학술논문
A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: Interim analysis of the BINGO trial.
Document Type
Academic Journal
Author
Source
Subject
Language
English
ISSN
0732-183X
Abstract
4520 Background: There is no standard regimen for palliative chemotherapy of advanced biliary cancers. The GEMOX regimen is an option (BJC 2008). EGFR over-expression has been observed in advanced biliary cancers suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate.Methods: Patients with advanced biliary cancer, WHO performance status 0-1, and without prior palliative chemotherapy were eligible for this international, open-label, two-stage, randomized phase II trial. Patients received GEMOX (gemcitabine, 1000 mg/m2 [10 mg/m2/min] at day [D]1; oxaliplatin, 100 mg/m2 at D2) alone (arm A) or with cetuximab (500 mg/m2 at D1 or 2, arm B), every 2 weeks. Randomization was stratified according to tumor stage and location, center, and prior treatments. The primary endpoint was 4-month crude progression-free survival (PFS) rate (H0 hypothesis, < 40%; H1, ≥ 60%; planned sample size, 50 patients per arm). Secondary endpoints were response rate, PFS, overall survival, toxicity, early response assessment by PET, and blood/tumor EGFR signalling pathway member analyses. A data safety monitoring board-approved interim analysis was performed at the end of the first stage (18 patients per arm, minimal follow- up 4 months).Results: From October 2007 to October 2008, we enrolled 101 patients (median age, 62 yrs; male, 60%; metastatic, 86%; non-gallbladder, 76%). Among the 36 patients at the time of the interim analysis, the median number of treatment cycles was 6 and 8 in arms A and B, respectively. 76% (arm A) and 67% (arm B) had NCI-CTC grade 3-4 toxicity, mainly cytopenia (41%/39%), peripheral neuropathy (modified Levi's scale grade 2-3: 29%/33%), fatigue (6%/22%), gastrointestinal toxicity (12%/17%), and rash/hypersensitivity (0%/17%). The 4-month PFS rate was 44% (95% CI, 20-70) and 61% (95% CI, 36-83) in arms A and B, respectively.Conclusions: The GEMOX-cetuximab regimen seems well tolerated in patients with advanced biliary cancer. Adding cetuximab to GEMOX showed promising activity and therefore the trial was continued. Updated results on the whole population for primary and secondary endpoints will be available at the meeting. [Table: see text].