Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-alpha in advanced malignant melanoma
Mené sur 260 patients atteints d'un mélanome avancé, cet essai de phase III évalue, du point de vue de la survie globale et de la survie sans progression, l'ajout de fotemustine ou d'interféron-alpha 2b à un traitement de référence à base de dacarbazine
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-alpha2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-alpha2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs. C+D) and IFN-alpha2b (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-alpha2b 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-alpha2b (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-alpha2b to dacarbazine.Trial registration: ClinicalTrials.gov: NCT01359956