Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials

Cancer Treat Rev. 2003 Aug;29(4):241-52. doi: 10.1016/s0305-7372(03)00074-4.


Background: Several randomised trials have compared interferon-alpha with control as adjuvant therapy for high-risk malignant melanoma. The results of the individual trials have been either inconclusive or even apparently conflicting. To assess all the available evidence we performed a meta-analysis of these trials.

Methods: Standard methods for quantitative meta-analysis based on published data were used. Endpoints evaluated were recurrence-free survival and overall survival. A subgroup analysis by dose of interferon-alpha was performed.

Findings: Twelve trials, comprising 14 comparisons of interferon-alpha with control, with results available were identified. Recurrence-free survival was improved with interferon-alpha: hazard ratio 0.83, 95% confidence interval 0.77 to 0.90, p=0.000003. The benefit on overall survival was less clear (0.93, 0.85 to 1.02, p=0.1) and the confidence interval is compatible both with no benefit and with a moderate, but clinically worthwhile, benefit. There was some evidence of a dose response relationship with a significant trend for the benefit of interferon-alpha to increase with increasing dose for recurrence-free survival (test for trend: p=0.02) but not for overall survival (trend: p=0.8).

Interpretation: This meta-analysis provides the most reliable synthesis of the data currently available. Adjuvant interferon-alpha produces clear reductions in recurrence of high-risk melanoma, with some evidence of an effect of dose of interferon-alpha, but it is unclear whether this translates into a worthwhile survival benefit or not. Additional and more mature data are needed to resolve these issues and an individual patient data meta-analysis should be performed.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Melanoma / drug therapy*
  • Melanoma / surgery
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / surgery
  • Survival Analysis


  • Antineoplastic Agents
  • Interferon-alpha