa
- Department of Neurophysiology, NIMHANS, Bangalore 560029, India;
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8
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Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary Gland Hypofunction and Xerostomia in Head and Neck Radiation Patients. J Natl Cancer Inst Monogr 2020; 2019:5551361. [PMID: 31425600 DOI: 10.1093/jncimonographs/lgz016] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 05/21/2019] [Accepted: 05/26/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The most manifest long-term consequences of radiation therapy in the head and neck cancer patient are salivary gland hypofunction and a sensation of oral dryness (xerostomia). METHODS This critical review addresses the consequences of radiation injury to salivary gland tissue, the clinical management of salivary gland hypofunction and xerostomia, and current and potential strategies to prevent or reduce radiation injury to salivary gland tissue or restore the function of radiation-injured salivary gland tissue. RESULTS Salivary gland hypofunction and xerostomia have severe implications for oral functioning, maintenance of oral and general health, and quality of life. Significant progress has been made to spare salivary gland function chiefly due to advances in radiation techniques. Other strategies have also been developed, e.g., radioprotectors, identification and preservation/expansion of salivary stem cells by stimulation with cholinergic muscarinic agonists, and application of new lubricating or stimulatory agents, surgical transfer of submandibular glands, and acupuncture. CONCLUSION Many advances to manage salivary gland hypofunction and xerostomia induced by radiation therapy still only offer partial protection since they are often of short duration, lack the protective effects of saliva, or potentially have significant adverse effects. Intensity-modulated radiation therapy (IMRT), and its next step, proton therapy, have the greatest potential as a management strategy for permanently preserving salivary gland function in head and neck cancer patients.Presently, gene transfer to supplement fluid formation and stem cell transfer to increase the regenerative potential in radiation-damaged salivary glands are promising approaches for regaining function and/or regeneration of radiation-damaged salivary gland tissue.
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Affiliation(s)
- Siri Beier Jensen
- Department of Dentistry and Oral Health, Faculty of Health, Aarhus University, Aarhus, Denmark
| | - Arjan Vissink
- Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center, Groningen, The Netherlands
| | | | - Mary E Reyland
- Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO
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King M, Joseph S, Albert A, Thomas TV, Nittala MR, Woods WC, Vijayakumar S, Packianathan S. Use of Amifostine for Cytoprotection during Radiation Therapy: A Review. Oncology 2019; 98:61-80. [PMID: 31846959 DOI: 10.1159/000502979] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 08/19/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Radiation therapy is a cornerstone of the therapeutic modalities used in modern oncology. However, it is sometimes limited in its ability to achieve optimal tumor control by radiation-induced normal tissue toxicity. In delivering radiation therapy, a balance must be achieved between maximizing the dose to the tumor and minimizing any injury to the normal tissues. Amifostine was the first Food and Drug Administration (FDA)-approved clinical radiation protector intended to reduce the impact of radiation on normal tissue, lessening its toxicity and potentially allowing for increased tumor dose/control. Despite being FDA-approved almost 20 years ago, Amifostine has yet to achieve widespread clinical use. SUMMARY A thorough review of Amifostine's development, mechanism of action, and current clinical status were conducted. A brief history of Amifostine is given, from its development at Walter Reid Institute of Research to its approval for clinical use. The mechanism of action of Amifostine is explored. The results of a complete literature review of all prospective randomized trials to date involving the use of Amifostine in radiation therapy are presented. The results are arranged by treatment site and salient findings discussed. Side effects and complications to consider in using Amifostine are reviewed. Key Messages: Amifostine has been explored as a radiation protectant in most radiation treatment sites. Studies have demonstrated efficacy of Amifostine in all treatment sites reviewed, but results are heterogeneous. The heterogeneity of studies looking at Amifostine as a clinical radiation protectant has precluded a definitive answer on its efficacy. Complicating its clinical use is its toxicity and delivery requirements. Amifostine has largely fallen out of use with the advent of intensity modulated radiation therapy (IMRT). However, side effects with IMRT remain a challenge and concern. The use of Amifostine in the IMRT era has been poorly explored and is worthy of future study.
