title: Carbonic anhydrase IX expression is associated with improved outcome of high-dose interleukin-2 therapy for metastatic renal cell carcinoma.
abstract: OBJECTIVE
  The objectives of this study were to evaluate treatment responses to high-dose interleukin-2 (HD IL-2) in patients with metastatic renal cell carcinoma (mRCC) and assess correlation between responses and prognostic factors, such as histology, site of metastatic disease, prior treatment, prior nephrectomy, and carbonic anhydrase IX (CAIX) expression.
  
  
  METHODS
  A retrospective analysis was performed on all mRCC patients treated with HD IL-2 between 1996 and 2006 at the University of Minnesota Medical Center in Minneapolis, Minnesota, USA. A cycle of HD IL-2 consisted of 600,000 U/kg given once every 8 hours for 14 doses. Cycles were repeated until disease progression or intolerable toxicities developed. CAIX expression and staining intensity were evaluated on available primary tumor tissue.
  
  
  RESULTS
  Forty-seven patients with mRCC were identified. Of the 107 cycles of therapy that were given, 97.1% of patients received only two cycles of therapy. Complete response and partial response were seen in 3 (6%) and 15 (32%) patients, respectively. The overall disease control rate was 42.6%. The longest durable CR was 72 months and the shortest was 45 months. The median time to disease progression in patients with a CR or PR was 12 months. Patients with a Memorial Sloan-Kettering Cancer Center prognostic score of '1' were two times more likely to progress after two cycles than patients with a score of '0'. No response was observed in patients whose tumors were negative for CAIX by immunoperoxidase staining.
  
  
  CONCLUSIONS
  HD IL-2 is a reasonable option for first-line therapy for selected patients with mRCC. Patients with tumors negative for CAIX may not benefit from HD IL-2 therapy. Further research is necessary to define patients with a higher likelihood of disease response to this therapy.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, MMC 480, Minneapolis, MN 55455, USA. dudek002@umn.edu
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Yee
authors.forename: Juan C
authors.initials: JC
authors.lastname: Manivel
authors.forename: Rachel
authors.initials: R
authors.lastname: Isaksson
authors.forename: Heidi O
authors.initials: HO
authors.lastname: Yee
mesh_terms: D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000556:secondary / Q000628:therapy*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D007376:Interleukin-2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases