Phase I study of daily S-1 combined with weekly irinotecan in patients with advanced non-small cell lung cancer.

BACKGROUND

S-1 is a novel oral fluorouracil prodrug active against non-small cell lung cancer (NSCLC). To determine the feasibility of S-1 combined with weekly irinotecan for patients with advanced NSCLC, we performed a phase I study to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan.

METHODS

Patients with advanced NSCLC received S-1 (80 mg/m(2)) on days 1-14 and irinotecan (50-80 mg/m(2)) on days 1, 8, and 15 of each 28-day cycle. Three to six patients were treated with each dose of irinotecan, with the MTD defined as the dose at which dose-limiting toxicity (DLT) appeared in 33% of patients.

RESULTS

At doses of 50-70 mg/m(2), no patients experienced any DLT, whereas, at a dose of 80 mg/m(2), two of four patients experienced DLTs. Two patients experienced grade 3 toxicities - neutropenia and diarrhea.

CONCLUSION

The MTD of weekly irinotecan was 80 mg/m(2), making its RD for phase II trials 70 mg/m(2).