Prospective, randomized, multicenter, double-blind placebo-controlled trial comparing adjuvant interferon alfa and isotretinoin with interferon alfa alone in stage IIA and IIB melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group

J Clin Oncol. 2005 Dec 1;23(34):8655-63. doi: 10.1200/JCO.2004.00.8128. Epub 2005 Oct 31.


Purpose: The combination of interferon alfa (IFNalpha) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFNalpha alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFNalpha and isotretinoin compared with IFNalpha alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB.

Patients and methods: In a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFNalpha and isotretinoin (isotretinoin group; 206 patients) or IFNalpha and placebo (placebo group; 201 patients) after excision of the primary tumor. IFNalpha was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients < or = 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months.

Results: A scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility.

Conclusion: The addition of isotretinoin to an adjuvant treatment of low-dose IFNalpha in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Basal Cell / drug therapy
  • Carcinoma, Basal Cell / secondary
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / secondary
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Double-Blind Method
  • Europe
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Hyperlipidemias / chemically induced
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Isotretinoin / adverse effects
  • Isotretinoin / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Quality of Life
  • Skin Diseases / chemically induced
  • Treatment Outcome


  • Antineoplastic Agents
  • Interferon-alpha
  • Isotretinoin