Adjuvant Therapy of Melanoma
Melanoma incidence is rising faster than other solid tumors, with an increase in incidence of a 1000% since 1935. The US death toll attributable to melanoma in 2002 approaches 8,000 people a year. Melanoma arises in the skin and ought to be susceptible to early detection, and is thus uniquely relevant to generalists and dermatologists among cancers. Immense interest in melanoma, its pathophysiology, and its treatment has arisen with recent understanding of immunology, molecular biology, and in particular the clinical evidence of immunogenicity for melanoma, with an array of antigens defined serologically, with the CD8 (killer) T cell, and CD4 (helper) T cell that are separately reviewed in this issue. The clinical antitumor activity of multiple mediators of the immune system have led to adoption of melanoma as a model tumor for evaluation of new immunologic and molecular biological interventions. The only 2 agents that have been accepted on rigorous review for the systematic treatment of this disease in the past 25 years are recombinant biologicals–interferon alfa-2b and interleukin-2. Unfortunately, no trial ever conducted in a large multicenter forum has yet shown prolongation of overall survival in advanced distant metastatic disease. Thus, surgical, medical, and dermatologic oncologists have turned to interventions in the adjuvant arena, directed at patients who have undergone potentially curative operations for melanoma, but remain at intermediate or high risk of disease relapse and mortality. Numerous randomized controlled trials have been performed to investigate a range of adjuvant therapies for melanoma to improve overall and relapse-free survival. With one exception, the results obtained in all past multicenter randomized trials of chemotherapy, biotherapy, tumor vaccines, and hormonal agents tested to date have failed to show significant durable and reproducible benefits.