Pharmacokinetics and biological activity in subcutaneous long-term administration of recombinant interferon-gamma in cancer patients.

ABSTRACT

We have investigated the pharmacokinetics, tolerance, and biological activity of recombinant human interferon-gamma (rHuIFN gamma) administered subcutaneously to cancer patients. Twenty-one patients with lymphoma and metastatic cancer received rHuIFN gamma (in doses of 0.1, 0.25, or 0.5 mg/m2) in two or three injections per week for up to 180 days. The most common adverse effects encountered were flu-like symptoms, fever and fatigue. The increase in body temperature after each administration ranged from 0 to 4 degrees C depending on the individual patient, but was unrelated to the rHuIFN gamma dose or its plasma concentration. The pharmacokinetic response of the patients after the two treatments showed a low intra-individual variability with respect to the plasma concentration/time profiles. However, as observed for the fever side-effect, the interindividual variation (CV greater than 50%) was high for the parameters area under the data points (AUC0-t) and maximum plasma concentration (cmax). Despite this high interindividual variability, the mean values obtained for AUC0-t and cmax after s.c. injection of rHuIFN gamma were approximately proportional to the dose administered the injection of 0.1, 0.25 or 0.5 mg/m2 rHuIFN gamma resulted in AUC0-t values of 15.4, 31.5 or 69.6 ng h/ml, respectively and cmax was found to be 1.0, 2.4 and 4.9 ng/ml, respectively. With this s.c. administration protocol, objective antitumour responses were observed in two patients, but there was no partial or complete remission.