Chemoprevention: risk reduction with medical therapy of inflammatory bowel disease.
The ideal chemopreventative agent, in addition to being efficacious in the prevention of cancer, must be easily administered, affordable, safe, and well tolerated, with minimal side effects. In the past decade, a growing body of literature has emerged on the prevention of CRC in patients with long-standing CD and UC. The data are not definitive and consist almost exclusively of retrospective case-control and cohort studies rather than the more rigorous prospective RCTs. 5-ASA compounds have been most thoroughly studied, and most of the existing data support the use of 5-ASA in the prevention of CRC. Although the precise dose and duration are unclear, studies suggest that chronic systemic administration of 5-ASA at a dose of at least 1.2 g/d is most likely to be effective. A beneficial effect of folate, albeit not statistically significant, has been consistently shown in every study performed for this purpose. Folate supplementation, which is safe and affordable, should also be recommended for all patients with IBD, especially those taking sulfasalazine. UDCA has been shown to exert a protective effect in most studies on patients with UC and concomitant PSC. Because this patient population is at particularly high risk for CRC, it is advisable to consider UDCA in all patients with colitis complicated by PSC. For patients without PSC, sufficient data do not exist to recommend it for the purpose of cancer prevention. Five of the six corticosteroid studies have found a beneficial effect of systemic steroids, although most did not reach statistical significance. Regardless, given the frequent and serious adverse effects associated with chronic steroid use, systemic corticosteroids should not be prescribed for this indication. Budesonide, an oral corticosteroid with minimal systemic absorption, is a potential alternative, although it has not yet been studied as a chemopreventative agent. Similarly, until the long-term safety of chronic NSAID use can be demonstrated in patients with IBD, the role of NSAIDs in chemoprevention remains undefined. Although the data are conflicting, immune-modulating medications, such as AZA, do not seem to confer any reduction in the risk of dysplasia or CRC. The data on calcium supplementation and statin use are still too limited to endorse their use for the prevention of colitis-related CRC. Chemoprevention is an area that holds great promise in the reduction of morbidity and mortality associated with IBD. Further studies, including prospective trials when possible and cost-effectiveness analyses, need to be performed to develop an optimal strategy for the reduction of cancer risk in patients with IBD.
Chan
Erick P
EP
Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
Lichtenstein
Gary R
GR
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D016021:Epidemiologic Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy*; D040242:Risk Reduction Behavior; D012459:Salicylates / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D005938:Glucocorticoids; D012459:Salicylates