Based upon in vitro and in vivo synergistic activity of Type I and Type II interferons (IFNs) in preclinical in vitro and in vivo studies, we initiated a phase I trial evaluating the doses, safety, and pharmacokinetics of combinations of recombinant DNA-produced human IFN-β(ser) and IFN-γ in 27 patients with cancer. Twenty-four patients were treated with a 2-hour infusion of IFN-γ, followed by a 10-minute iv injection of IFN-β(ser), three times a week. Patients were entered on fixed dose levels of 1 x 106, 3 x 106, 10 x 106, 30 x 106, and 100 x 106 units of each IFN. In addition, three patients were treated at the highest dose level with a 10-minute iv infusion of IFN-γ and a 10-minute iv infusion of IFN-β(ser). The maximally tolerated dose when administered by this schedule for ≥ 4 weeks was 30 x 106 units of each IFN. Dose-limiting side effects at doses of 100 x 106 units of each IFN consisted of fatigue, nausea, vomiting, anorexia, paralytic ileus, and neutropenia. The most common side effects at the three highest dose levels were fever, rigors often requiring parenteral meperidine, and constitutional symptoms. Reversible elevations in SGOT and LDH were also noted. Serum IFN levels were dose related, with peak titers occurring immediately after IFN administration. One patient with a nodular mixed lymphoma had a partial response which has been sustained for over 1 year. We conclude that combinations of IFN-β(ser) and IFN-γ can be safely administered on a chronic basis without enhanced or cumulative toxic effects.
|Original language||English (US)|
|Title of host publication||Cancer Treatment Reports|
|Number of pages||8|
|State||Published - 1987|
ASJC Scopus subject areas
- Cancer Research