A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma

To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m(2), day 1), nab-paclitaxel (mg/m(2), day 1), and S-1 (mg/day, days 1-7) were 800/100/60-100 at level 1, and 1000/125/60-100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630). We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients. In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m(2), gemcitabine: 1000 mg/m(2) on day 1, S-1: < 1.25 m(2), 60 mg; 1.25-1.5 m(2), 80 mg; > 1.5 m(2), 100 mg twice a day on days 1-7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.