Potential applications of the interferons in oncology: lessons drawn from studies of human melanoma

The rationale for application of interferons in the treatment of melanoma is based on evidence suggesting that this tumor exhibits antigens capable of eliciting a host immune response. Agents that act as immunomodulators or that enhance the expression of tumor antigens may have greater therapeutic potential than agents that act solely as direct cytotoxic or antiproliferative agents. Data suggest that interferons may manifest all three categories of antineoplastic function. Early empirical trials with naturally derived leukocyte-lymphoblastoid interferons yielded poor therapeutic results. In contrast, in four subsequent trials conducted using recombinant DNA-synthesized interferon alfa 2's at three independent institutions, an objective response rate of 19% was achieved. Of the 20 responses obtained in the 102 evaluable patients, eight were complete. Three further preliminary reports enlarged the data base to 215 patients, 35 of whom showed an objective response. The response to systemic interferon alfa-2's appears to be associated with several factors including (1) continuous treatment for periods of up to several months at dosages greater than 10 MU/day intravenously (IV) or intramuscularly (IM) or 12.5 MU/m2/day IM on alternate days, and (2) metastatic tumor involving nonvisceral sites and the lung. The analysis of immunologic and other factors that may be related to or predictive of response has been hampered by the low overall frequency of response. New trials currently in progress to determine the efficacy of interferon alfa-2's as an adjuvant to surgery in candidates at high risk of recurrence and the efficacy of interferon alfa-2's when used in combination with gamma interferon, other biological agents, and chemotherapy may allow these questions to be resolved.