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Lu X, Zhu Q, Cai J, Yang Z, Gu G, Pang L, Su M, Zhang F, Lin H, Wu W, Xu L, Liu C. Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation. Cancer Immunol Immunother 2024; 74:18. [PMID: 39527136 PMCID: PMC11554970 DOI: 10.1007/s00262-024-03853-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 10/01/2024] [Indexed: 11/16/2024]
Abstract
Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We retrospective analyzed 159 HCC patients who underwent LT at our institution from June 2019 to December 2023, and 39 recipients (39/159, 24.5%) received pretransplant ICI therapy. The perioperative acute rejection rate and rejection-related mortality rate in the ICI group were 23.1% (9/39) and 12.8% (5/39), respectively, which were significantly higher than those in the non-ICI group, at 5% (6/120, P = 0.002) and 0% (0/120, P = 0.001). There was no significant difference in the 90-day post-transplant overall survival (OS) (P = 0.447) and recurrence-free survival (RFS) (P = 0.723) between these two groups. We found 37.1% (59/159) recipients were found to have microvascular invasion (MVI), no matter whether the HCC tumor is within Milan criteria or not. Notably, though MVI was identified as a risk factor for the LT recipients, pretransplant ICI exposure appeared to be a protective factor for HCC patients with MVI which benefits its overall survival. Besides, the RFS and OS in the ICI exposure recipients with MVI were comparable to the non-ICI exposure recipients without MVI. However, no synergistic anti-tumor effects were observed with pretransplant ICI immunotherapy when combined with locoregional of TACE, HAIC, RFA and systematic of lenvatinib or sorafenib downstaging treatments, nor with post-transplant adjuvant of systematic or FOLFOX chemotherapy. Further comprehensive studies are needed to balance the dual natural effects of immunotherapy by optimizing downstaging protocols and patient selection to reduce acute rejection and improve long-term survival.
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Affiliation(s)
- Xinjun Lu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Qi Zhu
- Department of Pancreatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Junfeng Cai
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zuozhong Yang
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Guangxiang Gu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Li Pang
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Mingye Su
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Fapeng Zhang
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Haoming Lin
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Wenrui Wu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Leibo Xu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Chao Liu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
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Ningarhari M, Bertez M, Ploquin A, Bertrand N, Desauw C, Cattan S, Catala P, Vandamme H, Cheymol C, Truant S, Lassailly G, Louvet A, Mathurin P, Dharancy S, Turpin A. Conventional cytotoxic chemotherapy for gastrointestinal cancer in patients with cirrhosis: A multicentre case-control study. Liver Int 2024; 44:682-690. [PMID: 38031969 DOI: 10.1111/liv.15813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 11/08/2023] [Accepted: 11/23/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND & AIMS Progresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver-related events associated with the use of chemotherapy in these patients. METHODS Forty-nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD-10 codes K70-K74, and matched 1:2 to non-cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver-related events and survival rate were compared. RESULTS Patients with cirrhosis (Child-Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child-Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver-related versus 0% in matched controls. WHO-PS stage > 1 (HR 3.74, CI95%: 2.13-6.57, p < .001), TNM-stage M1 (HR 3.61, CI 95%: 1.82-7.16, p < .001), non-colorectal cancer (HR 1.73, CI 95%: 1.05-2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39-3.70, p < .001) were independent prognostic factors of 2-year mortality, whereas cirrhosis was not. CONCLUSIONS Chemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes.