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Affiliation(s)
- Maurice King
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Sanjay Joseph
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Ashley Albert
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Toms V Thomas
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Mary R Nittala
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA,
| | - William C Woods
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Srinivasan Vijayakumar
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Satyaseelan Packianathan
- Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, Mississippi, USA
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10
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Ma SJ, Rivers CI, Serra LM, Singh AK. Long-term outcomes of interventions for radiation-induced xerostomia: A review. World J Clin Oncol 2019; 10:1-13. [PMID: 30627521 PMCID: PMC6318483 DOI: 10.5306/wjco.v10.i1.1] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 12/07/2018] [Accepted: 12/17/2018] [Indexed: 02/06/2023] Open
Abstract
Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose de-escalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.
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Affiliation(s)
- Sung Jun Ma
- University at Buffalo, The State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Charlotte I Rivers
- University at Buffalo, The State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Lucas M Serra
- University at Buffalo, The State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Anurag K Singh
- University at Buffalo, The State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
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11
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Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration. Pharm Res 2018; 35:99. [PMID: 29556791 DOI: 10.1007/s11095-018-2386-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 03/09/2018] [Indexed: 01/09/2023]
Abstract
PURPOSE Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. METHODS Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. RESULTS WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. CONCLUSIONS Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.
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Peng X, Varendi K, Maimets M, Andressoo JO, Coppes RP. Role of glial-cell-derived neurotrophic factor in salivary gland stem cell response to irradiation. Radiother Oncol 2017; 124:448-454. [PMID: 28784438 DOI: 10.1016/j.radonc.2017.07.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 07/06/2017] [Accepted: 07/06/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND PURPOSE Recently, stem cell therapy has been proposed to allow regeneration of radiation damaged salivary glands. It has been suggested that glial-cell-derived neurotrophic factor (GDNF) promotes survival of mice salivary gland stem cells (mSGSCs). The purpose of this study was to investigate the role of GDNF in the modulation of mSGSC response to irradiation and subsequent salivary gland regeneration. METHODS Salivary gland sphere derived cells of Gdnf hypermorphic (Gdnfwt/hyper) and wild type mice (Gdnfwt/wt) were irradiated (IR) with γ-rays at 0, 1, 2, 4 and 8Gy. mSGSC survival and stemness were assessed by calculating surviving fraction measured as post-IR sphere forming potential and population doublings. Flow cytometry was used to determine the CD24hi/CD29hi stem cell (SC) population. QPCR and immunofluorescence was used to detect GDNF expression. RESULTS The IR survival responses of mSGSCs were similar albeit resulted in larger spheres and an increased cell number in the Gdnfwt/hyper compared to Gdnfwt/wt group. Indeed, mSGSC of Gdnfwt/hyper mice showed high sphere forming efficiency upon replating. Interestingly, GDNF expression co-localized with receptor tyrosine kinase (RET) and was upregulated after IR in vitro and in vivo, but normalized in vivo after mSGSC transplantation. CONCLUSION GDNF does not protect mSGSCs against irradiation but seems to promote mSGSCs proliferation through the GDNF-RET signaling pathway. Post-transplantation stimulation of GDNF/RET pathway may enhance the regenerative potential of mSGSCs.
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Affiliation(s)
- Xiaohong Peng
- Departments of Cell Biology and Radiation Oncology, University Medical Centrum Groningen, University of Groningen, The Netherlands
| | - Kärt Varendi
- Institute of Biotechnology, University of Helsinki, Finland
| | - Martti Maimets
- Departments of Cell Biology and Radiation Oncology, University Medical Centrum Groningen, University of Groningen, The Netherlands; BRIC-Biotech Research and Innovation Centre, Copenhagen, Denmark
| | - Jaan-Olle Andressoo
- Institute of Biotechnology, University of Helsinki, Finland; Institute of Biosciences and Medical Technology - BioMediTech, University of Tampere, Finland
| | - Rob P Coppes
- Departments of Cell Biology and Radiation Oncology, University Medical Centrum Groningen, University of Groningen, The Netherlands.
