Abstract
Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of “chemoprevention” trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventive agents. Sulindac, largely by historical accident, has been the most extensively studied, and is widely considered the standard of care when a clinical decision to intervene medically is made. Newer trials are evaluating combinations of agents in order to take advantage of differing mechanisms of action, in the hope of achieving synergy, as no single agent predictably or completely suppresses adenoma growth. Some of these studies and other single-agent interventions are discussed, though an exploration of the various mechanisms of action is beyond the scope of this paper. It is essential that future trials focus on the issue of “clinical benefit”, not simply because the US Food and Drug Administration has insisted on it, but because only real evidence-based advances can improve the standard of medical care for FAP patients. Hence my focus on issues of trial design and clinically relevant endpoints.
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References
Jasperson K, Burt RW (2015) The genetics of colorectal cancer. Surg Oncol Clin N Am 24:683–703
Half E, Arber N (2009) Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin Pharmacother 10:211–219
Kim B, Giardiello FM (2011) Chemoprevention in familial adenomatous polyposis. Best Pract Res Clin Gastroenterol 25:607–622
Waddell WR, Loughry RW (1983) Sulindac for polyposis of the colon. J Surg Oncol 24:83–87
Labayle D et al (1991) Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101:635–639
Giardiello FM et al (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328:1313–1316
Winde G, Gumbinger HG, Osswald H, Kemper F, Bunte H (1993) The NSAID sulindac reverses rectal adenomas in colectomized patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration. Int J Colorectal Dis 8:13–17
Cruz-Correa M, Hylind LM, Romans KE, Booker SV, Giardiello FM (2002) Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study. Gastroenterology 122:641–645
Debinski HS, Trojan J, Nugent KP, Spigelman AD, Phillips RK (1995) Effect of sulindac on small polyps in familial adenomatous polyposis. Lancet 345:855–856
Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK (1993) Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg 80:1618–1619
Seow-Choen F, Vijayan V, Keng V (1996) Prospective randomized study of sulindac versus calcium and calciferol for upper gastrointestinal polyps in familial adenomatous polyposis. Br J Surg 83:1763–1766
Bulow S et al (2004) Duodenal adenomatosis in familial adenomatous polyposis. Gut 53:381–386
Solomon SD et al (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352:1071–1080
Bresalier RS et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102
Steinbach G et al (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946–1952
Phillips RK et al (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860
Hallak A et al (2003) Rofecoxib reduces polyp recurrence in familial polyposis. Dig Dis Sci 48:1998–2002
Burn J et al (2011) A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. Cancer Prev Res (Phila) 4:655–665
Ishikawa H et al (2013) Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial. Cancer Med 2:50–56
Gerner EW, Meyskens FL Jr (2009) Combination chemoprevention for colon cancer targeting polyamine synthesis and inflammation. Clin Cancer Res 15:758–761
Meyskens FL Jr, Gerner EW (1999) Development of difluoromethylornithine (DFMO) as a chemoprevention agent. Clin Cancer Res 5:945–951
Lynch PM et al (2016) An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis. Gut 65:286–295
Cruz-Correa M et al (2006) Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 4:1035–1038
Bussey HJ et al (1982) A randomized trial of ascorbic acid in polyposis coli. Cancer 50:1434–1439
West NJ et al (2010) Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut 59:918–925
Giardiello FM et al (2002) Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 346:1054–1059
Lynch PM et al (2010) The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol 105:1437–1443
Lynch PM et al (2013) Global quantitative assessment of the colorectal polyp burden in familial adenomatous polyposis by using a web-based tool. Gastrointest Endosc 77:455–463
Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK (1989) Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 2:783–785
Taylor S, Slater A, Honeyfield L, Burling D, Halligan S (2006) CT colonography: effect of colonic distension on polyp measurement accuracy and agreement-in vitro study. Acad Radiol 13:850–859
Macari M, Green JC, Berman P, Milano A (1999) Diagnosis of familial adenomatous polyposis using two-dimensional and three-dimensional CT colonography. AJR Am J Roentgenol 173:249–250
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Lynch, P.M. Chemoprevention of familial adenomatous polyposis. Familial Cancer 15, 467–475 (2016). https://doi.org/10.1007/s10689-016-9901-9
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DOI: https://doi.org/10.1007/s10689-016-9901-9