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 - 26/09/12
, Jeffrey A Meyerhardt, MD b, Lawrence S Blaszkowsky, MD a, Avinash R Kambadakone, MD c, Alona Muzikansky, MS f, Hui Zheng, PhD d, Jeffrey W Clark, MD a, Thomas A Abrams, MD b, Jennifer A Chan, MD b, Peter C Enzinger, MD b, Pankaj Bhargava, MD b, Eunice L Kwak, MD a, Jill N Allen, MD a, Sanjay R Jain, MD e, Keith Stuart, MD g, Kerry Horgan, BA h, Susan Sheehan, RN h, Charles S Fuchs, MD b, David P Ryan, MD a, Dushyant V Sahani, MD cSummary |
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 ([18F]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/m2 (10 mg/m2 per min) and oxaliplatin 85 mg/m2 (2-h infusion). [18F]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). [18F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUVmax) 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 SUVmax 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 SUVmax on [18F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival.
Funding |
Genentech Oncology and Sanofi-Aventis.
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Vol 11 - N° 1
P. 48-54 - janvier 2010 Retour au numéro
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