The role of interferons in the treatment of solid tumors

Originally described as antiviral agents, interferons (IFN) were investigated as potential anticancer agents because of their antiproliferative and cytotoxic effects, their ability to activate specific components of the immune system, and their relatively modest toxicities. Interest intensified when durable complete remissions were observed in patients with hairy cell leukemia after IFN treatment; modest, but reproducible activity also was found against tumors such as melanoma and renal cell carcinoma which are unresponsive to conventional chemotherapy. Observations of synergy between IFN and cytotoxic drugs in vitro and in vivo suggested that IFN may have additional utility as modulating agents.

Reports of major clinical trials using IFN either alone or in combination with other agents were reviewed. Activity was identified by disease site. Correlations were made with important preclinical studies.

IFN has reproducible, but modest, single-agent activity against melanoma, renal cell carcinoma, and acquired immune deficiency syndrome-related Kaposi sarcoma. IFN may be useful in the treatment of a number of benign, in situ, or low-grade tumors. IFN in combinations with cytotoxic agents have demonstrated activity in solid tumors. Clinical trials using combinations of IFN and 5-fluorouracil or dacarbazine suggested a potential benefit for the combination compared with single-agent chemotherapy. These are preliminary findings that require confirmation, but they suggest that combination therapy should be investigated further. In early preclinical and clinical studies, combinations of IFN and other biologic agents, hormonal agents, and radiation therapy appear to be interesting.

The role of IFN in the treatment of solid tumors may be evolving from that of single-agent therapy to combination therapy with other active agents. Additional studies are required to determine the optimal doses, schedules, and sequencing of these combination therapies.