title: Combined immunotherapy with low-dose IL-2 plus IFN-alpha for metastatic renal cell carcinoma: survival benefit for selected patients with lung metastasis and serum sodium level.
abstract: OBJECTIVE
  To clarify the survival benefit of immunotherapy for renal cell carcinoma patients with lung metastasis using low-dose interleukin-2 plus interferon-α, we examined survival outcomes and factors associated with prognosis.
  
  
  METHODS
  This was a multicenter prospective study. Nephrectomized renal cell carcinoma patients with lung metastasis were treated with interleukin-2 (0.7 × 10(6) unit, 5 days a week) and interferon-α (6 × 10(6) IU, 3 days a week) for the first 8 weeks, and then with both interleukin-2 and interferon-α, 2 or 3 days a week for 16 additional weeks.
  
  
  RESULTS
  Median follow-up period for 42 patients was 28.3 months (range: 4.2-43.8). Two-year overall survival rate was 82% and the probability of 3 year survival rate was 71%. Median progression-free survival was 10.4 months. While no difference was found in survival among patients assessed as complete response, partial response and no change, survival of patients assessed as NC or better was significantly better than those assessed as progressive disease (P < 0.0001). Furthermore, multivariate analyses identified pre-treatment serum sodium (P = 0.004) as an independent prognostic factor. The sodium level was also statistically associated with tumor response (p = 0.035). Patients with normal sodium level survived significantly longer (P = 0.0005) than those with low sodium level showing median survival of 12.2 months.
  
  
  CONCLUSIONS
  Combination immunotherapy with low-dose interleukin-2 plus interferon-α showed survival benefit for patients with lung metastasis whose tumor responded as no change or better. This combination immunotherapy could be beneficial for patients selected by metastatic organ and their pre-treatment serum sodium level.
authors.affiliation: Department of Strategic Investigation on Comprehensive Cancer Network, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan. akazah@med.rcast.u-tokyo.ac.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Zembutsu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012964:Sodium / Q000097:blood; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D012964:Sodium