A phase I study of TS-1 plus carboplatin in patients with advanced non-small-cell lung cancer.

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5-flurouracil, and two modulators. A phase I study of TS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSCLC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSCLC were analyzed. The grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). These toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed DLT at this dose. The RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).