title: Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients.
abstract: OBJECTIVE
  In 215 consecutive patients with advanced metastatic renal cell carcinoma seen at a single institution the efficacy and tolerance of different subcutaneous recombinant interleukin-2 based home therapies were assessed.
  
  
  METHODS
  Treatment consisted of subcutaneous recombinant interleukin-2 alone and subcutaneous recombinant interleukin-2 in combination with recombinant interferon-alpha 2 with or without intravenous 5-fluorouracil.
  
  
  RESULTS
  Overall objective response rate in 215 patients was 33% (95% confidence interval 26 to 39%). Among 16 patients receiving recombinant interleukin-2 alone there was 1 partial remission (overall response 6%). In 79 patients receiving recombinant interleukin-2 and interferon-alpha 2 in combination 6 complete and 16 partial remissions occurred (overall response 28%). Of 120 patients receiving a combination of recombinant interleukin-2, recombinant interferon-alpha 2 and 5-fluorouracil 13 achieved a complete and 34 a partial remission (overall response 39%). Of all patients 5% achieved long-lasting remissions and remain disease-free. Multivariate analyses 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 < or = 0.0001) in metastatic renal cell carcinoma. Additionally, neutrophil count greater than 6,000/microliters., hemoglobin less than 100 gm./l., extrapulmonary metastases and bone lesions were identified as minor (p < or = 0.006) prognostic variables. Patients were assigned to 1 of 3 risk categories according to cumulative risk score defined as the function of the sum of all 6 independent variables. In 116 intermediate risk patients 2-year survival was 65% (median survival not reached after 32 months) with recombinant interleukin-2, recombinant interferon-alpha 2 and 5-fluorouracil, as opposed to 27% 2-year survival (median survival 15 months) with recombinant interleukin-2 and interferon-alpha 2 (p < 0.0001), and 0% (median survival 4.8 months) with single agent recombinant interleukin-2. In the majority of patients systemic toxicity of subcutaneous recombinant interleukin-2 based protocols was limited to grade 1 or 2 constitutional symptoms, that is fever, chills, malaise and anorexia, which allowed for outpatient therapy.
  
  
  CONCLUSIONS
  The present outpatient recombinant interleukin-2 triple drug combination protocol was as effective as the most aggressive intravenous recombinant interleukin-2 regimen available. Combination 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.
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D018575:Home Care Services, Hospital-Based; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000008:administration & dosage; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D005472:Fluorouracil