title: The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480.
abstract: Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)].
  
  
  METHODS
  191 patients entered on CALGB 9480 had pretreatment plasma collected and centrally stored. Using a human IL-6 immunoassay, quantitative levels of IL-6 were measured in duplicate on 300 muL samples. The proportional hazard model was used to assess the prognostic significance of IL-6 in predicting overall survival.
  
  
  RESULTS
  Median IL-6 level for the cohort of 191 patients was 4.80 pg/mL. Survival time among patients with IL-6 levels less than or equal to the median was 19 months (95% CI, 17-22) compared with 11 (95% CI, 8-14) months for patients above the median (P = 0.0004). In multivariate analysis, adjusting on performance status, lactate dehydrogenase, and prostate-specific antigen level, the hazard ratio was 1.38 (95% CI, 1.01-1.89; P = 0.043) using the median level as a cut point. Furthermore, a cut point of 13.31 pg/mL revealed robust prognostic significance with a hazard ratio of 2.02 (95% CI, 1.36-2.98; P = 0.0005).
  
  
  CONCLUSIONS
  Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP.
authors.affiliation: Divisions of Urology and Medical Oncology, Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham, NC 2771, USA. georg033@mc.duke.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Shepard
authors.forename: Ben
authors.initials: B
authors.lastname: Sanford
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary*; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015850:Interleukin-6; D017430:Prostate-Specific Antigen