title: Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma after failure of anti-angiogenic therapies.
abstract: BACKGROUND
  Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy.
  
  
  METHODS
  We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy.
  
  
  RESULTS
  We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period. Grade 3/4 toxicity was observed in 25 % of patients, mainly neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of patients respectively. Grade <3 toxicity was mainly hematological and neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial response was observed in 20 % of patients, while 46 % had stable disease. Median OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months. Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors were prognostic for PFS or tumor response.
  
  
  CONCLUSIONS
  The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment. The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients. These results would merit confirmation in a prospective randomized study.
authors.affiliation: Department of Oncologic Medicine, Gustave-Roussy, Villejuif, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Patrikidou
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sinapi
authors.forename: Hélène
authors.initials: H
authors.lastname: Regnault
authors.forename: Florence
authors.initials: F
authors.lastname: Fayard
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouattour
authors.forename: Laetitia
authors.initials: L
authors.lastname: Fartoux
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: Valerie
authors.initials: V
authors.lastname: Boige
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D009944:Organoplatinum Compounds; D003841:Deoxycytidine
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