Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine

A polyvalent melanoma vaccine prepared from shed antigens stimulates humora l and cellular immune responses and improves survival compared with histori cal controls. We conducted a double-blind, prospectively randomized, placeb o-controlled trial to assess whether this vaccine could slow the progressio n of resected melanoma, Thirty-eight patients with resected melanoma metast atic to regional nodes (American Joint Committee on Cancer stage In) who ha d a particularly poor prognosis on the basis of the nodes being clinically positive or two or more histologically positive nodes were randomly assigne d in a 2:1 ratio to treatment with 40 mug of melanoma or placebo (human alb umin) vaccine, both of which were bound to alum as an adjuvant, Immunizatio ns were given intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months x 2, and then every 6 months for 5 years or until dise ase progression. Twenty-four patients were treated with the melanoma, and 1 4 patients were treated with the placebo vaccine. The groups were evenly ba lanced with respect to prognostic factors. Median length of observation was 2.5 years. There was no local or systemic toxicity. By Kaplan-Meier analys is, median time to disease progression was two and a half times longer in p atients treated with melanoma vaccine compared with that in patients treate d with placebo vaccine, i.e., 1.6 years (95% confidence interval, 1.0-3.0 y ears) compared with 0.6 year [95% confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference was significant at P = 0.03. Overall survival was no longer in the melanoma vaccine-treated group (median overall survival of 3.8 years versus 2.7 years), but this differenc e was not statistically significant. In a double-blind and placebo-controll ed trial, these results suggest that immunization with a melanoma vaccine m ay be able to slow the progression of melanoma, Although statistically sign ificant, these results must be interpreted with caution because they are ba sed on a small number of patients.