Cancer Chemother Pharmacol. 2010 Feb;65(3):473-80. doi: 10.1007/s00280-009-1052-3. Epub 2009 Jun 24.

Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated  advanced gastric cancer.

Park I, Lee JL, Ryu MH, Chang HM, Kim TW, Sym SJ, Lee SS, Jang G, Yoo C, Bae KS, Kang YK.

Abstract

BACKGROUND: We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate       S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced  gastric  cancer (AGC).

METHODS: Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1on D-5 and D1 of the first cycle.

RESULTS: In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.

CONCLUSIONS: The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.