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.

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.

• Authors: Andrew X Zhu, Jeffrey A Meyerhardt, Lawrence S Blaszkowsky, Avinash R Kambadakone, Alona Muzikansky, Hui Zheng, Jeffrey W Clark, Thomas A Abrams, Jennifer A Chan, Peter C Enzinger, Pankaj Bhargava, Eunice L Kwak, Jill N Allen, Sanjay R Jain, Keith Stuart, Kerry Horgan, Susan Sheehan, Charles S Fuchs, David P Ryan, Dushyant V Sahani
• Journal: The Lancet. Oncology (Lancet Oncol) Vol. 11 Issue 1 Pg. 48-54 (Jan 2010) ISSN: 1474-5488 [Electronic] England
• PMID: 19932054 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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