High CRP is linked to poor prostate ca survival

ORLANDO—Elevated levels of the inflammatory marker C-reactive protein (CRP) are associated with an increased risk of death in men with advanced prostate cancer, according to findings from a subanalysis of the ASCENT (AIPC Study of Calcitriol Enhancing Taxotere) trial, presented at the 2007 Prostate Cancer Symposium (abstract 220).

"This finding is consistent with the hypothesis that inflammation is an important determinant of prostate cancer treatment resistance and prognosis," said Tomasz M. Beer, MD, associate professor of medicine and director of prostate cancer research, Oregon Health & Science University Cancer Institute, Portland.

The finding also suggests that CRP testing, which is already available to assess cardiovascular disease risk, may also be useful in predicting survival in men with advanced prostate cancer, he said.

Inflammation has been linked to cancer progression and shorter survival in several types of cancer. Dr. Beer and his associates took blood samples from 160 men with advanced prostate cancer who were participants in the phase II ASCENT trial to examine the relationship between baseline inflammatory markers and patient outcomes. The trial compared docetaxel (Taxotere) with DN-101 (high-dose calcitriol, Asentar) vs docetaxel with placebo in men with metastatic androgen-independent prostate cancer (Beer et al: J Clin Oncol 25:669-674, 2007).

Dr. Beer explained that a confirmatory phase III ASCENT-2 trial is underway, after the phase II ASCENT study showed longer survival and a reduction in adverse events in the calcitriol arm, along with trends in favor of calcitriol with respect to PSA response.

The researchers looked at 16 inflammatory markers, including the interleukins, tumor necrosis factor-alpha, monocyte chemotactic peptide-1, epidermal growth factor, matrix metalloproteinase-9, vascular endothelial growth factor, soluble E-selectin, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and CRP.

CRP was the only biomarker that significantly predicted shorter overall survival. "After a median follow-up of 18.6 months, we found that having an elevated C-reactive protein level greater than 8 mg/L was associated with a nearly threefold increase in the risk of death," Dr. Beer said. Each doubling in the CRP level increased the risk of death by 27%. An elevated CRP was also associated with a lower probability of responding to docetaxel-based chemotherapy. For each doubling of the CRP, the response to docetaxel, as measured by PSA decline, decreased by 19%, he said.

These findings need to be confirmed in other studies, Dr. Beer said. If they are, he commented, "we will have a powerful new prognostic factor available to physicians and patients with advanced prostate cancer." The finding also opens up a new vista in which to investigate the role of inflammation in prostate cancer that is resistant to chemotherapy, he added.

Dr. Beer disclosed that he has a significant financial interest in Novacea, Inc., maker of Asentar.