PROSPECTIVELY RANDOMIZED TOXICITY STUDY OF HIGH-DOSE VERSUS LOW-DOSE TREATMENT STRATEGIES FOR LYMPHOBLASTOID INTERFERON

  • 1 January 1985
    • journal article
    • research article
    • Vol. 69  (7-8) , 743-750
Abstract
It is unclear from preliminary laboratory studies whether a high-dose or a low-dose interferon treatment strategy is optimal. As part of an ongoing study of mechanisms of interferon action, the toxicity is a 2-arm protocol was evaluated in which patients were randomly assigned to receive lymphoblastoid interferon by either a low-dose treatment strategy (2 .times. 106 U/m2 daily .times. 28 days, then daily .times. 5 days every other week by i.m. injection) or a high-dose treatment strategy (5 .times. 106 U/m2 by continuous i.v. infusion over 24 h, escalating by 5 .times. 106 U/m2/day as tolerated over 10 days, repeated every 28 days). The main toxic effects in both arms were fever, fatigue and anorexia. Marked interpatient differences within each dose arm greater than differences between arms. Additional significant toxic effects included nausea and vomiting, hypotension, leukopenia, thrombocytopenia and evidence of hepatic toxicity. Minor changes in serum electrolytes were noted. Coagulation studies were normal. The dose-limiting toxic effect for the high-dose arm was myelosuppression. Median maximum tolerated dose among high-dose strategy patients was 18 .times. 106 U/m2, but there was marked interpatient variation. Both dose schedules apparently were relatively well-tolerated. Because of individual variation in tolerance, high-dose treatment should include a dose escalation strategy.