title: Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules.
abstract: BACKGROUND
  New therapies are needed to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Various gemcitabine-oxaliplatin combinations have been tested recently in patients with ovarian and pancreatic carcinoma, yielding interesting results with little toxicity. Therefore, the authors evaluated the activity and toxicity of two such combinations in patients with HCC.
  
  
  METHODS
  Twenty-one patients were enrolled prospectively in the study. Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100 mg/m2 on Day 2 (GEMOX-1), and 10 patients received gemcitabine 1500 mg/m2 on Day 1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX-2). Treatment was repeated every 2 weeks until disease progression developed or until unacceptable adverse effects occurred.
  
  
  RESULTS
  All patients were assessable for response and toxicity. Four patients (19%) achieved objective responses (95% confidence interval, 13-26%), including 3 patients in the GEMOX-1 group and 1 patient in the GEMOX-2 group. Ten patients (48%) had stable disease, and 7 patients (33%) experienced disease progression. The median progression-free survival was 5 months, and the median overall survival was 12 months. Fifty-four percent of patients in the GEMOX-1 group and 50% of patients in the GEMOX-2 group had received previous systemic chemotherapy or cisplatin-based chemoembolization. Grade 3-4 hematologic toxicity, according to National Cancer Institute Common Toxicity Criteria, consisted of thrombocytopenia (GEMOX-1 vs. GEMOX-2, 18% vs. 40%) and neutropenia (0% vs. 30%). No Grade 3-4 nonhematologic toxicity was observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients and 7 patients receiving GEMOX-1 and in 7 patients and 1 patient receiving GEMOX-2.
  
  
  CONCLUSIONS
  Gemcitabine-oxaliplatin combination therapy is feasible in patients with advanced HCC. The GEMOX-1 regimen was tolerated better than the GEMOX-2 regimen. Currently, the GEMOX-1 regimen is being evaluated in a Phase II study in previously untreated patients with HCC.
authors.affiliation: Service d'Hépato-gastro-entérologie, Groupe Hospitalier Pitié Salpétrière, Paris, France. jtaieb@club-internet.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Taïeb
authors.forename: Luminita
authors.initials: L
authors.lastname: Bonyhay
authors.forename: Lamia
authors.initials: L
authors.lastname: Golli
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boleslawski
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Tigaud
authors.forename: Thierry
authors.initials: T
authors.lastname: de Baere
authors.forename: Touraj
authors.initials: T
authors.lastname: Mansourbakht
authors.forename: Marie Anna
authors.initials: MA
authors.lastname: Delgado
authors.forename: Laureut
authors.initials: L
authors.lastname: Hannoun
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Valerie
authors.initials: V
authors.lastname: Boige
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine