C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer (AIPC): Results from the ASCENT trial

Autor: A. S. Lalani, K. N. Chi, Tomasz M. Beer, W. D. Henner, P. M. Venner, Julie N. Graff, Ascent Investigators, S. Lee, J. G. Curd, J. D. Ruether, Christopher W. Ryan
Rok vydání: 2007
Předmět:
Zdroj: Journal of Clinical Oncology. 25:5074-5074
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2007.25.18_suppl.5074
Popis: 5074 Background: Concentrations of blood proteins such as PSA, hemoglobin (HGB), and LDH are associated with survival in men with AIPC. We sought to identify additional blood proteins associated with prognosis in chemotherapy-treated AIPC patients. Methods: Baseline plasma samples were stored (-80°C) from 160 patients enrolled in the ASCENT trial, a randomized placebo-controlled phase 2 trial comparing weekly docetaxel plus DN-101, an oral high-dose formulation of calcitriol, to weekly docetaxel. Multiplex immunoassays measured 16 cytokine/chemokine or cardiovascular/inflammation markers including IL-1a, IL-1β, IL-2, IL-6, IL-8, IL-10, TNFa, MCP-1, EGF, VEGF, PAI-1, MMP-9, sE-Selectin, sICAM-1, sVCAM-1 and C-reactive protein (CRP). Cox’s proportional hazard model was used to assess association between baseline biomarkers and survival or skeletal-related event (SRE)-free survival, and logistic regression for PSA Working Group Criteria response. Results: Baseline characteristics were similar to those of the 90 patients without samples, except for age (mean 68.0 vs. 70.6 yrs) and HGB (12.8 vs. 12.2 g/dL). CRP was the only biomarker that significantly predicted shorter overall survival (HR 1.41, 95% CI 1.20–1.65, p < 0.0001). When CRP (continuous) was entered into a multivariate model using 13 baseline variables (including PSA, LDH, alkaline phosphatase, HGB, ECOG Performance Status, age) only elevated CRP remained a significant predictor (p 8 mg/L), elevated CRP was a significant predictor of shorter survival (HR 2.96 95% CI 1.52–5.77, p = 0.001) as was HGB (p=0.007). Elevated CRP was also associated with a lower probability of PSA response (OR 0.74, 95% CI 0.60–0.92, p = 0.007) and a shorter SRE-free survival (HR 1.30, 95% CI 1.15–1.48, p < 0.0001). Conclusions: Elevated levels of plasma CRP appear to be a strong predictor of poor survival and development of SREs in AIPC patients receiving docetaxel-based therapy. The use of CRP as a risk marker and its potential as a surrogate marker of treatment effect should be prospectively evaluated in future clinical trials in advanced prostate cancer. [Table: see text]
Databáze: OpenAIRE
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