Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Lancet Oncol. 2010 Jan;11(1):48-54. doi: 10.1016/S1470-2045(09)70333-X. Epub 2009 Nov 20.

Abstract

Background: Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([(18)F]FDG)-PET correlate with clinical outcome.

Methods: Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m(2) (10 mg/m(2) per min) and oxaliplatin 85 mg/m(2) (2-h infusion). [(18)F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231.

Findings: 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7.0 months (95% CI 5.3-10.3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [(18)F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUV(max)) after two cycles of treatment (5.72 [SD 2.01] at baseline; 3.73 [SD 1.88] after two cycles; p<0.0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, -2.80 [SD 1.95] vs five patients, 1.41 [SD 3.13]; p=0.009). Change in SUV(max) was a significant predictor of PFS (HR 1.35, 1.14-1.60, p=0.0006) and overall survival (1.25, 1.05-1.50, p=0.01).

Interpretation: GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUV(max) on [(18)F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival.

Funding: Genentech Oncology and Sanofi-Aventis.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biliary Tract Neoplasms / diagnostic imaging*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / mortality
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Female
  • Fluorodeoxyglucose F18*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Positron-Emission Tomography*
  • Proportional Hazards Models
  • Radiopharmaceuticals*
  • Risk Assessment
  • Time Factors
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Radiopharmaceuticals
  • Deoxycytidine
  • Fluorodeoxyglucose F18
  • Bevacizumab

Supplementary concepts

  • gemcitabine-oxaliplatin regimen

Associated data

  • ClinicalTrials.gov/NCT00361231