Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer

Background Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents. Methods Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m 2 dose of CDDP. Results In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18mg/m 2 , with CDDP 3mg/m 2 , to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16mg/m 2 with CDDP, 3mg/m 2 . In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%). Conclusion The RD was determined to be TXL 14mg/m 2 , with CDDP 3mg/m 2 .