Chemoprevention clinical trials

Daidzein and genistein have been most intensively investigated because of their high levels of occurrence in soybean, a widely used animal feedstuff and a component of traditional Asian diets consumed daily in high quantities by Japanese [10] and Chinese populations [8, 11]. The consumption of products derived from soy has, therefore, been considered as the major dietary factor contributing to the lower rates of hormone-dependent diseases, including breast, prostate, and colon cancers and coronary heart disease, in many Asian countries [12-14]. Almost 10 years after Akiyama et al. [15] first identified genistein as a tyrosine protein kinase inhibitor [15], it was entered into clinical chemoprevention trials in 1996 [16, 17], followed by formal human trials as a treatment for acute lymphoblastic leukemia and breast cancer [18-20]. 

Armstrong, W.B. A.R. Kennedy X.S. Wan T.H. Taylor Q.A. Nguyen J. Jensen W. Thompson W. Lagerberg EL. Meyskens. Clinical modulation of oral leukoplakia and protease activity by bowman-birk inhibitor concentrate in a phase iia chemoprevention trial. Clin. Cancer Res., 2000,... 

Actinic keratoses were the first skin lesions to be treated topically with all-frans-retinoic acid. In various clinical trials, retinoids have been shown to be active in chemoprevention and treatment or prevention skin malignancies [2]. 

The agent currently being used clinically as a breast cancer chemoprevention agent is tamoxifen. In randomized trials of tamoxifen as an adjuvant treatment for breast cancer, women who received tamoxifen also were found to have a reduced incidence of contralateral primary breast carcinomas.16 A... 

Boone CW, Kelloff GJ and Maolone WE. 1990. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials a review. Cancer Res 50 2-9. 

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. 

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... 

Forman, M.R. et al.. The fluctuation of plasma carotenoid concentrations by phase of the menstrual cycle a controlled diet study. Am. J. Clin. Nutr., 64, 559, 1996. Lipkin, M., Summary of recommendations for colonic biomarker studies of candidate chemopreventive compounds in phase II clinical trials, J. Cell. Biochem., Suppl. 19, 94, 1994. 

Pasic TR, Heisey D, Love RR. Alpha-difluoromethylor-nithine ototoxicity. Chemoprevention clinical trial results. Arch Otolaryngol Head Neck Surg 1997 123(12) 1281-6. 

The 5a-reductase inhibitors have been discussed previously (see Benign Prostatic Hyperplasia results of the Prostate Cancer Prevention Trial (128) for finasteride showed a 25% relative risk reduction in prostate cancer in men aged 55 years or older, albeit at an increased risk of invasive tumors (129). The risk of invasive tumors may outweigh the benefit of these agents. The 5a-reductase inhibitors have not been proven to be effective as chemoprevention against clinically significant prostate cancer. 

---