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Affiliation(s)
- Massih Ningarhari
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Marlène Bertez
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Anne Ploquin
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Nicolas Bertrand
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Christophe Desauw
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Stéphane Cattan
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Pascale Catala
- Centre Hospitalier de Béthune, Hépato-Gastro-Entérologie, Beuvry, France
| | - Hélène Vandamme
- Centre Hospitalier de Béthune, Hépato-Gastro-Entérologie, Beuvry, France
| | - Claire Cheymol
- GHICL Hôpital Saint-Vincent, Oncologie Médicale, Lille, France
| | - Stéphanie Truant
- CHU Lille, Hôpital Huriez, Chirurgie Digestive et Transplantation, Lille, France
| | | | - Alexandre Louvet
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Philippe Mathurin
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Sébastien Dharancy
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Anthony Turpin
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
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Oranratnachai S, Rattanasiri S, Sirachainan E, Tansawet A, Raunroadroong N, McKay GJ, Attia J, Thakkinstian A. Treatment outcomes of advanced hepatocellular carcinoma in real-life practice: Chemotherapy versus multikinase inhibitors. Cancer Med 2022; 12:3046-3053. [PMID: 36082831 PMCID: PMC9939209 DOI: 10.1002/cam4.5224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/24/2022] [Accepted: 08/23/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first-line treatment for aHCC in real-life practice. METHODS A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013-2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight-adjusted-censoring inverse-probability-weighted regression adjustment; overall survival (OS) and progression-free survival (PFS) were estimated. RESULTS A total of 504 patients were included, (Sorafenib [n = 382] and FOLFOX [n = 122]). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of -3.16 (-6.21, -0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of -2.13 (-3.03, -1.24) months, p < 0.001, was reported. CONCLUSION Despite significantly shorter median OS and PFS than Sorafenib, FOLFOX still extended OS by 8.22 months. This evidence may offer clinical utility to physicians considering treatment options for aHCC in low resource settings.
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Affiliation(s)
- Songporn Oranratnachai
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand,Oncology Clinic, Sriphat Medical Center, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
| | - Sasivimol Rattanasiri
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Ekaphop Sirachainan
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Amarit Tansawet
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand,Department of Surgery, Faculty of Medicine Vajira HospitalNavamindradhiraj UniversityBangkokThailand
| | | | - Gareth J. McKay
- Centre for Public Health, School of Medicine, Dentistry and Biomedical SciencesQueen's University BelfastBelfastUK
| | - John Attia
- Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Hunter Medical Research InstituteUniversity of NewcastleNew LambtonNew South WalesAustralia
| | - Ammarin Thakkinstian
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
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Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin in Hepatocellular Cancer with Extrahepatic Spread. J Vasc Interv Radiol 2019; 30:349-357.e2. [PMID: 30819477 DOI: 10.1016/j.jvir.2018.09.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 08/30/2018] [Accepted: 09/05/2018] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To compare treatment with hepatic arterial infusion of chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) with both extrahepatic spread (EHS) and intrahepatic tumor and patients with intrahepatic tumor only. MATERIALS AND METHODS This single-center retrospective study comprised 116 patients with advanced HCC with both intrahepatic tumor and EHS (EHS group; n = 50) or with intrahepatic tumor only (non-EHS group; n = 66) treated with HAIC including oxaliplatin, fluorouracil, and leucovorin between June 2014 and July 2016. Overall survival (OS) and radiologic responses to treatment were determined and compared between the 2 groups. RESULTS Both the objective response rate and the clinical benefit rate were higher in the non-EHS group than in the EHS group (37.9% vs 16% objective response rate, P = .010; 81.8% vs 62% clinical benefit rate, P = .017). Median OS was not statistically different between the 2 groups (14.8 months vs 9.8 months, P = .068). Subgroup analysis of OS found that patients with lung metastases survived for a shorter time (OS 7 months) than patients with other metastatic sites (P = .003) and patients free of metastases (P = .001). CONCLUSIONS HAIC is a potential treatment option for advanced HCC with limited extrahepatic metastases in a population with hepatitis B virus infection.
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DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report. Pharmaceutics 2019; 11:pharmaceutics11050199. [PMID: 31052357 PMCID: PMC6572291 DOI: 10.3390/pharmaceutics11050199] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 04/19/2019] [Accepted: 04/23/2019] [Indexed: 12/13/2022] Open
Abstract
5-Fluorouracil remains a foundational component of chemotherapy for solid tumour malignancies. While considered a generally safe and effective chemotherapeutic, 5-fluorouracil has demonstrated severe adverse event rates of up to 30%. Understanding the pharmacokinetics of 5-fluorouracil can improve the precision medicine approaches to this therapy. A single enzyme, dihydropyrimidine dehydrogenase (DPD), mediates 80% of 5-fluorouracil elimination, through hepatic metabolism. Importantly, it has been known for over 30-years that adverse events during 5-fluorouracil therapy are linked to high systemic exposure, and to those patients who exhibit DPD deficiency. To date, pre-treatment screening for DPD deficiency in patients with planned 5-fluorouracil-based therapy is not a standard of care. Here we provide a focused review of 5-fluorouracil metabolism, and the efforts to improve predictive dosing through screening for DPD deficiency. We also outline the history of key discoveries relating to DPD deficiency and include relevant information on the potential benefit of therapeutic drug monitoring of 5-fluorouracil. Finally, we present a brief case report that highlights a limitation of pharmacogenetics, where we carried out therapeutic drug monitoring of 5-fluorouracil in an orthotopic liver transplant recipient. This case supports the development of robust multimodality precision medicine services, capable of accommodating complex clinical dilemmas.
