title: C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer: results from the ASCENT trial.
abstract: BACKGROUND
  Studies of cancer risk and molecular carcinogenesis suggest a role for inflammation in cancer development and progression. The authors sought to determine whether specific blood proteins associated with inflammation predict for outcomes in men with metastatic androgen-independent prostate cancer (AIPC) who are initiating docetaxel-based chemotherapy.
  
  
  METHODS
  Baseline plasma samples were stored (-80 degrees C) from 160 of 250 patients enrolled in the AIPC Study of Calcitriol ENhancing Taxotere (ASCENT) trial, a randomized, placebo-controlled trial comparing weekly docetaxel plus high-dose calcitriol with weekly docetaxel. Multiplex immunoassays measured 16 cytokine, chemokine, cardiovascular, or inflammatory markers. The Cox proportional hazards model was used to assess associations between baseline biomarkers, clinical characteristics, and survival. Logistic regression was used for analyses of associations with prostate-specific antigen (PSA) decline.
  
  
  RESULTS
  C-reactive protein (CRP) was found to be significantly predictive of a shorter overall survival (hazards ratio [HR] of 1.41 for each natural logarithm [ln] [CRP] increase; 95% confidence interval [95% CI], 1.20-1.65 [P < .0001]). When CRP (continuous) was entered into a multivariate model using 13 baseline clinical variables, only elevated CRP remained a significant predictor (P < .0001) of shorter overall survival. When categorized as normal (<or=8 mg/L) or abnormal (>8 mg/L), elevated CRP was found to be a significant predictor of shorter overall survival (HR of 2.96; 95% CI, 1.52-5.77 [P = .001]), as was hemoglobin (P = .007). Elevated CRP was also associated with a lower probability of PSA decline (odds ratio of 0.74 for each ln(CRP) increase; 95% CI, 0.60-0.92 [P = .007]). CONCLUSIONS.: Elevated plasma CRP concentrations appear to be a strong predictor of poor survival and lower probability of PSA response to treatment in patients with AIPC who are receiving docetaxel-based therapy.
authors.affiliation: Division of Hematology & Medical Oncology, Oregon Health & Sciences University, Portland, OR 97239, USA. beert@ohsu.edu
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.forename: Alshad S
authors.initials: AS
authors.lastname: Lalani
authors.forename: Stella
authors.initials: S
authors.lastname: Lee
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Eilers
authors.forename: John G
authors.initials: JG
authors.lastname: Curd
authors.forename: W David
authors.initials: WD
authors.lastname: Henner
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ryan
authors.forename: Peter
authors.initials: P
authors.lastname: Venner
authors.forename: J Dean
authors.initials: JD
authors.lastname: Ruether
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D002117:Calcitriol / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D010919:Placebos; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002120:Calcium Channel Agonists; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D002097:C-Reactive Protein; D017430:Prostate-Specific Antigen; D002117:Calcitriol