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


RESULTS
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).


CONCLUSIONS
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.
Wheatley
Keith
K
University of Birmingham Clinical Trials Unit, Park Grange, 1 Somerset Road, Edgbaston, Birmingham, B15 2RR, UK. k.wheathley@bham.ac.uk
Ives
Natalie
N
Hancock
Barry
B
Gore
Martin
M
Eggermont
Alexander
A
Suciu
Stefan
S
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000601:surgery; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016019:Survival Analysis
D000970:Antineoplastic Agents; D016898:Interferon-alpha