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Ravaioli M, Cucchetti A, Pinna AD, De Pace V, Neri F, Barbera MA, Maroni L, Frega G, Palloni A, De Lorenzo S, Ripoli MC, Pantaleo MA, Cescon M, Del Gaudio M, Brandi G. The role of metronomic capecitabine for treatment of recurrent hepatocellular carcinoma after liver transplantation. Sci Rep 2017; 7:11305. [PMID: 28900245 PMCID: PMC5595852 DOI: 10.1038/s41598-017-11810-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 08/14/2017] [Indexed: 12/17/2022] Open
Abstract
The management of recurrent hepatocellular carcinoma untreatable with surgical options is based on systemic therapy with sorafenib. Due to the high rates of adverse events connected to the therapy with sorafenib, metronomic capecitabine seems a promising strategy for these patients. We analyzed the data of 38 patients with hepatocellular carcinoma recurrent after liver transplantation performed at our center. We compared the outcome of 17 patients receiving metronomic capecitabine versus 20 patients experiencing best supportive care and versus the data of the literature about treatment with sorafenib. In the group treated with metronomic capecitabine we observed an increased survival after tumor recurrence at the univariate and multivariate analysis compared to the group of best supportive care (median 22 months vs. 7 months, p < 0.01). Data from the literature on the use of sorafenib showed outcomes like our study group, with similar patient and tumoral features. The episodes of acute rejection and the tumor stage at the recurrence showed a correlation with patient survival at the univariate analysis. The metronomic capecitabine for hepatocellular cancer recurrent after liver transplantation seems effective without important adverse events and comparable results to sorafenib.
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Affiliation(s)
- Matteo Ravaioli
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy.
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Antonio Daniele Pinna
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Vanessa De Pace
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Flavia Neri
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Maria Aurelia Barbera
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Alma Mater Studiorum, Bologna University, V. Massarenti 9, 40138, Bologna, Italy
| | - Lorenzo Maroni
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Giorgio Frega
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Alma Mater Studiorum, Bologna University, V. Massarenti 9, 40138, Bologna, Italy
| | - Andrea Palloni
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Alma Mater Studiorum, Bologna University, V. Massarenti 9, 40138, Bologna, Italy
| | - Stefania De Lorenzo
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Alma Mater Studiorum, Bologna University, V. Massarenti 9, 40138, Bologna, Italy
| | - Maria Cristina Ripoli
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Maria Abbondanza Pantaleo
- "G. Prodi" Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Massimo Del Gaudio
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, V. Massarenti 9, 40138, Bologna, Italy
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Alma Mater Studiorum, Bologna University, V. Massarenti 9, 40138, Bologna, Italy
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Ma JL, Zeng S, Zhang Y, Deng GL, Shen H. Epithelial-mesenchymal transition plays a critical role in drug resistance of hepatocellular carcinoma cells to oxaliplatin. Tumour Biol 2015; 37:6177-84. [PMID: 26614432 DOI: 10.1007/s13277-015-4458-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 11/17/2015] [Indexed: 01/08/2023] Open
Abstract
Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial-mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.
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Affiliation(s)
- Jun Li Ma
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008
| | - Yan Zhang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008
| | - Gan Lu Deng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008
| | - Hong Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.
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Goldstein R, Yu D, Gillmore R, Thirlwell C, O'Donoghue P, Mayer A, Meyer T. Oxaliplatin/5-fluorouracil in advanced hepatocellular carcinoma: case report and single-center retrospective review. Future Oncol 2014; 10:2007-14. [PMID: 25209630 DOI: 10.2217/fon.14.108] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
AIMS Sorafenib is the only standard therapy for advanced hepatocellular carcinoma, but has a low response rate. Leucovorin and oxaliplatin (FOLFOX) has a superior response rate versus doxorubicin among Asian sorafenib-naive patients. We aimed to retrospectively review the outcome of 20 consecutive patients treated with FOLFOX at a single European center. MATERIALS & METHODS Patients had symptomatic disease burdens unlikely to regress with sorafenib or had no proven treatment options (sorafenib-refractory or recurrence post liver transplantation). RESULTS One sorafenib-refractory patient had a complete response and two liver transplant patients experienced partial responses. Median overall survival was 6.3 months. There was one chemotherapy death due to neutropenic sepsis. CONCLUSION In advanced hepatocellular carcinoma, FOLFOX can induce clinically relevant responses, but needs prospective validation.
