A Multicenter, Randomized Phase II Study of V (Vinorelbine)/C (Cisplatin)/B (Bevacizumab) Followed by D (Docetaxel)/G (Gemcitabine)/B Versus D/ C /B as a First-Line Therapy for Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

ABSTRACT Background The combination of D/G has shown equal activity compared to the platinum-based doublets, which is considered the cornerstone for the treatment of NSCLC, with a more favorable toxicity profile. Sequential therapy with four active drugs, including C, was recently investigated and attributed a favorable response rate (Pallis A, et al; Lung Cancer 2006 52(2): 165-71). Incorporation of B to the standard platinum-based regimen improved its clinical outcome. The efficacy of sequential four drug treatment in combination with B was compared to the standard non platinum-based regimen combined with B. Methods Seventy-seven treatment-naive patients with unresectable stage IIIB and IV non-squamous NSCLC were randomized to receive V 60 mg/m2 PO on day 1 and 8, C 80mg/m2 IV on day 1 and B 15 mg/kg IV on day 1, for 3 cycles followed by D 75 mg/m2 IV, G 1100 mg/m2 IV and B 15 mg/kg IV, all on day 1 (Arm A) or D 75 mg/m2 IV, C 80mg/m2 IV and B 15 mg/kg IV on day. The cycles were repeated every 3 weeks for a total of 6 cycles. The primary endpoint was response rate (RR) and the secondary end points overall survival (OS) and progression free survival (PFS). Results Thirty-nine patients were randomized to arm B (control) and 38 patients to the sequential arm. The overall RR was 36.8% and 46.2% in arm A and B, respectively (p= 0.49). There were 3 complete responses, one in arm A. Median PFS was 5.77 and 5.53 months in arm A and B, respectively (p= 0.368). Median OS was 16.9 and 10.9, respectively (p= 0.39). The estimated 1 and 2-year survival for arm A versus B were 64.1% and 35% versus 48.4% and 24%, respectively. No difference in the toxicity profile was observed between the 2 arms, although more cycle-delays were observed in the experimental arm (29.5 versus 12.2; p Conclusion Sequential treatment with four active drugs is feasible and safe. The combination attributes encouraging results compared to the standard platinum-based regimen. Disclosure All authors have declared no conflicts of interest.