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Riley P, Glenny A, Hua F, Worthington HV, Cochrane Oral Health Group. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev 2017; 7:CD012744. [PMID: 28759701 PMCID: PMC6483146 DOI: 10.1002/14651858.cd012744] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction. OBJECTIVES To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction. SEARCH METHODS Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin). AUTHORS' CONCLUSIONS There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.
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Affiliation(s)
- Philip Riley
- Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterCochrane Oral HealthJR Moore BuildingOxford RoadManchesterUKM13 9PL
| | - Anne‐Marie Glenny
- The University of ManchesterDivision of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and HealthJR Moore BuildingOxford RoadManchesterUKM13 9PL
| | - Fang Hua
- Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterCochrane Oral HealthJR Moore BuildingOxford RoadManchesterUKM13 9PL
| | - Helen V Worthington
- Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterCochrane Oral HealthJR Moore BuildingOxford RoadManchesterUKM13 9PL
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Doi H, Matsumoto S, Odawara S, Shikata T, Kitajima K, Tanooka M, Takada Y, Tsujimura T, Kamikonya N, Hirota S. Pravastatin reduces radiation-induced damage in normal tissues. Exp Ther Med 2017; 13:1765-1772. [PMID: 28565765 PMCID: PMC5443166 DOI: 10.3892/etm.2017.4192] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 12/23/2016] [Indexed: 12/26/2022] Open
Abstract
Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.
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Affiliation(s)
- Hiroshi Doi
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Seiji Matsumoto
- Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Soichi Odawara
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Toshiyuki Shikata
- Department of Pharmacy, Hyogo College of Medicine Sasayama Medical Center, Sasayama, Hyogo 669-2321, Japan
| | - Kazuhiro Kitajima
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Masao Tanooka
- Department of Radiological Technology, Hyogo College of Medicine College Hospital, Nishinomiya, Hyogo 663-8501, Japan
| | - Yasuhiro Takada
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Tohru Tsujimura
- Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Norihiko Kamikonya
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Shozo Hirota
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
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Wu HY, Hu ZH, Jin T. Sustained-release microspheres of amifostine for improved radio-protection, patient compliance, and reduced side effects. Drug Deliv 2016; 23:3704-3711. [PMID: 27855533 DOI: 10.1080/10717544.2016.1223222] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
A biweekly administration of sustained-release microsphere dosage form of amifostine, a radioprotective drug used in radiotherapy, was performed to examine the feasibility to minimize injection frequency and blood concentration-associated side effects. Model animal trials indicated that this subcutaneously injecting microspheres, 50-100 μm in diameter, achieved bi-weekly prolonged radio-protective efficacy and, at the same time, significantly reduced skin irritation than the solution form of amifostine given by the same administration route. In addition, the hypertension associated with blood concentration of amifostine was not observed in the drug-treated rats. The animals given the amifostine microspheres and amifostine showed significantly differences in white blood cell, red blood cell, hematocrit, hemoglobin and spleen tissue histopathology after exposed under a cobalt-60 γ-radiation at a dose rate of 1.0 Gy/min for 6 min. The in vitro release profile of amifostine from the micropsheres showed a minor initial burst (less than 20% of total drug loading in the first day of administration), consisting with the side effects observations. The results suggest that amifostine encapsulated in sustained-release microspheres may be an ideal dosage form for prolonged radio-protective efficacy and improved patient compliance.
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Affiliation(s)
- Hong-Yu Wu
- a Department of Radiation Oncology , Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , People's Republic of China and
| | - Zhen-Hua Hu
- b Pharmacy Department of Shanghai Jiaotong University , Shanghai , People's Republic of China
| | - Tuo Jin
- b Pharmacy Department of Shanghai Jiaotong University , Shanghai , People's Republic of China
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Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement. Crit Rev Oncol Hematol 2016; 102:47-54. [PMID: 27061883 DOI: 10.1016/j.critrevonc.2016.03.012] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Accepted: 03/09/2016] [Indexed: 01/28/2023] Open
Abstract
Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements).
