Polyp Prevention Trial

In a pooled analysis (88) of three studies (Wheat Bran Fiber Trial Polyp Prevention Trial Polyp Prevention Study) subjects with colorectal adenoma and Se levels in the highest quartile (median 150 ng/ml ) had significant lower odds of developing new adenoma compared with those in the lowest quartile (median I 13 ng/mL),... 

Lanza E, Yu B, Murphy G et al. (2007) The polyp prevention trial continued follow-up study no effect of a low-faL high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization. Cancer Epidemiol Biomarkers Prev 16 1745-1752... 

Bobe G, Murphy G, Albert PS, et al. Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial. Int ] Cancer. 2012 130(7) 1649—1659. 

Anti-neoplastic activity of UDCA was demonstrated first in the context of ulcerative colitis-associated colorectal carcinogenesis. Subsequently, encouraging (but not definitive) results have been obtained in clinical trials of UDCA for prevention of sporadic colorectal adenoma recurrence, which should prompt further evaluation of UDCA for polyp prevention, particularly given its excellent safety profile compared with other candidate chemoprevention agents such as the nonsteroidal anti-inflammatory drugs. 

On September 30, 2004, rofecoxib was withdrawn from the worldwide market by the manufacturer, based on results obtained from the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial. For those on rofecoxib 25 mg daily compared with placebo, risk for confirmed cardiovascular events, including myocardial infarction and stroke, was approximately doubled, beginning after 18 months of treatment. 

MacLennan, R., Macrae, F., Bain, C., Battistutta, D., Chapuis, P., Qratten, H., Lambert, J., Newland, R.C., Ngu, M., Russell, A. et al.. The Australian Polyp Prevention Project randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas, J. 

The Polyp Prevention Study Group. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. N Engl J Med 1994 331(3) 141 7. 

There are no published RCTs of vitamin C alone in primary prevention, but data from the small number of trials of vitamin C in combination with other nutrients have not provided any support for a role for high-dose vitamin C supplementation in cancer prevention (Table 3). The Linxian trial found no significant effect of supplementing Chinese men and women with 120 mg vitamin C and 30 pg molybdenum daily for 5 years on the risk of cancers of the oesophagus or stomach. The Polyp Prevention Study, a trial of 864 patients with previous adenoma, found no effect of either /3-carotene or a combination of vitamins E and C (1000 mg) on the incidence of subsequent colorectal adenomas. The Heart Protection Study also found no beneficial effects of supplementation with these three vitamins on cancer mortality. However, trials have generally... 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

Another potential use for these drugs was to prevent the formation of adenomatous polyps in patients with a history of colorectal adenomas. Rofecoxib and celecoxib were both tested in this disease. It was the results of this test that prompted Merck to withdraw their drug from the market since this study clearly established the increased risk of cardiovascular events when rofecoxib is used. The results were sufficiently strong to have the safety monitoring board reevaluate the data for a similar trial with celecoxib. On the basis of these data the study with celecoxib was also terminated. Interestingly, another study in which celecoxib was used to prevent polyp formation resulted in no increase in cardiovascular events. The only difference between the two studies was that in the latter case celecoxib was given once a day whereas in the prior study celecoxib was administered at the same dose but twice a day. How this difference in treatment schedules affected the toxic outcomes is unknown at the present time. 

A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps. Cancer Res., 48, 4701, 1988. 

Gardner FJ, Konje JC, Bell SC, Abrams KR, Brown LJ, Taylor DJ, Habiba M. Prevention of tamoxifen induced endometrial polyps using a levo-norgestrel releasing intrauterine system long-term follow-up of a randomised control trial. Gynecol Oncol 2009 114(3) 452-6. 

A large number of clinical intervention studies have examined the effect of supplemental p-carotene on intermediate cancer endpoints, as shown in Table 1. The results of these trials indicate that supplemental p-carotene consistently results in regression of oral precancerous lesions (oral leukoplakia, oral dysplasia), and a decreased frequency of micronucleated buccal mucosal cells. While many of the trials of oral precancerous endpoints were not placebo-controlled, and thus somewhat difficult to interpret because spontaneous regression can occur, those that were placebo-controlled nonetheless demonstrated significant benefit to p-carotene relative to placebo. From Table 1 it appears that the chemopreventive efficacy of p-carotene varies by site, with evidence for efficacy in the oral cavity and possibly esophagus, mixed evidence in cervix and lung, and convincing evidence of a lack of efficacy in the prevention of recurrent colorectal polyps. 

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