A phase II study of S-1 in patients with metastatic pancreatic cancer

Abstract

4104 Background: The purpose of this study was to determine the efficacy and toxicity of S-1 in patients with metastatic pancreatic cancer. S-1, an oral anticancer agent, contains tegafur (FT: a prodrug of 5-fluorouracil), 5-chloro-2,4-dihydroxypyridine (CDHP: a dehydropyrimidine dehydrogenase inhibitor), and potassium oxonate (Oxo: an orotate phosphoribosyl transferase inhibitor) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1. Methods: Patients with histologically or cytologically confirmed, bidimensionally measurable metastatic pancreatic adenocarcinoma not amenable to surgery or radiotherapy were eligible for the study. Other eligibility criteria included a Karnofsky performance status of 80 to 100%; an age of 20 to 74 years; adequate hematological, renal and liver functions; no prior chemotherapy; and written informed consent. S-1 was administered orally (40 mg/m2) b.i.d. for 28 consecutive days, repeated every 6 weeks. Patients continued to receive additional courses of S-1 until disease progression or the appearance of unacceptable toxicity. Results: Forty-one patients from seven institutions were enrolled between January 2003 and April 2004. One patient deteriorated before receiving treatment and was excluded from further analysis. Out of the 40 eligible patients, 15 patients had partial responses, for an objective response rate of 37.5% (95% c.i.: 22.7 - 54.2%); 11 patients had no change, 13 had progressive diseases, and the final patient was not evaluated. The median survival time was 8.8 months (95% c.i.: 7.5 - 10.8 months). A clinical benefit response was achieved in four of the ten evaluable patients. The main grade 3 - 4 toxicities were neutropenia (12.5%), anorexia (12.5%), diarrhea (7.5%) and nausea (7.5%). Other grade 3 - 4 toxicities, like vomiting, disseminated intravascular coagulation, colitis, hypotension, jaundice and liver dysfunctions, were less frequent. Conclusions: S-1 is active and well tolerated as a single agent chemotherapy in patients with metastatic pancreatic cancer. A prospective randomized trials evaluating S-1 monotherapy is warranted. No significant financial relationships to disclose.