INTERLEUKIN-2 BASED HOME THERAPY OF METASTATIC RENAL-CELL CARCINOMA -RISKS AND BENEFITS IN 215 CONSECUTIVE SINGLE INSTITUTION PATIENTS

Purpose: In 215 consecutive patients with advanced metastatic renal ce ll carcinoma seen at a single institution the efficacy and tolerance o f different subcutaneous recombinant interleukin-2 based home therapie s were assessed. Materials and Methods: Treatment consisted of subcuta neous recombinant interleukin-2 alone and subcutaneous recombinant int erleukin-2 in combination with recombinant interferon-alpha 2 with or without intravenous 5-fluorouracil. Results: Overall objective respons e rate in 215 patients was 33% (95% confidence interval 26 to 39%). Am ong 16 patients receiving recombinant interleukin-2 alone there was 1 partial remission (overall response 6%). In 79 patients receiving reco mbinant interleukin-2 and interferon-alpha 2 in combination 6 complete and 16 partial remissions occurred (overall response 28%). Of 120 pat ients receiving a combination of recombinant interleukin-2, recombinan t interferon-alpha 2 and 5-fluorouracil 13 achieved a complete and 34 a partial remission (overall response 39%). Of all patients 5% achieve d long-lasting remissions and remain disease-free. Multivariate analys es identified pretreatment erythrocyte sedimentation rate greater than 70 mm. per hour and lactic dehydrogenase greater than 280 units per l . as independent prognostic factors of major significance (p less than or equal to 0.0001) in metastatic renal cell carcinoma. Additionally, neutrophil count greater than 6,000/mu l., hemoglobin less than 100 g m./l., extrapulmonary metastases and bone lesions were identified as m inor (p less than or equal to 0.006) prognostic variables. Patients we re assigned to 1 of 3 risk categories according to cumulative risk sco re defined as the function of the sum of all 6 independent variables. In 116 intermediate risk patients 2-year survival was 65% (median surv ival not reached after 32 months) with recombinant interleukin-2, reco mbinant interferon-alpha 2 and 5-fluorouracil, as opposed to 27% 2-yea r survival (median survival 15 months) with recombinant interleukin-2 and interferon-alpha 2 (p < 0.0001), and 0% (median survival 4.8 month s) with single agent recombinant interleukin-2. In the majority of pat ients systemic toxicity of subcutaneous recombinant interleukin-2 base d protocols was limited to grade 1 or 2 constitutional symptoms, that is fever, chills, malaise and anorexia, which allowed for outpatient t herapy. Conclusions: The present outpatient recombinant interleukin-2 triple drug combination protocol was as effective as the most aggressi ve intravenous recombinant interleukin-2 regimen available. Combinatio n home therapy eliminated the need for inpatient and/or intensive care as required for intravenous cytokine administration and, thereby, it substantially improved the therapeutic index and cost-effectiveness of recombinant interleukin-2 therapy in metastatic renal cell carcinoma stratified for risk.