title: Lack of efficacy of low-dose subcutaneous recombinant interleukin-2 and interferon-alpha in the treatment of metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of subcutaneous immunotherapy using a combination of recombinant interleukin-2 (r-IL2) and interferon-alpha (IFN-alpha) for the treatment of patients with metastatic renal cell carcinoma (RCC).
  
  
  METHODS
  Initially a maximum of 45 patients with advanced RCC were to be included in the study, according to a Fleming three-stage procedure. To be included patients had to have measurable metastasis. Of a potential 45 patients with advanced RCC, 15 patients were included in the study (10 men and five women, mean age 51 years, range 25-69). From the first week of treatment r-IL2 was given subcutaneously on day 1 to 5, at 18 x 10(6) units once a day and then 9 x 10(6) units once a day for the following 5 weeks. IFN-alpha was given three times a week for the last 5 weeks. Minimum follow-up was 6 months.
  
  
  RESULTS
  All patients initially underwent radical nephrectomy. Seven patients were found to have metastases at the time of diagnosis. All patients received ambulatory therapy, except for the first 5 days of treatment. Overall, 80% of the patients received more than 75% of the complete dose of r-IL2. One patient suffered toxicity greater than the World Health Organization (WHO) grade 2 (neutropenia). No patient had a complete or partial response, two patients had a minor response, two patients had stable disease and 11 patients had disease progression.
  
  
  CONCLUSIONS
  Subcutaneous r-IL2 and IFN-alpha had no beneficial effect on the first 15 patients and the study was discontinued, in accordance with the Fleming rules. The dose, administration and combination of r-IL2 and IFN-alpha may explain the lack of efficacy. Other studies have shown that low doses of r-IL2 are not effective and the superiority of the combination of r-IL2 and IFN-alpha has not been proven. Therefore, a high dose of r-IL2, in association with other cytokines, chemotherapy and adoptive immunotherapy, may be the only way to improve the response rate of metastatic RCC.
authors.affiliation: Department of Urology, Cochin Hospital, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Thiounn
authors.forename: C
authors.initials: C
authors.lastname: Mathiot
authors.forename: T
authors.initials: T
authors.lastname: Dorval
authors.forename: T A
authors.initials: TA
authors.lastname: Flam
authors.forename: E
authors.initials: E
authors.lastname: Tartour
authors.forename: V
authors.initials: V
authors.lastname: Mosseri
authors.forename: M
authors.initials: M
authors.lastname: Zerbib
authors.forename: W H
authors.initials: WH
authors.lastname: Fridman
authors.forename: B
authors.initials: B
authors.lastname: Debre
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2