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Affiliation(s)
- Robert Goldstein
- UCL Cancer Institute, University College London, Gower Street, London, WC1E 6BT, UK
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Oxaliplatin-based chemotherapy: a new option in advanced hepatocellular carcinoma. a systematic review and pooled analysis. Clin Oncol (R Coll Radiol) 2014; 26:488-96. [PMID: 24856442 DOI: 10.1016/j.clon.2014.04.031] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 02/17/2014] [Accepted: 03/18/2014] [Indexed: 12/13/2022]
Abstract
Advanced hepatocellular carcinoma (HCC), for which locoregional treatment is not an option, is a candidate for palliative systemic therapy, but an accepted chemotherapy regimen does not exist. We have conducted a systematic literature review and meta-analyses to quantify the benefits of oxaliplatin (OXA)-based chemotherapy in advanced HCC in patients not exposed to sorafenib. Studies that enrolled advanced HCC patients treated with first-line OXA-based chemotherapy were identified using PubMed, Web of Science, SCOPUS, The Cochrane Register of Controlled Trials and EMBASE. A systematic review was conducted to calculate the pooled response rate and 95% confidence interval. The pooled median progression-free survival (PFS) and overall survival, weighted on the number of patients of each selected trials, were also calculated. We tested for significant heterogeneity by Cochran's chi-squared test and I-square index. Thirteen studies were included in this review, with a total of 800 patients analysed. The pooled response rate was 16.8%. The median PFS and overall survival were 4.2 and 9.3 months, respectively, with a 1 year overall survival of 37%. The weighted median PFS/overall survival and response rate were 4.5/11 months and 20% in Western patients. Conversely, in Asiatic studies, the median PFS/overall survival and response rate were 2.43/6.47 months and 13.2%, respectively. OXA-based chemotherapy is effective in advanced HCC and represents a viable option in these patients. A head to head comparison with sorafenib or a second-line agent should be verified in prospective trials.
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He SL, Shen J, Sun XJ, Zhu XJ, Liu LM, Dong JC. Efficacy of capecitabine and oxaliplatin regimen for extrahepatic metastasis of hepatocellular carcinoma following local treatments. World J Gastroenterol 2013; 19:4552-4558. [PMID: 23901232 PMCID: PMC3725381 DOI: 10.3748/wjg.v19.i28.4552] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2013] [Revised: 04/25/2013] [Accepted: 06/04/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC).
METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined by P≤ 0.05.
RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, hand-foot syndrome and fatigue.
CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.
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Colorectal cancer surgery in portal hypertensive patients: does adjuvant oxaliplatin affect prognosis? Dis Colon Rectum 2013; 56:577-85. [PMID: 23575396 DOI: 10.1097/dcr.0b013e318286f8fc] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Oxaliplatin is used in adjuvant treatment of colorectal cancer and is associated with sinusoidal obstruction syndrome. Few data are available on its effects in patients in whom portal hypertension was diagnosed before cancer treatment. OBJECTIVE Our aim was to investigate short- and long-term outcomes of surgery for colorectal cancer in patients with portal hypertension with or without cirrhosis, particularly regarding effects of adjuvant chemotherapy with oxaliplatin. DESIGN AND SETTING This was a prospective cohort study performed at an academic medical center. PATIENTS Patients with stage II or III colorectal cancer and portal hypertension who underwent curative resection were included. INTERVENTION All patients received adjuvant chemotherapy with oxaliplatin (FOLFOX 4) or 5-fluorouracil and leucovorin. MAIN OUTCOME MEASURES Potential predictive laboratory and clinical variables and postoperative (30-day) and long-term morbidity and mortality were recorded. RESULTS Of 63 patients enrolled, 23 (37%) had a total of 82 postoperative complications; 5 patients (8%) died within 30 days postoperatively. Univariate