A phase I study of S-1 in combination with nab-paclitaxel in patients with unresectable or recurrent gastric cancer

In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study. The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m(2) twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m(2) on day 1 or 8. Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m(2) twice daily plus nab-paclitaxel 220 mg/m(2) on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m(2) twice daily plus nab-paclitaxel 260 mg/m(2) on day 1). The most common grade 3-4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab-paclitaxel or S-1 alone. Based on the present results, the RD was determined as level 3a (S-1 80 mg/m(2) twice daily plus nab-paclitaxel 260 mg/m(2) on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer.