Phase-I trial of UltrapureTM human leukocyte interferon in human malignancy.

A phase-I trial of UltrapureTM human leukocyte (alpha) interferon was performed, in which 15 patients were treated according to a dose-ranging protocol. Five patients were treated at each of these dosage levels: 2 X 10(6) IU/dose, 9 X 10(6) IU/dose, and 15 X 10(6) IU/dose. Doses were given on days 1-5 and 8-12 of a 28-day study period. Serial NK-cell assays were performed in all patients, and failed to show consistent effects referable to treatment. Serum interferon levels were assayed on one patient at the 9 X 10(6) IU and one patient at the 15 X 10(6) IU dose level. In both cases, a significant interferon titer (greater than or equal to 160) was detected in the serum, and this persisted for as long as 12 h. Fever, malaise, and myalgias were associated with therapy. The dose-limiting toxicity was a dose-related leukopenia, with median white blood cell nadirs of 6,500/mm3 (3 X 10(6) IU/dose), 3,200/mm3 (9 X 10(6) IU/dose), and 1,800/mm3 (15 X 10(6) IU/dose) being produced. One patient died in ventricular fibrillation while suffering chest pain after receiving 5 days of treatment at the 15 X 10(6) IU/dose level. Three patients showed minor responses, insufficient to be called partial responses, in association with interferon therapy. We conclude that dose-limiting leukopenia occurs with this schedule of administration of UltrapureTM human leukocyte interferon at 15 X 10(6) IU/dose.