Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 5, 2004
Presenter: B. Chakravarthy
Presenter's Affiliation: Vanderbilt University
Type of Session: Scientific
Manipulation of arachidonic acid metabolism via the cyclooxygenase-2 (COX-2) pathway is an active area of oncology research. Studies have established that COX-2 leads to tumor growth via prostaglandin E2 (PGE2) production and vascular endothelial growth factor (VEGF) induction. Studies have also demonstrated that selective blockade of COX-2 can improve the anti-tumor efficacy of radiation therapy and chemotherapy. Furthermore, the use of COX-2 inhibitors has been found to reduce colon polyp formation in patients with familial adenosis polyposis (FAP). Stemming from this pathophysiologic observation with colon adenoma cells, the investigators of this trial sought to explore the efficacy of COX-2 inhibition in patients with clinically resectable rectal cancer. The COX-2 inhibitor was celecoxib, and it was tested alone as well as in combination with chemoradiation.
Materials and Methods
Attempts at optimizing cancer treatments continue to investigate and incorporate "targeted agents" as part of a multimodality approach. These agents focus on various pathways with known involvement in tumor growth and proliferation. Selective inhibition of the COX-2 enzyme process is an example of this, and this important phase II study from Vanderbilt University offers promising data on the efficacy of COX-2 inhibition in achieving meaningful pathologic tumor responses for resectable rectal cancer patients. Furthermore, the data shown here introduce a new, reliable, and easily attainable biomarker, such as urinary levels of a COX-2 pathway metabolite, to help follow and predict a given patient's response to treatment. Whether or not such a marker could actually help avoid surgery altogether in that subset of patients who are predicted to have a pathological complete response based on the biomarker remains hypothetical at this time. However, the potential use of biomarkers to custom-tailor treatment for certain patients (ie: those who might not be able to tolerate an extensive surgical procedure) makes further study of this arena very important. and worthwhile.