Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial

Background Less than half of patients with melanoma that has spread to local draining regional lymph nodes (stage III melanoma) live with no disease for 5 years or longer after surgery. We aimed to see whether interferon alpha-2a increased survival prospects in these patients. Methods 444 patients from 23 centres in the WHO Melanoma Programme had complete lymphadenectomy for pathologically proven regional nodal spread of melanoma and were randomly assigned to receive either 3 MU subcutaneously of recombinant interferon alpha-2a three times a week for 3 years, or to observation alone after surgery. Patients were stratified by centre, nodes with macroscopic or microscopic melanoma, number of affected nodes, and nodal metastatic spread. Treatment was continued for 3 years or until first sign of relapse. Findings 424 patients entered the study. 5-year disease-free survival of those who had surgery plus interferon alpha-2a was 27·5% (95% Cl 21·7–33·6); for those who received surgery alone, survival was 28·4% (22·5–34·6) (p=0·50). Neither Kaplan-Meier cumulative survival rates, nor multivariate anaysis of survival, showed a difference between those who had surgery and interferon alpha-2a (35%, 95% Cl 29–42) and those who had surgery alone (37%, 31–44). Interpretation Patients with melanoma that has spread to the local draining regional lymph nodes tolerate well 3 MU of interferon alpha-2a given subcutaneously three times a week for 3 years, but this treatment does not improve either disease-free or overall survival.