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.