Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.
BACKGROUND
Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS).


METHODS
We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided.


RESULTS
The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression.


CONCLUSIONS
In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.
Mocellin
Simone
S
Clinica Chirurgica Generale 2, Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy. simone.mocellin@unipd.it
Pasquali
Sandro
S
Rossi
Carlo R
CR
Nitti
Donato
D
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D016017:Odds Ratio; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016898:Interferon-alpha