Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-? in advanced malignant melanoma

Background: The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized 2x2 factorial design trial.Methods: A total of 260 patients were randomly assigned to one of four treatment groups: (A) fotemustine and dacarbazine repeated on 3-week cycle; (B) same treatment as (A) plus IFN-?2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-?2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs. C+D) and IFN-?2b (groups A+C vs. B+D).Results: Addition of fotemustine did not significantly improve overall survival (OS) (p=0.28) or progression-free survival (PFS) (p=0.55); Hazard ratio (HR) for OS was 0.93 (95% CI 0.71-1.21). Similarly, addition of IFN-?2b did not improve OS (p=0.68) or PFS (p=0.65); HR for OS was 0.92 (95% CI 0.70-1.20). Overall response rate was not improved by the addition of either fotemustine (p=0.87) or IFN-?2b (p=0.57). The combination of all three drugs resulted in the highest occurrence of adverse events.Conclusions: No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-?2b to dacarbazine.Trial registration: ClinicalTrials.gov: NCT01359956. © 2013 Daponte et al; licensee BioMed Central Ltd.