Combination chemotherapy of S-1 and taxanes in Korea

Various combination treatments incorporating S-1 are undergoing clinical trials in Korea, especially combinations with taxane, oxaliplatin, or irinotecan. In a phase I study to estimate the maximum tolerated dose of docetaxel in combination with S-1 administered at a fixed dose of 40 mg/m² twice daily on days 1–14 of each 3-week cycle in patients with advanced gastric cancer, 60 mg/m² docetaxel was declared to be the maximum tolerated dose. A phase I/II study of the same schedule of combination chemotherapy with S-1 plus docetaxel reported doses of S-1/docetaxel of 40/75 mg/m² as the maximum tolerated dose. In a phase I study of S-1 plus weekly docetaxel, the patients received variable doses of docetaxel administered intravenously over 1 h on days 1 and 8 and S-1 administered on days 1–14 of each 3-week cycle. The maximum-tolerated doses of S-1 and docetaxel were determined to be 45 mg/m² and 35 mg/m² in this study. A phase I/II study of docetaxel plus S-1 combination chemotherapy from Korea reported a response rate of 43.3%. Also, a phase II study of paclitaxel plus S-1 as first-line therapy in patients with advanced or relapsed gastric cancer showed an overall response rate of 49%. The most frequent significant toxicities in combination chemotherapies with taxane plus S-1 were neutropenia and febrile neutropenia. However, nonhematological toxicities were mild to moderate. A taxane plus S-1 combination regimen could be a new standard regimen for advanced gastric cancer, given its significant activity and favorable toxicity pattern.