The role of interferon in cancer therapy: a current perspective.

Recombinant interferon alpha has now been established as having a distinct if narrow role when used as a single agent in cancer therapy. The responses to single-agent therapy can be grouped as shown in Table 7. Interferon is likely to be the treatment of choice for hairy cell leukemia and possibly also for symptomatic nodular lymphoma. Interferon is very useful in treating papillomas and condylomas, and its role as a local agent will probably expand. The list of responding cancers for alpha interferon or other subtypes as a single agent is unlikely to expand greatly over the next few years. Nevertheless, in both melanoma and renal carcinoma, meaningful responses do occur. It is important to be aware of the possibility of both delayed and increasing extent of response with duration of treatment; adequate trials of interferon may therefore require longer periods of treatment than does conventional chemotherapy. Furthermore, because prior failure to respond to chemotherapy does not predict response to interferon, its use as a second-line agent should also be considered. The future of such biological agents, however, clearly lies in combination with other agents as the "fourth arm" of cancer therapy. The challenge is to define what the role of that fourth arm will be. There seems to be a clear choice with the interferons. They can be used at pharmacological doses, in which case their antiproliferative effect is likely to be due to induction of certain enzymes that result in a cytostatic effect in susceptible cancers, of which there are a limited but therapeutically important number. Alternatively, the interferons can be used at physiological doses, which are more likely to cause immunological and cell membrane effects such as NK-cell stimulation, as well as Fc-receptor and tumor-antigen expression. Thus, combination with cytotoxic agents may well require high doses, whereas combination with other biological agents, such as monoclonal antibodies or LAK cells, may be most effective at much lower doses. Over the next few years it will be important to establish the optimal biological doses of the interferons, so that we can maximize their usefulness in therapy and avoid the trap of thinking of them as purely cytotoxic agents.