Phase II study of oral fluoropyrimidine anticancer agent (S-1) with concurrent external-beam radiotherapy for locally advanced pancreatic cancer

Abstract

15526 Background: S-1 is a new oral fluoropyrimidine anticancer agent and has shown a good efficacy for pancreatic cancer. In the phase I trial, we evaluated the safety of S-1 combined with external-beam radiotherapy (EBRT) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients (ASCO 2006, Br J Ca 2007). This phase I trial determined the recommended of S-1 for the phase II chemoradiotherapy trial to be 80 mg/m2/day given on days 1–21. This phase II study was conducted to evaluate the efficacy and toxicity of EBRT combined with S-1 for locally advanced pancreatic cancer. Methods: Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, ECOG PS 0–1, adequate organ and marrow function, and no prior anticancer therapy. S-1 was given orally at a dose of 80 mg/m2/day twice a day on days 1–21. EBRT was delivered in fractions of 1.25 Gy × 2 per day, totaling 50 Gy per 40 fractions for 4 weeks. After completion of chemoradiotherapy, S-1 was administered for 14 days followed by a 14-day rest period and continued until disease progression or unacceptable toxicity as maintenance. Results: A total of 26 patients have been enrolled to date in this phase II study. Median follow-up period is 10 months (4–27 months). Of the 26 patients, 25 (96%) completed the scheduled course of chemoradiotherapy. The objective tumor responses by RECIST criteria included 9 PR (35%), 13 SD (50%) and 4 PD (15%). Serum CA19–9 decreased > 50% in 11 of 19 evaluable patients (58%). Thus far the median survival time is 14 months and 1-year survival rate is 67%. Although grade 3 rash and anorexia occurred in one patient each, no grade 4 toxicities were observed. Conclusions: Combination therapy of S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer appears to be a promising and well-tolerated approach with consideration of application to outpatients. No significant financial relationships to disclose.