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

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Abstract

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-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).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-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.Conclusions: No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.Trial registration: ClinicalTrials.gov: NCT01359956.

Original languageEnglish
Article number38
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - Feb 13 2013

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fotemustine
Dacarbazine
Interferons
Melanoma
Survival
Disease-Free Survival
Hazards
Therapeutics

Keywords

  • Dacarbazine
  • Fotemustine
  • Interferon-α
  • Melanoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

@article{a6059bc1d6534abfa3b422d5533fb102,
title = "Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma",
abstract = "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-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).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-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.Conclusions: No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.Trial registration: ClinicalTrials.gov: NCT01359956.",
keywords = "Dacarbazine, Fotemustine, Interferon-α, Melanoma",
author = "Antonio Daponte and Simona Signoriello and Luigi Maiorino and Bruno Massidda and Ester Simeone and Grimaldi, {Antonio Maria} and Corrado Carac{\`o} and Giuseppe Palmieri and Antonio Cossu and Gerardo Botti and Antonella Petrillo and Secondo Lastoria and Ernesta Cavalcanti and Pasquale Aprea and Nicola Mozzillo and Ciro Gallo and Giuseppe Comella and Ascierto, {Paolo Antonio}",
year = "2013",
month = "2",
day = "13",
doi = "10.1186/1479-5876-11-38",
language = "English",
volume = "11",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
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TY - JOUR

T1 - Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma

AU - Daponte, Antonio

AU - Signoriello, Simona

AU - Maiorino, Luigi

AU - Massidda, Bruno

AU - Simeone, Ester

AU - Grimaldi, Antonio Maria

AU - Caracò, Corrado

AU - Palmieri, Giuseppe

AU - Cossu, Antonio

AU - Botti, Gerardo

AU - Petrillo, Antonella

AU - Lastoria, Secondo

AU - Cavalcanti, Ernesta

AU - Aprea, Pasquale

AU - Mozzillo, Nicola

AU - Gallo, Ciro

AU - Comella, Giuseppe

AU - Ascierto, Paolo Antonio

PY - 2013/2/13

Y1 - 2013/2/13

N2 - 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-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).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-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.Conclusions: No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.Trial registration: ClinicalTrials.gov: NCT01359956.

AB - 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-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).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-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.Conclusions: No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.Trial registration: ClinicalTrials.gov: NCT01359956.

KW - Dacarbazine

KW - Fotemustine

KW - Interferon-α

KW - Melanoma

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U2 - 10.1186/1479-5876-11-38

DO - 10.1186/1479-5876-11-38

M3 - Article

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JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

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