Phase I trial of natural human interferon β in metastatic malignancy

A phase I trial of natural human β-interferon (nHuIFN-β) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-β was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 × 10⁶ units/m². Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P < 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIKN-β (P < 0.01). Pharmacokinetic data demonstrated a short α half-life of 12.1 ± 2.5 (SE) min and a β half-life of 129.7 ± 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-β. In conclusion, toxicity of nHuIFN-β given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-β resemble those reported with rHuIFN-β_ser.