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Swick A, Kimple RJ. Wetting the whistle: neurotropic factor improves salivary function. J Clin Invest 2014; 124:3282-4. [PMID: 25036702 DOI: 10.1172/jci77194] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Xerostomia, or dry mouth, is a common side effect of head and neck radiotherapy, Sjögren syndrome, diabetes, old age, and numerous medications. In this issue of the JCI, Xiao and colleagues identified glial cell line-derived neurotrophic factor (GDNF) as a potential stimulus for salivary stem cell growth. Due to its ability to promote neuronal growth, differentiation, and survival, GDNF is currently being used in clinical trials as a treatment for Parkinson disease; therefore, the findings of Xiao and colleagues may initiate a potential treatment for the millions of patients who suffer from xerostomia each year.
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Gu J, Zhu S, Li X, Wu H, Li Y, Hua F. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials. PLoS One 2014; 9:e95968. [PMID: 24788761 PMCID: PMC4008569 DOI: 10.1371/journal.pone.0095968] [Citation(s) in RCA: 93] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 04/01/2014] [Indexed: 01/10/2023] Open
Abstract
Background Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent. Methods By searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs) about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software. Results Seventeen trials including a total of 1167 patients (604 and 563 each arm) were analyzed in the meta-analysis. The pooled data showed that the use of amifostine significantly reduce the risk of developing Grade3–4 mucositis (relative risk [RR],0.72; 95% confidence interval [CI],0.54–0.95; p<0.00001), Grade 2–4 acute xerostomia (RR,0.70; 95%CI,0.52–0.96; p = 0.02), or late xerostomia (RR,0.60; 95%CI,0.49–0.74; p<0.00001) and Grade 3–4 dysphagia (RR,0.39; 95%CI,0.17–0.92; p = 0.03). However, subgroup analysis demonstrated that no statistically significant reduction of Grade3–4 mucositis (RR,0.97; 95% CI,0.74–1.26; p = 0.80), Grade 2–4 acute xerostomia (RR,0.35; 95%CI,0.02–5.44; p = 0.45), or late xerostomia (RR,0.40; 95%CI,0.13–1.24; p = 0.11) and Grade 3–4 dysphagia (RR,0.23; 95%CI,0.01–4.78; p = 0.35) was observed in patients treated with concomitant chemoradiotherapy. Compared with placebo or observation, amifostine does not show tumor protective effect in complete response (RR,1.02; 95%CI,0.89–1.17; p = 0.76) and partial response (RR,0.90; 95%CI, 0.56–1.44; p = 0.66). For the hematologic side effect, no statistical difference of Grade 3–4 leucopenia (RR,0.60; 95%CI,0.35–1.05; p = 0.07), anemia (RR,0.80; 95%CI, 0.42–1.53; p = 0.50) and thrombocytopenia (RR,0.43; 95%CI,0.16–1.15; p = 0.09) were found between amifostine and control groups. The most common amifostine related side effects were nausea, emesis, hypotension and allergic with an average incidence rate (Grade 3–4) of 5%, 6%, 4% and 4% respectively. Conclusion This systematic review showed that amifostine significantly reduce the serious mucositis, acute/late xerastomia and dysphagia without protection of the tumor in HNSCC patients treated with radiotherapy. And the toxicities of amifostine were generally acceptable.
