A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer.

This study investigated the maximum tolerated dose of S-1 based on the frequency of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients with locally advanced pancreatic cancer. S-1 was administered orally at escalating doses from 50 to 80 mg m(-2) b.i.d. on the day of irradiation during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m(-2) seven patients) were enrolled in this trial. At a dose of 70 mg m(-2) S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 haemorrhagic gastritis, whereas no patients at doses other than 70 mg m(-2) demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed a partial response. The median progression-free survival time and median survival time for the patients overall were 8.9 and 11.0 months, respectively. The recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m(-2) day(-1). A multi-institutional phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway.