A phase I/II trial of docetaxel (D) and oxaliplatin (O) in patients with advanced gastric cancer (AGC)

Abstract

15615 Background: Several different combination chemotherapies for advanced gastric cancer(AGC) have been studied, but there is no great difference in survival benefit compared to previous studies. We designed this phase I/II study of docetaxel(D)-oxaliplatin(O) combination chemotherapy to determine its dose-limiting toxicity, maximum tolerated dose (MTD) and efficacy as a first line treatment in patients with AGC. Methods: Patients aged 18∼70 years, histologically documented gastric adenocarcinoma with measurable disease and adequate organ functions were enrolled.In phase I study, enrolled patients were divided into three groups by doses, and Level I, II, III received D-O 60mg/m2-100mg/m2, 75mg/m2-100mg/m2, 75mg/m2- 130mg/m2 respectively on day 1 every 3 weeks. In phase II study, subjects treated to maximum of 9 cycles of D and O unless there was documented disease progression, unacceptable adverse event or withdrawal of consent. Results: In phase I, there was no dose limiting toxicity (DLT) at all drug levels, so we determined recommended dose of D-O as 75mg/m2-130mg/m2 on level III. In phase II, additional 47 patients were entered into the study. In total, all 50 patients were evaluable. Median follow up duration was 6.5 months (range 0.7–17.3). Overall response rate was 26% (95% CI, 13.8–38.2%) with only 13 partial responders and median duration of response was 3.9 months (range, 0.2–8.8). The time to progression was 2.3 months (range, 1.4–6.6) and 6 months progression free survival rate was 25% (95% CI, 13.0–37.0%). Median overall survival was not reached, and 1 year survival rate was 77.2% (95% CI, 65.6–88.8%). The main toxicities (more than grade 3 or 4) were febrile neutropenia (14%), diarrhea (10%), neutropenia (8%) and neurotoxicity (8%). Neutropenia occurred in first 4 cycles, especially 1st cycle. On the other hand, neurotoxicity occurred after 6th cycles. Treatment related mortality occurred in one patient due to peritonitis-related sepsis (2%). Conclusions: It should be further investigated to know whether D and O combination chemotherapy might be another feasible option as a first line treatment in patients with AGC. No significant financial relationships to disclose.