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, nab-paclitaxel 90 mg/m, S-1 60/80/100 mg/day (< 1.25 m/1.25-1.50 m/ > 1.5 m)]. 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, nab-paclitaxel 90 mg/m, 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).