Randomized, double-blind phase II study to compare nitroglycerin plus oral vinorelbine plus cisplatin with oral vinorelbine plus cisplatin alone in patients with stage IIIB/IV non-small cell lung cancer (NSCLC)

Abstract Objectives Adding nitroglycerin to the combination of vinorelbine plus cisplatin has been reported to improve the overall survival (OS) of Asian patients with stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug delivery based on changed vascular tonus. The main objective of our study was to evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a Caucasian population. Methods 66 chemonaive patients with stage IIIB/IV NSCLC received oral vinorelbine (first cycle 60 mg/m 2 , subsequent cycles: 80 mg/m 2 in the absence of any hematological toxicity ≥grade 3 in cycle 1) once daily on days 1 and 8 of each cycle and cisplatin (80 mg/m 2 i.v.) on day 1 of each cycle (q3w). Nitroglycerin (arm A, n  = 34) or placebo patches (arm B, n  = 32) were administered once daily from day −3 to day 2 of each cycle and were removed about 12 h after administration. One nitroglycerin patch contained 25 mg nitroglycerin. Results Median age was 62.5 (33–82) years. In the overall population ( n  = 66), the objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0–39.6), with a disease control rate (DCR) of 57.6% (95%CI: 44.8–69.7), a median time to progression (TTP) of 4.8 months ( n  = 58; 95%CI: 3.4–5.9) and a median overall survival (OS) of 11.5 months (95%CI: 7.9–13.6). ORR and DCR were numerically higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%, respectively), whereas TTP and OS were comparable. The main hematological and non-hematological toxicities grade ≥3 were moderate with no significant differences between the two treatment arms. Conclusions Overall, oral vinorelbine plus cisplatin showed a high level of efficacy and adequate tolerability in first line treatment of NSCLC. Despite the low sample size per group the results seem to confirm the previous results reported in Asian patients.