Phase I/II study of recombinant interferon α and γ in advanced progressive renal-cell carcinoma

Abstract

In vitro studies have documented the synergistic antiviral and antiproliferative activity of recombinant interferon α (rIFNα) and rIFNγ. Furthermore, rIFNγ is a strong immunomodulator with optimal effects at a relative low dose (0.1 mg/m²). On the basis of these observations, we began a phase I/II study with the combination of rIFNγ at 100 µg/m² (2 × 10⁶ IU/m²) and rIFNα2c 6 µg/m² (2 × 10⁶ IU/m²), injected twice a week subcutaneously. In cases of stable or progressive disease we increased the dose of rIFNα2c every 2 weeks by 6 µg/m² until the maximum tolerated dose was reached. A total of 32 patients with proven progressive renal-cell carcinoma were included. Of the 31 eligible patients, 21 were male and 10 female, their average age was 57.2 years (range 35–72), 28 had had nephrectomy, their median Karnofsky performance status was 90% (70%–100%), and their tumors were localized predominantly to visceral tissue. In 2, response was complete and in 6 it was partial, for a response rate of 25%. The disease had stabilized in 5 patients and progressed in 16. The median duration of partial response was 14 months (8–16 months); of 2 cases of complete response, 1 persists (23+ months), and the other suffered a relapse after 22 months. The median time to response was 24 weeks (18–24 weeks). The maximum tolerated dose of rIFNα was 30 µg/m² (range of 6–36 µg/m²). Side-effects included those known to be associated with interferon treatment. One patient developed septicemia during a period with grade 4 leukopenia. Our study permits no conclusion regarding the additional value of rIFNγ.