Eligible patients were randomized to receive: (a) VNR 25 mg/m2 on day 1, 8 and 15 plus CDDP 100 mg/m2 on day 1 every 4 weeks or (b) VNR 30 mg/m2 on day 1 and 8 plus CDDP 80 mg/m2 on day 1 every 3 weeks. All patients were chemotherapy-naïve and had an ECOG performance status (PS) of 0–1.
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.
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.