analysis showed that severe portal hypertension, preoperative Child class B, low albumin, the presence of ascites, preoperative upper GI tract bleeding, and high intraoperative blood loss were linked to postoperative morbidity. Presence of postoperative infection (p = 0.004), presence of preoperative ascites (p = 0.01), high intraoperative blood loss (p = 0.02), and preoperative upper GI tract bleeding (p = 0.03) were significantly related to mortality. Of 58 patients receiving adjuvant chemotherapy, 20 received the oxaliplatin regimen and 38 received 5-fluorouracil/leucovorin without oxaliplatin. The median length of follow-up was 26 (range, 6-36) months. Kaplan-Meier analyses showed that patients who received oxaliplatin had higher cumulative incidences of newly developed esophageal varices (p = 0.002), GI tract bleeding (p = 0.02), and newly formed ascites (p = 0.03). Death occurred in 8 of 20 patients (40%) in the oxaliplatin group and in 5 of 38 patients (13%) in the 5-fluorouracil group. Kaplan-Meier estimates of mean survival time were 34.4 months (95% CI, 32.4-36.5) in the 5-fluorouracil/leucovorin group vs 29.9 months (95% CI, 26-33.7) in the oxaliplatin group, and patients receiving oxaliplatin had a significantly higher relative risk of death (HR = 2.98; 95% CI, 1.03-8.65). Cancer-specific mortality was not related to treatment type. LIMITATIONS The study was limited by the relatively small sample size and lack of randomization, which may have led to selection bias in treatment regimens. CONCLUSIONS Colorectal cancer surgery can be done safely in portal hypertensive patients with good hepatic function; however, higher mortality is expected in patients with compromised hepatic function reserve. Compared with adjuvant chemotherapy without oxaliplatin, oxaliplatin-based chemotherapy does not significantly reduce cancer-specific mortality and may increase overall morbidity and mortality. Therefore, oxaliplatin-based chemotherapy should be used with caution in patients who have portal hypertension, even in those with good liver function.
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Dhooge M, Coriat R, Mir O, Perkins G, Brezault C, Boudou-Rouquette P, Goldwasser F, Chaussade S. Feasibility of Gemcitabine plus Oxaliplatin in Advanced Hepatocellular Carcinoma Patients with Child-Pugh B Cirrhosis. Oncology 2013; 84:32-8. [DOI: 10.1159/000342763] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Accepted: 08/15/2012] [Indexed: 12/11/2022]
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LoConte NK, Holen KD, Schelman WR, Mulkerin DL, Deming DA, Hernan HR, Traynor AM, Goggins T, Groteluschen D, Oettel K, Robinson E, Lubner SJ. A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study. Invest New Drugs 2012; 31:943-8. [PMID: 23263993 DOI: 10.1007/s10637-012-9916-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 12/12/2012] [Indexed: 12/11/2022]
Abstract
Chemotherapy has yielded minimal clinical benefit in pancreatic and biliary tract cancer. A high-dose, short course capecitabine schedule with oxaliplatin, has shown some efficacy with a lower incidence of palmar-plantar erythrodysesthesia. Achieving high exposures of the targeted agent sorafenib may be possible with this shorter schedule of capecitabine by avoiding dermatologic toxicity. All patients had pancreatic or biliary tract cancer. Patients in both cohorts received oxaliplatin 85 mg/m2 followed by capecitabine 2,250 mg/m2 PO every 8 h x 6 doses starting on days 1 and 15 of a 28 day cycle, or 2DOC (2 Day Oxaliplatin/Capecitabine). Cohort 1 used sorafenib 200 mg BID, and cohort 2 used sorafenib 400 mg BID. Sixteen patients were enrolled. Across all cycles the most common grade 1 or 2 adverse events were fatigue (10 pts), diarrhea (10 pts), nausea (9 pts), vomiting (8 pts), sensory neuropathy (8 pts), thrombocytopenia (7 pts), neutropenia (5 pts), and hand-foot syndrome (5 pts). Grade 3 toxicites included neutropenia, mucositis, fatigue, vomiting and diarrhea. Cohort 1 represented the MTD. Two partial responses were seen, one each in pancreatic and biliary tract cancers. The recommended phase II dose of sorafenib in combination with 2DOC is 200 mg BID. There were infrequent grade 3 toxicities, most evident with sorafenib at 400 mg BID.
