Feasibility of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) in cirrhotic or liver transplant patients: experience in a cohort of advanced hepatocellular carcinoma patients

Invest New Drugs. 2012 Feb;30(1):376-81. doi: 10.1007/s10637-010-9525-0. Epub 2010 Aug 27.

Abstract

Purpose: The only drug that improves survival in hepatocellular carcinoma is sorafenib. FOLFOX-4 regimen is safe and widely used in patients with colorectal cancer, yielding interesting results with little toxicity. We conducted a retrospective study to evaluate the safety and the effectiveness of FOLFOX-4 in cirrhotic or liver transplanted patients with hepatocellular carcinoma ineligible for sorafenib.

Methods: Thirty seven patients were enrolled in the study. The medical record of either cirrhotic patients or liver transplanted patients with advanced hepatocellular carcinoma receiving FOLFOX-4 regimen between November 1999 and March 2006 were retrospectively analyzed. Patients received oxaliplatin 85 mg/m(2) as a 2-hour infusion on day one, and leucovorin 200 mg/m(2) as a 2-hour infusion followed by bolus 5-fluorouracil 400 mg/m(2) and a 48-hours infusion of 5-fluorouracil 2400 mg/m(2). Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred.

Results: Patients had a Child-Pugh class A (n = 16), class B cirrhosis (n = 10) or a liver transplant (n = 11) and received 2 to 37 cycles of chemotherapy (total of 310 cycles). Two (5.4%) cirrhotic patients developed neutropenic sepsis and one (2.7%) toxic death occurred. At first assessment, five patients from Child-Pugh class A (33%) and two from Child-Pugh class B group (20%) achieved a radiological response and/or alpha foeto-protein decrease, and no patient achieved a complete response.

Conclusions: In conclusion, with a manageable toxicity profile in cirrhotic Child-Pugh class A-B or liver transplanted patients, the FOLFOX-4 regimen appears to be a feasible treatment option for patients with advanced hepatocellular carcinoma unfit for sorafenib. These data need to be confirmed in a prospective study.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / mortality
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / etiology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Liver Transplantation* / adverse effects
  • Liver Transplantation* / mortality
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Paris
  • Retrospective Studies
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol