A biological approach to optimize interferon treatment in hairy cell leukemia.
Progress with the clinical application of interferons to neoplastic diseases has been slow and complicated by the need for attention to a new spectrum of therapeutic and toxic effects manifested by the interferons. In this report, we present a new approach to define clinically effective but atoxic doses of interferon-alpha for treatment of hairy cell leukemia. In order to find in vivo biologically active interferon doses, the biochemical marker neopterin was selected as a means to assess a cellular interferon response in vivo. Subcutaneous administration of minimal doses of recombinant interferon-alpha-2 (5-8 X 10(5) U/day), which induced maximum neopterin release in serum and urine, proved to be clinically effective: Eight of nine patients responded to this dose regimen. This response rate was comparable to that of a conventional dose schedule (3 X 10(6) U/sqm/day) which was also applied to nine patients (eight responders). Whereas no difference in the clinical efficacy between the two therapeutic strategies could be established, toxicity was clearly confined to the conventional dose regimen. These preliminary results suggest that at least in hairy cell leukemia the therapeutic dose range of interferon can be separated from the toxic.
D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage* / Q000009:adverse effects; D007943:Leukemia, Hairy Cell / Q000097:blood / Q000628:therapy* / Q000652:urine; D019798:Neopterin
D007370:Interferon Type I; D001708:Biopterins; D019798:Neopterin