title: A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population.
abstract: BACKGROUND
  A prospective multi-institutional phase II trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma.
  
  
  METHODS
  Between February 1997 and March 1999, 47 patients with metastatic renal cell carcinoma, from five institutions, were treated with outpatient s.c. IFN (10 mU/m2/day) on days 1-5, followed by inpatient IL-2 via continuous i.v. decrescendo infusion [18 million International Units (MIU) (I mg)/m2/6 h, followed by 18 MIU/m2/12 h, then 18 MIU/m2/24 h and 4.5 MIU/m2/24 h for the following 3 days] on days 8-12, in a hospital ward without intensive care unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to high dose IL-2 protocols, patient eligibility did not require pulmonary function tests and allowed serum creatinine up to 2 mg/dl.
  
  
  RESULTS
  Among 44 eligible patients, 57% (25) had their primary in place, 57% (25) had bone or visceral involvement, and only 4% (2) had lung as their only site of disease. The overall response rate in 43 response-evaluable patients was 16.3% [95% confidence interval (CI) 5.3 to 27.3], with three complete responses and four partial responses observed. The median survival was 13 months; nine patients remain alive at >23 months. The median duration of response is 36 months (range 11.5 to 48+ months). Toxicity was modest, consisting of typical cytokine-induced systemic symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13% of the 130 cycles.
  
  
  CONCLUSIONS
  This unique, reasonably well tolerated IL-2/IFN combination induced a modest response rate with a number of durable remissions. While the optimal IL-2-based regimen for the treatment of advanced renal cell carcinoma remains elusive, the present regimen should attract considerable interest. This is based on tumor activity very similar to high dose IL-2 in a patient population not as carefully selected for optimal organ function.
authors.affiliation: Edward Hines Jr VA Hospital, IL, USA. jclark@lumc.edu
authors.forename: J I
authors.initials: JI
authors.lastname: Clark
authors.forename: T M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: T M
authors.initials: TM
authors.lastname: Lestingi
authors.forename: S G
authors.initials: SG
authors.lastname: Fisher
authors.forename: P
authors.initials: P
authors.lastname: Sorokin
authors.forename: B
authors.initials: B
authors.lastname: Martone
authors.forename: M
authors.initials: M
authors.lastname: Viola
authors.forename: J A
authors.initials: JA
authors.lastname: Sosman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins