title: Adjuvant subcutaneous interleukin-2 in patients with resected renal cell carcinoma: a pilot study.
abstract: BACKGROUND
  A pilot study was conducted to investigate the toxicity and tolerance to low-dose subcutaneous interleukin-2 (IL-2) for patients with resected renal cell carcinoma (RCC) at high risk for recurrent disease (TNM stages III and IV resected distant metastases).
  
  
  METHODS
  Patients with surgically resected locally advanced (T3-4 or N1-2) or metastatic RCC were randomly assigned to 1 of 4 treatment groups that received different dose levels and schedules of subcutaneous IL-2 as follows: dose level 1, 4 MIU/m2 per day, every other week for 24 weeks (n = 10); dose level 2, 8 MIU/m2 per day, every other week for 24 weeks (n = 9); dose level 3, 4 MIU/m2 per day, weeks 1-4, 9-12, and 17-20 (n = 11); and dose level 4, 8 MIU/m2 per day, weeks 1-4, 9-12, and 17-20 (n = 10). Interleukin-2 was administered in 2 daily doses on days 1-5 of each week indicated. A dose level was considered tolerable if no more than 2 patients experienced grade 3/4 toxicity.
  
  
  RESULTS
  Forty-one patients were entered in the study and 40 were evaluable for toxicity. Therapy was well tolerated at all dose levels and schedules, with most patients (98%) experiencing mild-to-moderate constitutional symptoms. Grade 3/4 toxicity was seen in 8 patients (20%). Interleukin-2 dose reductions were required in 7 patients, and no patient discontinued therapy secondary to toxicity. Of 39 patients evaluable for efficacy, 31 have experienced relapse (79%), and 15 have died (38%). Median survival was 1.4 years, and the 3-year disease-free survival rate was 33%. Median overall survival has not been reached; however, the 3-year survival rate was 70%. There was no statistically significant difference between any of the treatment arms with respect to disease-free survival or 3-year survival (P > 0.54 and P >or= 0.09 for all pairwise comparisons), schedules (dose level 1/2 vs. 3/4; P = 0.46 and P = 0.5), or dose of IL-2 administered (dose level 1/3 vs. 2/4; P = 0.99 and P = 0.1).
  
  
  CONCLUSIONS
  Subcutaneous IL-2 was well tolerated for 6 months in patients with surgically resected RCC at high risk of recurrence. Future adjuvant trials in this setting are not likely to include IL-2 in view of the clinical efficacy and favorable toxicity profiles of selected multitargeted kinase inhibitors.
authors.affiliation: Oncology and Transplantation, University of Minnesota, Minneapolis, USA.
authors.forename: Navneet S
authors.initials: NS
authors.lastname: Majhail
authors.forename: Laura
authors.initials: L
authors.lastname: Wood
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: James
authors.initials: J
authors.lastname: Finke
authors.forename: Thomas
authors.initials: T
authors.lastname: Olencki
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2