A Phase I Study of S-1 and Gemcitabine with Concurrent Radiotherapy in Patients with Non-Metastatic Advanced...

To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer.

Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days).

Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%).

The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.