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Affiliation(s)
- Noelle K LoConte
- University of Wisconsin Carbone Cancer Center and the University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, K6/548 CSC, Madison, WI 53792, USA.
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Brito AF, Abrantes AM, Pinto-Costa C, Gomes AR, Mamede AC, Casalta-Lopes J, Gonçalves AC, Sarmento-Ribeiro AB, Tralhão JG, Botelho MF. Hepatocellular carcinoma and chemotherapy: the role of p53. Chemotherapy 2012; 58:381-6. [PMID: 23257706 DOI: 10.1159/000343656] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2012] [Accepted: 09/19/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver. A major proportion of HCCs also present mutation of the gene that encodes p53, which confers chemoresistance. The main goal of this work is to investigate the effect of cisplatin, doxorubicin and 5-fluoruracil (5-FU) in three human HCC cell lines which differ in p53 expression. METHODS HepG2 (expressing normal p53), HuH7 (expressing mutated p53) and Hep3B2.1-7 (not expressing p53) cell lines were cultivated in the presence of cisplatin, doxorubicin and 5-FU. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay). The type of cell death and Bax and Bcl2 activation were assessed by flow cytometry. RESULTS It was found that for all of the cell lines studied, the agent that gave the most satisfactory results was doxorubicin. 5-FU demonstrated no activity in these cell lines. CONCLUSIONS For all the cell lines studied, doxorubicin was the most satisfactory agent. In HepG2 and HuH7 cell lines, it can activate Bax with statistical significance.
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Affiliation(s)
- A F Brito
- Biophysics Unit, IBILI - Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
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Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2. Anticancer Drugs 2012; 23:739-44. [PMID: 22700002 DOI: 10.1097/cad.0b013e3283556b9b] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.
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Abstract
The positive results of sorafenib have unveiled a new direction of research in the management of hepatocellular carcinoma (HCC). Since then intensive efforts have been focused on development of novel management strategy to further improve the outcome for patients with HCC. Emerging data have suggested that tumor progression of HCC is driven by a number of deregulated signaling pathways and/or epigenetic mechanism. Thus much effort is dedicated to identification of novel agents targeting these dysregulated pathways. Combinations of targeted therapeutics and transarterial chemoembolization (TACE), or different systemic therapeutics also hold the promise to improve treatment outcome beyond sorafenib. This review aims to summarize the current status of clinical development of treatment in HCC. Perspectives on future direction of research will also be discussed.
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Abstract
The positive results of sorafenib have unveiled a new direction of research in the management of hepatocellular carcinoma (HCC). Since then intensive efforts have been focused on development of novel management strategy to further improve the outcome for patients with HCC. Emerging data have suggested that tumor progression of HCC is driven by a number of deregulated signaling pathways and/or epigenetic mechanism. Thus much effort is dedicated to identification of novel agents targeting these dysregulated pathways. Combinations of targeted therapeutics and transarterial chemoembolization (TACE), or different systemic therapeutics also hold the promise to improve treatment outcome beyond sorafenib. This review aims to summarize the current status of clinical development of treatment in HCC. Perspectives on future direction of research will also be discussed.
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Mir O, Coriat R, Boudou-Rouquette P, Ropert S, Durand JP, Cessot A, Mallet V, Sogni P, Chaussade S, Pol S, Goldwasser F. Gemcitabine and oxaliplatin as second-line treatment in patients with hepatocellular carcinoma pre-treated with sorafenib. Med Oncol 2012; 29:2793-9. [PMID: 22427209 DOI: 10.1007/s12032-012-0208-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2012] [Accepted: 03/02/2012] [Indexed: 12/12/2022]
Abstract
Some patients with advanced hepatocellular carcinoma (HCC) progressing under sorafenib remain eligible for further systemic therapy. Little is known on the feasibility of systemic treatment beyond sorafenib in this setting. Consecutive HCC patients pre-treated with sorafenib received gemcitabine 1,000 mg/m² and oxaliplatin 100 mg/m² every 14 days. Exclusion criteria included Child C cirrhosis, PS≥3, creatinine clearance<20 ml/min, albumin<25 g/L and bilirubin>54 μmol/L. Pre-treatment body composition was evaluated by CT scan to detect muscle wasting (sarcopenia). The primary evaluation criterion was safety. Secondary evaluation criteria were response rate, and progression-free (PFS) and overall survival (OS). Eighteen patients (median age: 64 years, range 25-77) received a total of 90 cycles (median per patient: 4, range 1-16). Eight patients (44.4 %) had a PS of 2, 5 (27.8%) had Child-Pugh B cirrhosis and 13 (72.2%) had a CLIP score>3. The most frequent toxicities were thrombocytopenia (grade 2-4: n=7, 38.9%) and peripheral neuropathy (grade 2-3: n=7, 38.9%). The overall response rate was 18.8% (95% CI: 0-37.9), and another 18.8 % of patients had stable disease. The median PFS and OS were 3.2 (95% CI: 2.3-3.9) and 4.7 (95% CI: 3.8-8.1) months, respectively. Overall survival was significantly longer in patients without sarcopenia [10.0 months (95% CI: 7.0-13.8) vs. 3.0 months (95 % CI: 2.5-3.9), p<0.001] and in patients with an ECOG PS<2 [8.1 months (95% CI: 7.0-13.8) vs. 3.8 months (95% CI: 2.5-3.9), p=0.017]. In our experience, gemcitabine-oxaliplatin was feasible and had detectable clinical activity in HCC patients pre-treated with sorafenib. Further studies are needed to confirm these findings.
