Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 5074
© 2007 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Graff, J. Search for Related Content PubMed Articles by Graff, J.

Abstract

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

Oregon Health & Science University, Portland, OR; Novacea, Inc., South San Francisco, CA; Cross Cancer Institute, Edmonton, AB, Canada; Tom Baker Cancer Ctr-University of Calgary, Calgary, AB, Canada; British Columbia Cancer Agency, Vancouver, BC, Canada

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-1ß, 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<0.0001) of shorter survival. When categorized as normal (= 8 mg/L) or abnormal (> 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.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novacea Novacea Novacea Novacea

Abstract presentation from the 2007 ASCO Annual Meeting