Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

Abstract

162 Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m2/day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m2 and 100mg/m2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m2 and 100mg/m2, respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.