title: A low-dose combination therapy of interleukin-2 and interferon-alpha is effective for lung metastasis of renal cell carcinoma: a multicenter open study.
abstract: BACKGROUND
  To confirm the usefulness of a combination therapy of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) against metastatic renal cell carcinoma, the recommended dose of IFN-alpha to use in combination with low-dose IL-2 was determined (phase 1). Efficacy and safety at this dose was evaluated (phase 2).
  
  
  METHODS
  In phase 1, the dose of IL-2 was fixed at 0.7 x 10(6) Japan reference unit (JRU)/person for 5 days a week. The dose of IFN-alpha was increased from 3 x 10(6) IU for 3 days a week (level I) to 6 x 10(6) IU for 3 days a week (level II) and to 6 x 10(6) IU for 5 days a week (level III).
  
  
  RESULTS
  In phase 1, 10 patients were registered, with 9 (3 at each level) able to be evaluated. Because grade 3 and grade 4 neutropenia were observed at level III in 1 patient each, level II was found to be the recommended regimen. The response rate in phase 1 was 44.4% (4/9). In phase 2, 46 patients were registered, with a response rate in 37 patients, classified as per protocol set (PPS), of 21.6% (8/37). Toxicities observed were primarily flu-like symptoms due to cytokines, and gastrointestinal symptoms. Leukocyte abnormalities were observed, but they were milder and tolerable.
  
  
  CONCLUSIONS
  In the 46 patients evaluated in phase 1 and phase 2, the response rate was 26.1% (12/46), being highest in 38.7% (12/31) of those who were nephrectomized, and with only lung metastases.
authors.affiliation: Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 2-1-1 Amakubo, Tsukuba 305-0005, Japan. akazah@md.tsukuba.ac.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Onishi
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kinouchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015996:Survival Rate
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2