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C-Reactive Protein Levels Predict Skeletal-Related-Event Survival in Men With Metastatic Androgen-Independent Prostate Cancer: Presented at EAU

By Chris Berrie

BERLIN, GERMANY -- March 26, 2007 -- Elevated plasma C-reactive protein (CRP) levels demonstrate a strong statistical correlation with shorter skeletal-related-event (SRE) survival with docetaxel-containing chemotherapy regimens in men with metastatic androgen-independent prostate cancer (AIPC).

This finding from a phase 2 retrospective analysis of a placebo-controlled trial by the ASCENT (AIPC Study of Calcitriol Enhancing Taxotere) investigators was presented here on March 21^st at the 22^nd Annual Congress of the European Association of Urology (EAU).

Bone metastases represent an important cause of morbidity in about 80% of men with advanced prostate cancer, according to coinvestigator Joseph Chan, MD, fellow in medicinal oncology, department of medicine, Oregon Health and Science University, Portland, Oregon, United States. Within 15 months, and despite chemotherapy, 30% to 40% of these patients will experience SREs,

Dr. Chan and his colleagues conducted their study to identify additional blood biomarkers that are associated with SRE-free survival in men with androgen-independent prostate cancer.

Within the ASCENT study (n = 250), 160 patients with AIPC provided plasma samples for this analysis. Sixteen potential biomarkers were monitored: IL-1alpha, IL-1beta, IL-2, IL-6, IL-8 and IL-10, TNFalpha, EGF, VEGF, MCP-1, sE-Selectin, s-ICAM-1, s-VCAM-1, tPAI-1, MMP-9, and CRP.

"The markers were analysed simultaneously by multiplex immunoassays using uniquely-labelled fluorescent microspheres conjugated to anticytokine capture antibodies," detailed Dr. Chan.

Patients were randomised to placebo or the calcitriol DN-101 45 mcg PO on day 1, followed by docetaxel 36 mg/m² IV on day 2, with this docetaxel dose repeated weekly for 3 of 4 weeks.

Baseline characteristics of these 160 patients included the following: median age, 68.0 years; Eastern Cooperative Oncology Group performance status 0/ > 0, 50.6%/ 49.4%; bone metastatic site, 88.8%; median PSA, 125 ng/mL; median haemoglobin, 12.8 g/dL; median lactate dehydrogenase, 209.5 U/L; and median alkaline phosphatase, 127 U/L.

Patients' SRE history included radiation therapy to bone (17.5%), pathological bone fracture (6.3%), spinal chord compression (5.6%), change in therapy due to bone pain (3.8%), and surgery to bone (2.5%); also, 89% had bone metastases at baseline, and 26% had suffered an SRE in the previous 12 months.

After Cox's proportional hazard modelling to assess the relationships between the baseline biomarkers and SRE-free survival, elevated CRP (P < .0001) and IL-2 (P = .0230), and lower MMP-9 (P = .0126) were the only biomarkers examined associated with shorter SRE-free survival.

Elevated CRP (>8 mg/mL; n = 102) was also seen to be a significant predictor of shorter SRE-free survival (P = .009).

Dr. Chan noted that CRP is a readily measurable marker of inflammation, and that this finding is consistent with the hypothesis that inflammation is an important determinant of prostate cancer prognosis. When this is combined with the IL-2 and MMP-9 data, their study also provides further insight into the biology of tumour metastasis in bone.

This researcher was supported by Novacea Inc.


[Presentation title: C-Reactive Protein to Predict Risk of Skeletal Morbidity in Men With Androgen-Independent Prostate Cancer: Results From the ASCENT Trial. Poster Session 14, Abstract 261]

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