Phase II study of S‐1 plus leucovorin in patients with metastatic colorectal cancer: Regimen of 1 week on, 1 week off

A phase II study of S‐1 plus leucovorin (LV) given in a 4‐week schedule (2 weeks’ administration followed by 2 weeks’ rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2‐week schedule of S‐1 plus LV. Patients with mCRC received oral S‐1 (40–60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S‐1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy‐three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression‐free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment‐related deaths. The pharmacokinetics profiles of S‐1 plus LV in Chinese patients were similar to those in Japanese patients. This 2‐week schedule of S‐1 plus LV showed good efficacy and better tolerability than the 4‐week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular‐targeted drugs. The optimized treatment schedule for S‐1 plus LV was 1 week on and 1 week off.