Phase II study of cetuximab plus weekly cisplatin and 24-hour infusion of high-dose 5-fluorouracil and leucovorin for the first-line treatment of advanced gastric cancer

Abstract

4567 Background: Cisplatin-HDFL regimen, using weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil (5-FU) and leucovorin, is commonly used in Taiwan for patients with advanced gastric cancer (GC), showing an overall response rate of approximately 60% (95% CI: 45%-76%) [J Clin Oncol (Suppl) 2006; 24(18S): A14063 ]. We have demonstrated that cetuximab is cytotoxic to human GC cells, and has a chemosensitizing effect for cisplatin and 5-FU in GC cells [Proc AACR 2006; 47: A1233]. Methods: All patients had pathologically confirmed metastatic/ recurrent chemonaive GC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, WHO PS 0/1/2, adequate hepatic, renal, and bone marrow functions. Cetuximab 400 mg/m2 was given as 2h infusion, initially (i.e., D1 of cycle 1); and followed by weekly 1h infusion of 250 mg/m2 (i.e., D8, D15, D22 of cycle 1, and D1, D8, D15, D22 of cycle 2). Cisplatin 35 mg/m2 was given as a 24h infusion, admixing with 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 (HDFL), D1, D8. A 24h infusion of HDFL was given on D15. Cycles were repeated every 28 days, and response evaluation was performed every 2 cycles & at the end of protocol treatment. The primary end-point was confirmed objective response rate (RR) by RECIST. Results: Between Dec. 2005 and Nov. 2008, 35 patients (M:19, F:16) with a median age of 56 (40–74) were enrolled and evaluable for response assessment. The overall RR was 68.6% (51–83%, 95% C.I.) with 1 CR and 23 PRs. Among a total of 269 cycles (median: 7, range: 2 to 22+ cycles) given, Gr3/4 neutropenia, infection, and hepatic toxicity developed in 6.0%, 4.8%, and 0.74% of 269 cycles, respectively. Two patients have developed acute hepatitis B flare-up among seven HBsAg (+) carriers, and were well controlled by lamivudine. Gr1, Gr2, and Gr3 acne- like rashes have developed in 57.1%, 31.4%, 5.7%; and Gr1, Gr2, Gr3 paronychia have developed in 40.0%, 8.6%, and 2.9% of 35 patients, respectively. Median PFS (range: 3 to 22+ months) and median OS (range: 3 to 35+ months) was11.0 and 14.5 months, respectively. Conclusions: Cetuximab plus infusional cisplatin-HDFL is a highly effective regimen with low toxicity and favourable survival in the first-line treatment of advanced GC. No significant financial relationships to disclose.