PHASE-I/II STUDY OF RECOMBINANT INTERFERON-ALPHA AND INTERFERON-GAMMA IN ADVANCED PROGRESSIVE RENAL-CELL CARCINOMA

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. © 1990 Springer-Verlag.