Phase I study of paclitaxel and cisplatin for patients with advanced or recurrent gastric cancer.

Background/Aims: The present phase I study was planned to define the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of the combination of paclitaxel and cisplatin in patients with advanced or recurrent gastric cancer, and to recommend a dose for the phase II study. Methodology: Patients were required to have performance status of 0 to 1, to be between 15 and 74 years of age, and to have adequate organ function. The cisplatin was administered at a fixed dose of 25mg/m 2 and paclitaxel was administered at four dose levels (60, 70, 80, and 90mg/m 2 ). Plasma sampling was performed to characterize the pharmacokinetics and pharacodynamics of paclitaxel. Results: All of the 15 patients entered were assessable for toxicity and response and were subject to analysis of dose-limiting toxicity (DLT) and MTD. Neutropenia (grade 4, for 3 days or more; n=2) indicated DLT at dose level 4 (90mg/m 2 ). The MTD for this regimen was 90mg/m 2 /week of paclitaxel for 3 weeks. Tumor response occurred in 7 of the 15 patients and the overall response rate was 57.1%. The pharmacokinetic profiles of paclitaxel were similar to those observed after the administration of each dose as a single agent. Conclusions: Our study demonstrated that the level 3 dosage (80mg/m 2 of paclitaxel and 25mg/m 2 of cisplatin) is recommended for this combination chemotherapy. This phase I study showed favorable antitumor activity and fewer adverse reactions relative to other types of chemotherapy.