Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: A prospective randomized phase III trial of the G.O.I.M. (Gruppo Oncologico Italia Meridionale)

Summary Purpose A phase III randomized trial was carried out to compare two schedules of the vinorelbine (VNR)–cisplatin (CDDP) regimen in patients with locally advanced unresectable poor prognosis stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoints were overall survival (OS) and analysis of toxicity, while secondary endpoints included response rates, time-to-progression (TTP) and quality of life (QoL). Patients and methods Eligible patients were randomized to receive: (a) VNR 25 mg/m 2 on day 1, 8 and 15 plus CDDP 100 mg/m 2 on day 1 every 4 weeks or (b) VNR 30 mg/m 2 on day 1 and 8 plus CDDP 80 mg/m 2 on day 1 every 3 weeks. All patients were chemotherapy-naive and had an ECOG performance status (PS) of 0–1. Results Overall 278 patients were enrolled into the trial. Overall response rate was 34% (95% CL 26–42%) in the weekly VNR/CDDP arm, and 32% (95% CL 24–40%) in patients treated with day 1–8 VNR/CDDP without any statistically significant difference. Median TTP was 4.5 and 4.6 months respectively for weekly VNR/CDDP arm and the day 1–8 VNR/CDDP one. This difference was not statistically significant (log-rank test, p  = 0.818). Median OS was 9.45 and 10 months respectively for weekly VNR/CDDP arm and the day 1–8 VNR/CDDP one without statistically a significant difference (log-rank test, p  = 0.259). The 1- and 2-year survival rates were 31 and 36%, and 10 and 11% respectively. The incidence of severe neutropenia (34% versus 68%; p  = 0.0001) and of febrile neutropenia (5% versus 12%; p  = 0.026), as well as the rate of therapy omissions (10% versus 24%; p  = 0.0037) were higher in the weekly VNR/CDDP arm than in the day 1–8 VNR/CDDP one. The weekly VNR/CDDP regimen was associated with a lower received dose intensity in a statistically significant fashion (9% versus 22%; p  = 0.0001) and with a lower non-statistically significant quality of life score as compared to the day 1–8 VNR/CDDP schedule. Conclusions The combination of day 1–8 VNR plus CDDP every 3 weeks is less toxic and better tolerated than the regimen of weekly VNR plus CDDP every 4 weeks. The two schedules are equivalent in terms of overall response rate, median time-to-progression and overall survival. The combination of VNR on day 1–8 plus CDDP every 3 weeks may be considered as a reference regimen for the treatment of patients with advanced disease and those who deserve a postoperative therapy, and for future studies.