Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial)

Purpose We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer. Methods We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/m(2), nab-paclitaxel 90 mg/m(2), S-1 60/80/100 mg/day (< 1.25 m(2)/1.25-1.50 m(2)/ > 1.5 m(2))]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned. Results From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m(2), nab-paclitaxel 90 mg/m(2), and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response. Conclusion We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007).

Automated summary

The study defined the maximum tolerated dose and the recommended dose for the combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Neutropenia was the most frequently observed toxicity, while other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response.