S-1 is “an oral fluoropyrimidine agent that consists of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate in a molar ratio of 1:0.4:1,” Dr. Isamu Okamoto, Kinki University Faculty of Medicine, Osaka and colleagues note in their report in the current online issue of the Journal of Clinical Oncology.
The investigators previously had favorable results with S-1 in a phase I/II study in combination with carboplatin. If oral S-1 can replace paclitaxel in carboplatin combinations, they point out, it would avoid the need “for premedication to ameliorate paclitaxel-induced hypersensitivity and the 3-hour infusions required for paclitaxel administration.”
For the current study, the researcher randomly assigned 564 previously untreated patients with advanced NSCLC to receive either carboplatin plus paclitaxel (200 mg/m²) on day 1 or carboplatin on day 1 plus oral S-1 (40 mg/m² b.i.d.) on days 1 to 14. “Chemotherapy was repeated every 3 weeks for a maximum of six cycles.”
Outcomes were not statistically different between the two arms. Median overall survival was 15.2 months in the carboplatin and S-1arm, and 13.3 months in the carboplatin and paclitaxel arm. The 1-year survival rates were 57.3% and 55.5%, respectively, according to the report.
However, toxicity differed significantly between the S-1 group and the paclitaxel group. The incidence of leukopenia was 5% vs 33%, respectively, and neutropenia was 21% vs 77%. On the other hand, the rate of thrombocytopenia was higher with S-1 than paclitaxel (33% vs 9%), and more patients in the S-1 arm needed platelet transfusions.
The rate of alopecia seen with S-1 was 9% compared to 77% with paclitaxel, but nausea was more frequent with S-1 than paclitaxel (62% vs 49%).
“Our present study demonstrates the noninferiority of carboplatin and S-1 relative to carboplatin and paclitaxel in terms of overall survival for patients with advanced NSCLC,” Dr. Okamoto and colleagues conclude. “Carboplatin and S-1 is therefore a valid therapeutic option for the first-line treatment of patients with advanced NSCLC.”
Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study
J Clin Oncol 2010;28.