Colorectal cancer accounts for more than 60,000 deaths per year. Despite improved surgical management of this disease, there has been little improvement in 5 year survival rates since the 1960s. Clearly, the development of new prevention strategies is of importance if we are to observe decreased death rates in the 21st century. Accordingly, the long- term goal of this proposal is to reduce the morbidity and mortality from colorectal cancer. To accomplish this goal, the following 3 clinical chemoprevention trials will be conducted in subjects at high risk for colorectal: . Project I: A two-armed stratified, randomized double blind placebo-controlled cancer control phase III trial of wheat bran fiber supplement in 950 subjects at high risk for adenomatous polyp recurrence. [3H]-thymidine labeling index in crypt organ culture of rectal mucosa will be measured as a secondary endpoint. . Project II: A two-armed stratified, randomized placebo- controlled cancer control phase IIb clinical trial of piroxicam, a prostaglandin synthesis inhibitor, in 100 subjects at high risk for adenomatous polyp recurrence.
The aim of this trial is to determine the lowest dose at which piroxicam routinely suppresses prostaglandin synthesis and colonic cell proliferation. Intermediate biologic and biochemical markers of cancer risk will be assessed serially, including measurement of PGE2, 6-KETO- PGF1alpha and thromboxane B2 levels and [3H]-thymidine labeling index in crypt organ culture. . Project III: Short-term dosage reduction phase IIa and two armed stratified, randomized placebo-controlled cancer control phase IIb clinical trials of difluoromethylornithine (DFMO) (a polyamine synthesis inhibitor). Primary endpoints are serial measures of polyamine metabolism and [3H]-thymidine labeling in crypt organ culture. The three Cores, Administration, Biometry and Services (Analytical, Nutrition, Adherence) provide the structure and expertise for successful execution of the clinical trials and associated laboratory research studies. A specialized Quality Assurance/Quality Control program further monitors each of the 3 clinical projects.
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