SUBCUTANEOUS IL-2 AND LOW-DOSE IFN-ALPHA-2A IN THE TREATMENT OF UNSELECTED PATIENTS WITH ADVANCED RENAL-CELL CANCER

Background: In advanced renal cell cancer (RCC) interleukin-2 (IL-2) a nd interferon-alpha (IFN-alpha) have shown modest clinical activity as single agents, substantial toxicity being associated with IL-2. For d evelopment of a therapeutically active but less toxic regimen a phase II trial of subcutaneous recombinant IL-2 (rIL-2) and low-dose recombi nant IFN-alpha 2a (rIFN-alpha 2a) was initiated in unselected patients with advanced RCC. Patients and Methods: From 26 patients stratified to 2 prognostic subsets differing in ECOG status and risk factors, 16 patients were eligible. One treatment cycle consisted of 18x10(6) IU r IL-2 and 3x10(6) IU rIFN-alpha 2a on days 1-3 of weeks 1-3 with the 4t h week off therapy. Toxicity led to dose reductions of rIL-2 (day 1: 1 8x10(6) IU, day 2: 12x10(6) IU, day 3: 6x10(6) IU). Circulating cytoki nes were determined by sandwich enzyme immunoassays during the first 3 days of treatment. Results: 63 treatment cycles were given to 16 pati ents. The toxicity of the reduced regimen allowed an outpatient therap y (44 treatment cycles). No tumor remission occurred. Stable disease a fter 2 treatment cycles was observed in 44% of all patients and in 70% of low-risk patients. Median survival was 496 days for low-risk patie nts and 57 days for high-risk patients. Immunological monitoring revea led a treatment-related enhancement of interleukin-6 serum levels (day s 1-3) and of tumor necrosis factor-alpha and interferon-gamma serum l evels (day 1). Conclusion: No effect on tumor remission was observed b y this treatment regimen of subcutaneous rIL-2 combined with low-dose rIFN-alpha 2a in unselected patients with advanced RCC. Toxicity neces sitated a dose reduction of rIL-2 for outpatient therapy.