A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer.

Background/purpose: S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80 mg/m(2)/day given on days 1-21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).

Methods: Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4 weeks of chemoradiotherapy. S-1 was given orally at a dose of 80 mg/m(2)/day twice daily on days 1-21. Radiotherapy was delivered in fractions of 1.25 Gy twice daily, 5 days per week for 4 weeks (total dose: 50 Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14 days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.

Results: Fifty patients were enrolled in this phase II study. Median follow-up was 14.6 months (range 5.4-58.9 months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18-45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7 months (95% CI, 4.7-11.2 months) and 14.3 months (95% CI, 10.8-20.8 months), respectively. Survival rates at 1 and 2 years were 62 and 27%, respectively.

Conclusions: Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.