Epidemiologic and scientific research indicates that diet, lifestyle, and other modifiable factors have a significant influence on the risk of developin colorectal cancer (CRC). However, the influence of these interventions on the survival of patients with established CRC remains poorly understood. While randomized clinical trials (RCTs) demonstrate a significant survival advantage for stage III colon cancer patients who receive adjuvant fluorouracil-based chemotherapy, 35-40% of stage III patients receiving current adjuvant chemotherapy still develop cancer recurrence. Patients often seek to understand what, if any diet, lifestyle or supplement will reduce their chances of cancer recurrence. Moreover, how diet and lifestyle influence prognosis may depend, in part, on specific patient characteristics as well as molecular alterations in the tumor. We propose to address these gaps in knowledge within a NCI-sponsored, large, double-blind, placebo- controlled RCT assessing the influence of celecoxib on survival in stage III colon cancer patients who are concurrently receiving standard adjuvant chemotherapy (CALGB 80702). Beyond directly addressing the role of COX inhibition, the trial provides a) two longitudinal prospective assessments of diet, medication usage, and lifestyle habits; b) tumor specimens to examine how exogenous factors interact with specific molecular alterations; c) prospectively collected blood and germline DNA; and d) extensive data on cancer recurrence, mortality, and treated-related toxicity. Since pathologic stage, performance status, post-operative therapy and follow-up are carefully defined in this trial, residual confounding by disease and treatment characteristics should be minimized. In this application, we propose to examine the influence celecoxib and inflammation (Aim 1), and relevant effect modifying pathways (Aim 2) on the risk of cancer recurrence, mortality, and treatment-related toxicity.
Each aim extends current knowledge in these areas. Beyond the aforementioned hypotheses, this cohort will allow for the rapid examination of future hypotheses as they emerge. Ultimately, the proposed work seeks to improve our understanding of CRC biology, identify interventions that can improve patient survival, and, with the extensive clinical pathologic, genomic, and biomarker data available for analysis, inform clinicians how to maximally utilize these interventions to improve clinical care.
While considerable evidence supports the role of diet and lifestyle on the risk of developing colorectal cancer, the effect that these factors play on the survival of patients with established colorectal cancer is largely unknown. Using the resources of a large clinical trial, we propose to define the influence of these factors on patient survival o provide valuable information on colorectal cancer biology and offer meaningful interventions to improve patient outcomes.
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