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Affiliation(s)
- Olivier Mir
- Department of Medical Oncology, Centre for Research on Angiogenesis Inhibitors (CERIA), Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, 27, rue du faubourg Saint Jacques, 75014, Paris, France.
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Cabibbo G, Palmeri L, Palmeri S, Craxì A. Should cirrhosis change our attitude towards treating non-hepatic cancer? Liver Int 2012; 32:21-7. [PMID: 22098398 DOI: 10.1111/j.1478-3231.2011.02629.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2010] [Accepted: 07/28/2011] [Indexed: 12/17/2022]
Abstract
Cirrhosis is a major cause of morbidity and mortality and is the end stage of any chronic liver disease. Cancer, a leading cause of death worldwide, is a growing global health issue. There are limited data in the literature on the incidence, prevalence and management of non-hepatic cancers (NHC) in cirrhotic patients. The aim of this brief review was to underline the main concerns, pitfalls and warnings regarding practice for these patients. Survival of patients with compensated cirrhosis is significantly longer than that of decompensated cirrhosis and patients with NHC and in Child-Pugh class C should not be candidates for cytotoxic chemotherapy. It is important before starting cytotoxic chemotherapy to assess the aetiology and stage of liver disease and to screen these patients for portal hypertension and fluid retention. During cytotoxic chemotherapy, the effectiveness of cancer treatment, as well the appearance of early signs of hepatic decompensation, must be thoroughly monitored. Future phase 3 trial designs in oncology should include a share of patients with compensated cirrhosis to obtain specific information in this setting. Identification of tests able to measure the global degree of hepatic impairment caused by cirrhosis could help in the management of this particular clinical situation.
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Affiliation(s)
- Giuseppe Cabibbo
- Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
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Zhang Q, Chen H, Li Q, Zang Y, Chen X, Zou W, Wang L, Shen ZY. Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study. Invest New Drugs 2011; 29:1360-9. [PMID: 21809025 DOI: 10.1007/s10637-011-9726-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2011] [Accepted: 07/21/2011] [Indexed: 12/15/2022]
Abstract
The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m(2) on day 1, leucovorin (calcium folinate, CF) 200 mg/m(2) on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m(2) as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57 months by combination chemotherapy. The 1- and 3-year survival rates were 89.7% and 79.3% with chemotherapy versus 69.0% and 62.1% without chemotherapy. The cumulative 1-year survival was significantly increased by chemotherapy (log-rank test, P = 0.043). The 6-month tumor-free survival rate was 24.1% higher with chemotherapy than without. The recurrence rate after LT was significantly different between the two groups at 6 months (P = 0.036), but not at 3 years (P = 0.102). The chemotherapy regimen was generally well tolerated. Post-LT adjuvant chemotherapy with oxaliplatin/5-FU/CF could not prevent tumor recurrence post-LT but may contribute to improve the survival of HCC patients who do not meet the Milan criteria. These results should be verified in a larger sample with a longer follow-up period.
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Affiliation(s)
- Qing Zhang
- Institute of Liver Transplantation, General Hospital of Chinese People's Armed Police Force, 69 Yongding Road, Haidian District, Beijing, 100039, China
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