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Affiliation(s)
- Jundong Gu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
- Department of Oncology, Tianjin Union Medical Center, Tianjin, China
| | - Siwei Zhu
- Department of Oncology, Tianjin Union Medical Center, Tianjin, China
| | - Xuebing Li
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hua Wu
- Department of Human resources, Tianjin Union Medical Center, Tianjin, China
| | - Yang Li
- Department of obstetrics and gynecology, Tianjin Hospital of Tianjin City, Tianjin, China
| | - Feng Hua
- Department of surgery oncology, Shandong cancer hospital, Jinan, China
- * E-mail:
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Oliai C, Yang LX. Radioprotectants to reduce the risk of radiation-induced carcinogenesis. Int J Radiat Biol 2013; 90:203-13. [PMID: 24164532 DOI: 10.3109/09553002.2014.859762] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE Development of radioprotective agents has focused primarily on cytoprotection from relatively high doses of therapeutic radiation and nuclear disasters. Epidemiological studies and radiobiological models report the potential for stochastic effects from relatively low-dose radiation exposure. Diagnostic studies like computed tomography (CT) expose the patient to a small but significant amount of radiation, which has been reported to increase the risk for carcinogenesis. Young patients expected to undergo multiple CT studies may benefit from a protective agent given prior to CT. This review includes published data of agents that have been shown to protect against radiation-induced carcinogenesis. A discussion follows regarding the data that describes the extent of radiation exposure during CT, as well as technical modifications, which also reduce radiation exposure. RESULTS/CONCLUSIONS Most experiments have used in vivo animal models or in vitro cell lines. Ethical barriers prevent large-scale human studies, although, there are two prospective human studies from the Chernobyl nuclear accident. Collectively, all of these studies provide evidence of statistically significant reductions in radiation-induced carcinogenesis. Protection is achieved by several mechanisms, which include free radical scavenging, caloric restriction, non-steroidal anti-inflammatory agents, humoral factors, and an oxidative agent. Enhanced efficacy is achieved when targeting multiple mechanisms. The data presented provides the scientific foundation for future development of a radioprotectant that may reduce the risk of carcinogenesis from low-dose exposure when certain at-risk populations undergo diagnostic studies like CT.
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Affiliation(s)
- Caspian Oliai
- Department of Radiation Oncology, California Pacific Medical Center , San Francisco, CA , USA
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Scrimger R. Salivary gland sparing in the treatment of head and neck cancer. Expert Rev Anticancer Ther 2012; 11:1437-48. [PMID: 21929317 DOI: 10.1586/era.11.101] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Radiotherapy is an important component of the multimodality treatment of head and neck cancer. Although an effective treatment for many patients, it can have significant long-term sequelae. In particular, xerostomia - or dry mouth - caused by salivary gland injury is a serious problem suffered by most patients and leads to problems with oral comfort, dental health, speech and swallowing. This article explores the mechanisms behind radiation injury to the major salivary glands, as well as different strategies to minimize and alleviate xerostomia. This includes technical approaches to minimize radiation dose to salivary tissue, such as intensity-modulated radiotherapy and surgical transfer of salivary glands, as well as pharmacologic approaches to stimulate or protect the salivary tissue. The scientific literature will be critically examined to see what works and what strategies have been less effective in attempting to minimize xerostomia in head and neck cancer patients.
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Affiliation(s)
- Rufus Scrimger
- Department of Oncology, University of Alberta, 11560 University Ave NW, Edmonton, AB, T6G 1Z2, Canada.
