Phase I trial of recombinant interferon gamma in cancer patients.

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks. After a 2-week rest period, the IV treatment cycle was repeated. Responders were maintained on repeated IV treatment cycles or daily intramuscular (IM) injections. Patients were entered at fixed dose levels of 0.1, 0.5, or 1.0 mg/m2/d. The maximum safely tolerated dose was 0.5 mg/m2. The most common side effects were constitutional symptoms, including fever, chills, fatigue, and myalgias. Reversible and transient increases in hepatic transaminase and decrease in granulocyte counts were seen. Treatment was associated with a dose-dependent increase in serum levels of beta 2 microglobulin. Partial responses (PRs) were observed in one patient with Hodgkin's disease and one patient with chronic lymphocytic leukemia. Fairly constant levels of serum IFN were found at four and six hours during infusion, followed by a rapid decline within one to two hours. We conclude that rIFN-gamma can be safely administered by a six-hour IV infusion and that it can induce in vivo some of the biologic effects reported in in vitro studies.