1. ¹Department of Surgical Oncology and Digestive Surgery, Kagoshima University, Kagoshima, Japan
2. ²Frontier Science Research Center, Kagoshima University, Kagoshima, Japan

Correspondence: Dr H Shinchi, E-mail: shinchi@m.kufm.kagoshima-u.ac.jp

Received 29 August 2006; Revised 15 March 2007; Accepted 19 March 2007; Published online 17 April 2007.

Abstract

In this phase-I trial, we evaluated the safety of S-1, a novel oral fluoropyrimidine anticancer agent, combined with external-beam radiotherapy (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients. Patients had histologically proven unresectable locally advanced or metastatic pancreatic cancer. S-1 was administered orally twice daily. External-beam radiotherapy was delivered in fractions of 1.25 Gy 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S-1 was given at five dose levels: 60 mg m^–2 day^–1 on days 1–7 and 15–21 (level 1), 1–14 (level 2), and 1–21 (level 3a) and 80 mg m^–2 day^–1 on days 1–21 (level 3b) and 1–28 (level 4). We studied 17 patients: dose levels 1 (four patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4 (three patients). One patient in level 1 (grade 3 vomiting) and two patients in level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5 partial responses (35%), 11 cases of stable disease, and one case of progressive disease. CA19–9 levels of less than half the starting values were observed in 8 of 16 (50%) patients. S-1 at a dose of 80 mg m^–2 day^–1 given on days 1–21 is safe and recommended for phase-II study in patients with locally advanced and unresectable pancreatic cancer when given with EBRT.