Table 2.

Randomized, placebo-controlled clinical trials of lower gastrointestinal tract chemoprevention in FAP patients

Ref. #	First author	Patients	Patient characteristics	Treatment regimen	Duration	Outcome	Side effects
[16]	Giardiello	22	All patients had history of polyposis. 18 patients had intact colons. Four patients had undergone subtotal colectomy with ileorectal anastamosis.	Sulindac 150 mg twice a day	9 months	At nine months, sulindac group had decrease in number of polyps by 56% (p = 0.014) and size of polyps by 65% (P < 0.001). 3 months after the discontinuation of sulindac, there was increase in number and size of polpys.	None observed
[18]	Labayle	10	All patients had history of colectomy and ileorectal anastamosis.	Sulindac 100 mg three times a day	4 months	Statistically significant decrease in rectal polyps in sulindac vs. placebo (P < 0.01). Recurrence of polyps after discontinuation of sulindac.	None observed
[19]	Nugent	24	All patients had advanced duodenal polyposis and previous prophylactic colectomy.	Sulindac 200 mg twice a day	6 months	Rectal polyps improved in five of seven patients (p = 0.01) taking sulindac. Duodenal polyps improved in five of 12 patients (p = 0.12) taking sulindac.	One patient stopped sulindac for indigestion within 6 weeks.
[20]	Giardiello	41	Genotypically affected FAP patients without polyposis at time of randomization.	Weight 20–44 kg – Sulindac 75 mg twice a day. Weight >44 kg – Sulindac 150 mg twice a day	48 months	No significant differences in the mean number or size of polyps between sulindac and placebo. Five of 21 withdrawn from sulindac group and six of 20 withdrawn from placebo group.	Few adverse effects. One withdrawn from study for possible drug-induced persistent neutropenia.
[46]	Steinbach	77	All patients had five or more polyps at randomization. Twenty-five had intact colons.	Celecoxib 100 mg twice daily or 400 mg twice daily	6 months	Mean number of colorectal polyps reduced by 28% (p = 0.003), rectal polyps reduced by 22.5% (p = 0.01), and polyp burden reduced by 30.7% (p = 0.001) in the high-dose celecoxib group compared to placebo.	No significant difference in adverse events among low-dose celecoxib, high-dose celecoxib, and placebo. One patient withdrew from study due to dyspepsia. Another patient withdrew due to acute allergic reaction. Another patient with prior psychiatric history committed suicide.
[47]	Lynch	18	All patients, aged 10 to 14 years-old, had APC mutations and/or adenomas with family history of FAP.	Celecoxib 16 mg/kg per day	3 months	Reduction in colorectal polyps by 44.2% (p = 0.01)	No significant difference in adverse events between celecoxib and placebo.
[48]	Higuchi	21	Thirteen patients had previous colectomy with IRA.	Rofecoxib 25 mg daily	9 months	At 9 months, 9.9% decrease in polyp number compared to placebo (p = 0.004) and reduction in polyp size compared to placebo (−16.2% versus 1.5%, p < 0.001).	No significant difference in adverse events.
[49]	Iwama	61	All patients had diagnosis of FAP as defined by 100 or more adenomas in the colon and rectum. Twenty-four patients had intact colons.	Tiracoxib 150 mg daily or 200 mg daily	26 weeks	No significant difference in polyp number or size noted between tiracoxib and placebo group	No difference in adverse events noted between tiracoxib and placebo group
[61]	Burn	206	All patients were young patients aged 10 to 21 years-old, who had confirmed FAP-associated APC mutation or high probability of carrying the mutation based on linked DNA markers or presence of mlutiple colonic polyps. All patients had intact colons.	Aspirin 300 mg twice a day and/or resistant starch 15 g twice a day	Median 17 months	No significant reduction in polyp count in the rectosigmoid colon with aspirin or resistant starch. Trend towards smaller size of largest polyp in aspirin compared to nonaspirin group (3.8 mm versus 5.5 mm, p = 0.09). Significant decrease in largest polyp size in aspirin group compared to nonaspirin if treated >1 year (3.0 mm versus 6.0 mm, p = 0.02).	No serious adverse effects recorded. One patient withdrew from aspirin/ resistant starch group due to persistent epistaxis.
[86]	West	55	All patients had previous colectomy with ileorectal anastamosis.	Eicosapentaenoic acid 1 g twice daily	6 months	Number of rectal polyps reduced by 22.4% (p = 0.012) and sum of polyp diameter reduced by 29.8% (p = 0.027).	No significant difference in adverse events between eicosapentaenoic acid and placebo.
[95]	Bussey	36	All patients had previous colectomy with ileorectal anastamosis.	Vitamin C 3 g daily	15–24 months	A non-significant trend towards reduction in rectal polyp number noted in vitamin C compared to placebo group at 9, 12, and 15 months.	None reported
[96]	DeCosse	58	All patients had previous colectomy with ileorectal anastamosis.	Vitamin C 4 g and Vitamin E 400 mg daily or grain fiber 22.5 g daily	4 years	No difference in rectal polyp number between Vitamin C/E group and placebo. Trend towards decrease in rectal polyp number in fiber group compared to placebo at 9 and 33 months.	Diarrhoea more frequent in fiber group (p < 0.05).
[98]	Thomas	25	All patients had previous colectomy with ileorectal anastamosis.	Calcium carbonate 1500 mg daily	6 months	No significant difference in rectal polyp number, progression, or distribution between calcium and placebo group.	None reported