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Bourhis J, Blanchard P, Maillard E, Brizel DM, Movsas B, Buentzel J, Langendijk JA, Komaki R, Swan Leong S, Levendag P, Pignon JP. Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol 2011; 29:2590-7. [PMID: 21576630 DOI: 10.1200/jco.2010.33.1454] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Controversy exists regarding whether or not amifostine might reduce the efficacy of cancer treatment. The aim of this meta-analysis was to evaluate the impact of amifostine on overall survival (OS) and progression-free survival (PFS) in patients treated with radiotherapy or chemoradiotherapy. MATERIAL AND METHODS Updated data from individual patients with non-small-cell lung cancer, head and neck squamous cell carcinoma, and pelvic cancer treated with radiotherapy or chemoradiotherapy and randomly assigned to amifostine or not were included. The primary end point was OS. RESULTS Twenty-two randomized trials (2279 patients) were potentially eligible. Data were available for 16 trials (1554 patients), but four trials (435 patients) were excluded after data checking. Ultimately 12 trials and 1119 patients were analyzed. A total of 431 patients were treated with radiotherapy alone (three trials), and 688 patients were treated with chemoradiotherapy (nine trials). Thirty-three percent of patients had lung cancers, 65% had head and neck cancers, and 2% had pelvic carcinomas. Ninety-one percent of patients had locally advanced disease (early stage, 9%). Median follow-up was 5.2 years. The hazard ratio (HR) of death was 0.98 (95% CI, 0.84 to 1.14; P = .78). On the basis of 11 trials (1091 patients), the HR of progression, relapse, or death was 1.05 (95% CI, 0.90 to 1.22; P = .53). The tests for heterogeneity were not significant (P ≥ .73), and there was no significant variation of treatment effect according to sex, age, tumor site, stage, histology, locoregional treatment, or type of administration for either end point. CONCLUSION Amifostine did not reduce OS and PFS in patients treated with radiotherapy or chemoradiotherapy.
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Affiliation(s)
- Jean Bourhis
- Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France
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Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A, McCabe MG, Meyer S, Khalid T. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 2011; 2011:CD000978. [PMID: 21491378 PMCID: PMC7032547 DOI: 10.1002/14651858.cd000978.pub5] [Citation(s) in RCA: 124] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.
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Affiliation(s)
- Helen V Worthington
- Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland III Building, Oxford Road, Manchester, UK, M13 9PL
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Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A, McCabe MG, Meyer S, Khalid T. Interventions for preventing oral mucositis for patients with cancer receiving treatment. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2010. [DOI: 10.1002/14651858.cd000978.pub4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Vissink A, Mitchell JB, Baum BJ, Limesand KH, Jensen SB, Fox PC, Elting LS, Langendijk JA, Coppes RP, Reyland ME. Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers. Int J Radiat Oncol Biol Phys 2010; 78:983-91. [PMID: 20970030 PMCID: PMC2964345 DOI: 10.1016/j.ijrobp.2010.06.052] [Citation(s) in RCA: 232] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2010] [Revised: 06/12/2010] [Accepted: 06/20/2010] [Indexed: 12/22/2022]
Abstract
The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.
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Affiliation(s)
- Arjan Vissink
- Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Grongingen, The Netherlands
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Langendijk JA, Doornaert P, Rietveld DHF, Verdonck-de Leeuw IM, Leemans CR, Slotman BJ. A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol 2009; 90:189-95. [PMID: 19167120 DOI: 10.1016/j.radonc.2008.12.017] [Citation(s) in RCA: 156] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2008] [Revised: 12/30/2008] [Accepted: 12/31/2008] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Recently, we found that swallowing dysfunction after curative (chemo) radiation (CH) RT has a strong negative impact on health-related quality of life (HRQoL), even more than xerostomia. The purpose of this study was to design a predictive model for swallowing dysfunction after curative radiotherapy or chemoradiation. MATERIALS AND METHODS A prospective study was performed including 529 patients with head and neck squamous cell carcinoma (HNSCC) treated with curative (CH) RT. In all patients, acute and late radiation-induced morbidity (RTOG Acute and Late Morbidity Scoring System) was scored prospectively. To design the model univariate and multivariate logistic regression analyses were carried out with grade 2 or higher RTOG swallowing dysfunction at 6 months as the primary (SWALL(6months)) endpoint. The model was validated by comparing the predicted and observed complication rates and by testing if the model also predicted acute dysphagia and late dysphagia at later time points (12, 18 and 24 months). RESULTS After univariate and multivariate logistic regression analyses, the following factors turned out to be independent prognostic factors for SWALL(6months): T3-T4, bilateral neck irradiation, weight loss prior to radiation, oropharyngeal and nasopharyngeal tumours, accelerated radiotherapy and concomitant chemoradiation. By summation of the regression coefficients derived from the multivariate model, the Total Dysphagia Risk Score (TDRS) could be calculated. In the logistic regression model, the TDRS was significantly associated with SWALL(6months) ((p<0.001). Subsequently, we defined three risk groups based on the TDRS. The rate of SWALL(6months) was 5%, 24% and 46% in case of low-, intermediate- and high-risk patients, respectively. These observed percentages were within the 95% confidence intervals of the predicted values. The TDRS risk group classification was also significantly associated with acute dysphagia (P<0.001 at all time points) and with late swallowing dysfunction at 12, 18 and 24 months (p<0.001 at all time points). CONCLUSION The TDRS is a simple and validated measure to predict swallowing dysfunction after curative (CH) RT for HNC. This classification system enables identification of patients who may benefit from strategies aiming at prevention of swallowing dysfunction after curative (CH) RT such as preventive swallowing exercises during treatment and/or emerging IMRT techniques aiming at sparing anatomical structures that are involved in swallowing.
