title: Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients.
  
  
  METHODS
  Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16.
  
  
  RESULTS
  Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue.
  
  
  CONCLUSIONS
  GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. azhu@partners.org
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Kerry
authors.initials: K
authors.lastname: Horgan
authors.forename: Susan
authors.initials: S
authors.lastname: Sheehan
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Hale
authors.forename: Peter C
authors.initials: PC
authors.lastname: Enzinger
authors.forename: Pankaj
authors.initials: P
authors.lastname: Bhargava
authors.forename: Keith
authors.initials: K
authors.lastname: Stuart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; 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; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine