Medical Management

Prophylactic resection of target organs is usually performed as treatment for familial tumours. However, it should be preferable in preventing the develop ment of tumours thereby ensuring a better functional result for the patient and a better quality of life. Although cancer prevention has been a matter of debate for many years, an effective and safe strategy has not yet been established. Since the first report by Kudo about the ability of indomethacin in preventing chemically induced colon cancer in rats [30], many authors reported the low incidence of CRC in people taking aspirin for a long time [31, 32]. In 1983, Waddell and Loughry observed a significant reduction in rectal polyps in four patients with FAP who took NSAIDs on a regular basis for pain relief [33].

Successive studies reported that sulindac decreases polyps in FAP and that cyclooxygenase 2 (COX-2), which is not expressed in normal mucosa, is largely expressed in colonic adenomas and cancerous tissue [34, 35] with a large amount of proneoplastic effects such as resistance to apoptosis via an increased level of the Bcl-2 protein [36], increased cell migration and invasion due to an over-expression of metallopro-teinases [37] and increased levels of angiogenic factors [38].

This data promoted a lot of interest about the therapeutic use of the new generation of the COX-2 inhibitors, which are more effective and clinically safer in comparison with other NSAIDS. Recent studies have noted the role of the COX-2 inhibitors presenting evidence of its abilities in reducing the amount and size of polyps, preventing the occurrence/recurrence of colorectal adenomas and cancer and counter-regulating angiogenesis in CRC liver metastases [39-41]. Therefore, once the efficacy of the COX-2 inhibitors is verified, what then should be the role of medical therapy in this complex disease?

There is no doubt about the supremacy of surgery as the only effective option for treating patients with FAP in a radical way. However, considering the risk of tumour should the relatives be diagnosed as carriers of a high-risk mutation, and the risk of new adenomas in the rectum should an ileo-rectal anastomoses be performed, anti-COX-2 drugs represent a good therapeutic option, but clinical data do not authorise their wide use outside of clinical trials.

In spite of all that, the efficacy shown in previous studies using sulindac was not confirmed and the National Cancer Institute in the United States is currently enrolling patients with FAP for a new clinical study of a combination therapy with celecoxib, eflorinithine (an ornithine decarboxylase inhibitor) or a placebo [42].

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