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Affiliation(s)
- Johannes A Langendijk
- Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
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Mell LK, Movsas B. Pharmacologic normal tissue protection in clinical radiation oncology: focus on amifostine. Expert Opin Drug Metab Toxicol 2008; 4:1341-50. [PMID: 18798703 DOI: 10.1517/17425255.4.10.1341] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Radiation toxicity is an important problem that limits treatment intensity and adversely affects patients' quality of life. Amifostine is a cytoprotector that can reduce toxicity and potentially improve the therapeutic ratio of radiotherapy. OBJECTIVE To discuss the role of amifostine in modern radiotherapy and compare and contrast with alternative approaches to reducing radiation toxicity. METHODS We conducted a literature search through Medline to identify randomized clinical trials pertaining to keyword 'amifostine'. We also consulted reviews, book chapters and selected articles regarding amifostine and normal tissue protection. RESULTS/CONCLUSION Amifostine is an effective normal tissue protector with level I evidence supporting its use in head and neck and gynecologic cancers but studies in other disease sites, although promising, are inconclusive. Further study is needed to demonstrate conclusively the benefits of wider amifostine use.
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Affiliation(s)
- Loren K Mell
- University of California San Diego, Department of Radiation Oncology, La Jolla, California, USA
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Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, Cohen GI, Emami B, Gradishar WJ, Mitchell RB, Thigpen JT, Trotti A, von Hoff D, Schuchter LM. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 2008; 27:127-45. [PMID: 19018081 DOI: 10.1200/jco.2008.17.2627] [Citation(s) in RCA: 340] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
PURPOSE To update a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer. METHODS An update committee reviewed literature published since the last guideline update in 2002. RESULTS Thirty-nine reports met the inclusion criteria: palifermin and dexrazoxane, three reports (two studies) each; amifostine, 33 reports (31 studies); and mesna, no published randomized trials identified since 2002. RECOMMENDATIONS Dexrazoxane is not recommended for routine use in breast cancer (BC) in adjuvant setting, or metastatic setting with initial doxorubicin-based chemotherapy. Consider use with metastatic BC and other malignancies, for patients who have received more than 300 mg/m(2) doxorubicin who may benefit from continued doxorubicin-containing therapy. Cardiac monitoring should continue in patients receiving doxorubicin. Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity, reduction of grade 3 to 4 neutropenia (alternative strategies are reasonable), and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer. It is not recommended for protection against thrombocytopenia, prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy, prevention of radiation therapy-associated mucositis in head and neck cancer, or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer. Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation (SCT) for hematologic malignancies with total-body irradiation (TBI) conditioning regimens, and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens. Data are insufficient to recommend use in the non-SCT setting.
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Han HS, Han JY, Yu SY, Pyo HR, Kim HY, Cho KH, Lee DH, Kim HT, Lee JS. Randomized phase 2 study of subcutaneous amifostine versus epoetin-alpha given 3 times weekly during concurrent chemotherapy and hyperfractionated radiotherapy for limited-disease small cell lung cancer. Cancer 2008; 113:1623-31. [PMID: 18671241 DOI: 10.1002/cncr.23790] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND The purpose of the current study was to investigate the role of amifostine and epoetin-alpha in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC). METHODS Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-alpha at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply. RESULTS Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-alpha (P = .059). Epoetin-alpha treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-alpha arm; P = .447). CONCLUSIONS Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-alpha was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated.
