Pharmacokinetics, Single-Dose Tolerance, and Biological Activity of Recombinant Gamma-Interferon in Cancer Patients

We report a clinical study of the pharmacokinetics, toxicity, and biological activity of intravenously and intramuscularly administered recombinant γ-interferon (rIFN-γ) consisting of 143 amino acids. Ten patients with metastatic cancer were given rIFN-γ at doses of 0.01–2.5 mg/m2 by alternating intramuscular and intravenous bolus injections with a minimum intervening period of 72 h. After intravenous administration, rIFN-γ was cleared monoexponentially with a short half-life of 25–35 min as determined by bioassay and enzyme immunoassay. After intramuscular injection, a longer half-life of 227–462 min was measured by enzyme immunoassay. Serum titers were detected by bioassay only at high doses, suggesting partial loss of antiviral activity at the intramuscular site. However, other biological effects were retained as evidenced by fever, chills, and fatigue after both routes of administration and granulocytopenia after intramuscular but not intravenous doses. Two of 10 patients showed objective evidence of tumor regression. These data suggest that further studies with intramuscular as well as prolonged intravenous infusions of rIFN-γ are indicated.