A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer

Abstract

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1-14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38 degrees C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

“…The incidences of grades 3 and 4 toxic effects in our study are consistent with those reported previously for the same S-1 combination regimen (Ajani et al, 2006b;Inokuchi et al, 2006). When paclitaxel was administered every 3 weeks with or without 5-FU, non-haematological toxicity, apart from alopecia of grade 3 or higher, included neuropathy (0 -29%), myalgia (0 -27%), and nausea/vomiting (0 -7%) Yamada et al, 2001;Arai et al, 2003;Hokita et al, 2005;Kondo et al, 2005;Inokuchi et al, 2006). Although there are limitations in comparing the results of different studies because of differences in factors such as the dose and treatment schedule of paclitaxel therapy and the extent of prior treatment, neuromuscular toxicity, the most common adverse effect of paclitaxel, was very mild in our study.…”

“…In 2005, Hokita et al (2005) reported the results of a phase I study of S-1 combined with paclitaxel in patients with advanced gastric cancer. The response rate was 53%, and the MST was 428 days.…”

A multi-center phase II study of S-1 plus paclitaxel as first-line therapy for patients with advanced or recurrent unresectable gastric cancer

“…In Korean trial, the dose was Wnely adjusted compared with Japanese trials in which S-1 dose by body surface area (BSA) was roughly divided into three levels. The actual dose was nearly same in patients with BSA between 1.4-1.7 m 2 of two nations paclitaxel 50-60 mg/m 2 , weekly [6,7,9,13,17,20,23]. The most common dose limiting toxicities were grade 3 diarrhea or grade 4 neutropenia.…”

“…Paclitaxel has synergistic antitumor eVects with 5-Xuorouracil (5-FU) according to clinical trials as well as preclinical studies, and a diVerent spectrum of side eVects [12,18]. Several clinical trials of S-1 and paclitaxel combination therapy have been conducted in Japan [6,7,9,13,17,20,23]. The response rate has been reported to be 40-60% with the schedule of S-1 80 mg/m 2 for 14 days plus weekly paclitaxel 50-60 mg/m 2 on days 1 and 8.…”

Multicenter phase II study of weekly paclitaxel plus S-1 combination chemotherapy in patients with advanced gastric cancer

“…Several clinical trials of S-1 and paclitaxel combination therapy have been conducted in Japan [28][29][30][31][32][33]. The response rate has been reported to be 40%-60% with the schedule of S-1 80 mg/m 2 for 14 days plus paclitaxel 50-60 mg/m 2 on days 1 and 8 or days 1 and 15.…”