A phase I trial of S-1 plus vinorelbine in patients with unresectable advanced or metastatic non-small cell lung cancer
e19098 Background: We reported the efficacy of the combination treatment of tegafur-uracil (UFT) and vinorelbine (VNR) for the elderly patients (pts) (>70) with advanced non-small cell lung cancer (NSCLC) in ASCO 2007 (Abstract - No. 18075). Although the cisplatin-based doublets are still milestone for the pts with advanced NSCLC, non-platinum based doublet regimens remain as a matter of development judging from recent meta-analysis. Tegafur-5-chloro-2,4-dihydroxypyridine-potassium oxonate (S-1), a new oral fluoropyrimidine, has been studied extensively, and appears promising for various kinds of cancers including NSCLC. Thus, we conducted this phase I trial using VNR and new oral fluoropyrimidine, S-1. Methods: Pts with advanced NSCLC, who had received at least one prior platinum-containing regimen, were eligible. In this phase I study, VNR was infused on days 1 and 8, and S-1 was administered from day 2 to day 6 and from day 9 to day 13 of a 3-week cycle. The starting dose of S-1 was 80 mg/m2/day and, if necessary, the dose was decreased to 65 mg/m2/day; VNR was increased from 20 to 25 mg/m2 in this trial. Results: From August 14, 2007 to April 1, 2008, 8 pts enrolled in this study. Median age was 61 (range 49–75). Dose limiting toxicity (DLT) was evaluated during the first 6 weeks of the treatment. No DLT was observed at dose level I (80 mg/m2/day S-1, 20 mg/m2 VNR). At dose level II (80 mg/m2/day S-1, 25 mg/m2 VNR), DLT in the form of neutropenia, hyperglycemia and hyponatremia was observed in 3 of 5 pts. The maximum tolerated dose (MTD) for the present treatment was 80 mg/m2/day S-1 and 25 mg/m2 VNR; the recommended tolerable dose for future phase II trials is therefore 80 mg/m2/day S-1 and 20 mg/m2 VNR. Conclusions: Three-week cycle of VNR (20 mg/m2), infused on days 1 and 8; S-1 (80 mg/m2/day), administered from day 2 to day 6 and from day 9 to day 13, is being examined in our phase II trial for first-or second-line treatment of NSCLC. No significant financial relationships to disclose.