Purpose: A phase I study of TCF therapy, which consists of paclitaxel (TXL: Taxol) + cisplatin (CDDP) + 5-fluorouracil (5-FU), in advanced gastric cancer patients was performed to determine the recommended dose (RD) for a phase II study by checking the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of 5-FU above the fixed dose of TXL and CDDP.
Methods: The doses of TXL and CDDP were fixed at 80 and 25 mg/m(2), respectively, while that of 5-FU was increased by 100 mg/m(2 )in each cohort from 300 mg/m(2) (level 1) to a maximum of 600 mg/m(2) (level 4). One cycle consisted of administration of these agents once per week for 3 weeks, every 4 weeks.
Results: A total of twelve eligible patients were included in this study. At level 1, two of three cases showed grade 3 leukopenia. At level 2, one of three cases showed grade 4 neutropenia (recovered within 3 days), and another one case showed grade 3 neutropenia. At level 3, one of three cases showed grade 3 neutropenia, and at level 4, one of three cases showed grade 4 neutropenia (recovered within 3 days), with grade 3 neutropenia in the other two cases. Even at the highest dose administered, none of the patients showed DLT. Moreover, no non-hematological toxicity judged to be DLT was observed through all levels. Six of the twelve patients had measurable disease, and the overall response rate was 83%.
Conclusions: Although the MTD level was not determined, based on the observed efficacy and the results of other clinical trials, the recommended doses of TXL, CDDP, and 5-FU for the TCF regimen were set as 80, 25, and 600 mg/m(2), respectively, and a phase II study to investigate the clinical effectiveness and safety of this regimen has now begun.