Randomized phase II trial of daily administration versus alternate-day administration of S-1 in patients with advanced non-small cell lung cancer

Objective The standard regimen of S-1 monotherapy, comprising 4 weeks of administration followed by 2 weeks of rest, frequently causes gastrointestinal toxicity. Studies indicate that alternate-day administration of S-1 decreases gastrointestinal toxicity in advanced gastric cancer. We conducted a randomized phase II trial among patients with previously treated non-small cell lung cancer (NSCLC) to compare safety and efficacy between alternate-day administration and the standard regimen. Patients and methods Patients were randomly assigned to the standard regimen (S-arm): S-1, 80–120 mg/day according to body surface area (BSA) daily for 4 weeks, followed by 2 weeks rest, every 6 weeks until progressive disease (PD) or alternate-day administration (A-arm): S-1, 80–120 mg/day according to BSA on Mondays, Wednesdays, Fridays and Sundays every week until PD. The primary endpoint was safety. Secondary endpoints included objective response, progression-free survival, overall survival, and completion rate of the first treatment cycle. Results In total, 61 patients were recruited: 31 to the S-arm, and 30 to the A-arm. In safety analysis, grade 3 or 4 adverse reactions were observed for 10 (32.3%; 95%CI: 15.8–48.7%) and 3 (10.0%; 95%CI:0-20.7%) patients in the S-arms and A-arms, respectively. The main grade 3 or 4 toxicities were anorexia, 19.4%/0%, and diarrhea, 9.7%/0%, respectively. No treatment-related death was observed. The objective response rate was 3.2% and 0.0%; the disease control rate was 45.2% and 56.7%, and the median progression-free survival was 2.7 months and 2.1 months in the S-arm and A-arm, respectively. The completion rate of the first cycle was 77.4% and 80.0%, respectively. Conclusion Alternate-day administration of S-1 demonstrated less toxicity without attenuating therapeutic effectiveness among patients with NSCLC. These are promising data to proceed on to validation studies of alternate-day administration of S-1.