Journal of Translational Medicine 2013-01-01

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

Antonio Daponte, Simona Signoriello, Luigi Maiorino, Bruno Massidda, Ester Simeone, Antonio Maria Grimaldi, Corrado Caracò, Giuseppe Palmieri, Antonio Cossu, Gerardo Botti, Antonella Petrillo, Secondo Lastoria, Ernesta Cavalcanti, Pasquale Aprea, Nicola Mozzillo, Ciro Gallo, Giuseppe Comella, Paolo Antonio Ascierto

Index: J. Transl. Med. 11 , 38, (2013)

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Abstract

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.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-α2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-α2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs. C+D) and IFN-α2b (groups A+C vs. B+D).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-α2b 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-α2b (p=0.57). The combination of all three drugs resulted in the highest occurrence of adverse events.No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.ClinicalTrials.gov: NCT01359956.