Alpha interferons: a clinical overview.

The development of the recombinant alpha interferons has provided a prototype for the clinical development of biological compounds. Over 5,000 patients have now been treated with alpha interferons, and from this experience, some general principles relating to the phase I-III testing of biologicals have emerged. Clinical trials of alpha interferon have suggested dose-response relationships and provided a clearer picture of schedule dependence. These trials have also indicated that the extent of tumor burden and identification of sensitive patient subtypes may be critical factors affecting the potential activity of biological compounds. Recent studies using interferon in the treatment of chronic viral hepatitis have also generated promising results, suggesting an even greater antiviral role for the drug. The toxicity profile of the alpha interferons is unusual. Fever and influenza-like symptoms occur in almost all patients at all doses and schedules, and are usually dose limiting. Somnolence and other generally mild CNS effects occur in a small percentage of patients. Hematologic toxicity occurs but is minimal at lower doses and is noncumulative and rapidly reversible at all doses. Gastrointestinal toxicity is mild. No other unusual or unexpected toxicities have been reported, and early reports of cardiovascular toxicity have not been confirmed in large trials. The full role of alpha interferon in antineoplastic and antiviral therapy will be resolved in the coming years. This review summarizes existing safety and efficacy data for the alpha interferons.