C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer

Results from the ASCENT trial

Authors


  • Oregon Health and Sciences University (OHSU) and Dr. Beer have a significant financial interest in Novacea, a company that may have a commercial interest in the results of this research and technology. This potential conflict was reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council was implemented.

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°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 (≤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. Cancer 2008. © 2008 American Cancer Society.

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