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Affiliation(s)
- Hye-Suk Han
- Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
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The effect of amifostine or IMRT to preserve the parotid function after radiotherapy of the head and neck region measured by quantitative salivary gland scintigraphy. Radiother Oncol 2008; 89:71-80. [PMID: 18707782 DOI: 10.1016/j.radonc.2008.07.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2008] [Revised: 06/22/2008] [Accepted: 07/16/2008] [Indexed: 11/23/2022]
Abstract
PURPOSE In this retrospective study, two approaches to preserve the parotid function after radiotherapy (RT) were compared: application of the radioprotective agent amifostine during RT and parotid-sparing intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS Patients were qualified for this analysis if (1) both parotid glands received a radiation dose of >or=50Gy using conventional radiotherapy techniques (cRT) or if they received a parotid-sparing IMRT as alternative, if (2) salivary gland scintigraphies before and after RT were performed, and if (3) a normal parotid function was present before RT. Quantitative salivary gland scintigraphy was used to assess the parotid gland function. RESULTS Altogether 275 salivary gland scintigraphies of 100 patients were analyzed. The mean relative tracer uptake (DeltaU) of patients treated with cRT, cRT with amifostine and IMRT 1-12 months after RT was 0.59 (95%CI 0.54-0.65), 0.67 (95%CI 0.59-0.76), and 0.93 (95%CI 0.78-1.07), respectively. The mean relative DeltaU 13-47 months after RT was 0.40 (95%CI 0.32-0.49), 0.60 (95%CI 0.48-0.71), and 0.92 (95%CI 0.56-1.28). At 1-12 months after RT, ANOVA testing with post-hoc comparison using the Bonferroni correction showed a significant difference between IMRT and cRT (p<0.001) or IMRT and amifostine (p<0.01). The difference between amifostine and cRT was not significant during the first year. At 13-47 months after RT, the difference between cRT and amifostine was significant (p=0.02). CONCLUSION Our data suggest that both amifostine and IMRT are able to partially preserve the parotid function after radiotherapy. The effect of IMRT appeared to be much greater.
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Multidisciplinary Management of Locally Advanced SCCHN: Optimizing Treatment Outcomes. Oncologist 2008; 13:899-910. [DOI: 10.1634/theoncologist.2007-0157] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Stevens–Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy. Radiother Oncol 2008; 87:300-3. [DOI: 10.1016/j.radonc.2008.01.021] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2007] [Revised: 01/07/2008] [Accepted: 01/21/2008] [Indexed: 11/18/2022]
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Langendijk JA, Bourhis J. Reirradiation in squamous cell head and neck cancer: recent developments and future directions. Curr Opin Oncol 2007; 19:202-9. [PMID: 17414637 DOI: 10.1097/cco.0b013e3280f00ff8] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW The purpose of this review is to highlight the most important developments in the management of recurrent or second primary head and neck carcinoma in previously irradiated areas by reirradiation that have been published in the medical literature in the past year. RECENT FINDINGS Recent research indicates that long-term survival can be achieved in a proportion of patients using more advanced chemo-reirradiation protocols in the primary as well as in postoperative reirradiation setting. Despite the promising results with regard to locoregional tumour control and survival, treatment-related acute and late morbidity remains of major concern. SUMMARY As an increasing number of patients currently receive more effective initial treatment regimens, recurrent and second primary tumours in previously irradiated areas nowadays may represent a more radio-resistant population than reported in previous studies. Therefore, full-dose chemo-reirradiation should only be applied in well selected cases.
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Affiliation(s)
- Johannes A Langendijk
- Department of Radiation Oncology, University Medical Center Groningen/University of Groningen, Groningen, The Netherlands.
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