Table 3.

Non-randomized clinical trials of lower gastrointestinal tract chemoprevention in FAP patients

Ref.#	First author	Patients	Patient characteristics	Treatment regimen	Duration	Outcome	Side effects
[17]	Cruz-Correa	12	All patients had previous colectomy with IRA.	Sulindac mean dosage of 158 mg daily	14–98 months	At 12 months, 74% reduction of polyp number (p = 0.02). Significant reduction of high-grade adenomas (p = 0.004). One patient developed stage III rectal cancer after 35 months	Rectal mucosal erosions in six patients.
[21]	Waddell	10	Four patients had intact colons.	Sulindac 150 mg or 200 mg twice a day	12-85 months	Decrease or disappearance of polyps in all patients.	None reported
[22]	Rigau	7	Three patients had FAP. One patient had Gardner syndrome. One patient had non-familial adenomatous polyposis. Two patients had multiple hyperplastic polyposis.	Sulindac 200 mg twice per day	12–36 months	Reduction in number and size of polyps after 6 months in all patients. No development of carcinoma during follow-up.	None observed
[23]	Spagnesi	20	Fourteen patients had previous colectomy with IRA. Six had intact colons.	Sulindac 100 mg twice per day	60 days	Significant decrease in size and number of polyps (p < 0.01)	None reported
[24]	Ishikawa	6	Five patients had FAP. One patient had more than 30 colorectal adenomatous polyps.	Sulindac 300 mg daily	6 months	Three of six patients had reduction in polyp number.	One patient developed multiple ileorectal anastamotic ulcers despite reduction in dose. One patient had perforation of a gastric ulcer. One patient had oligospermia improved after stopping sulindac. One patient had subcutaneous abscess.
[25]	Winde	28	All patients had previous colectomy with IRA.	Sulindac 150 mg suppository twice a day with dose reduction	3–48 months	All patients had reduction in polyposis at 24 weeks.	No withdrawals due to adverse effects. Two patients had mild gastritis.
[26]	Tonelli	15	All patients had previous colectomy with IRA.	Sulindac 100 mg t wice per day	12–124 months	Significant regression of polyps after 6 months in all patients (p < 0.02). Polyposis increased. After a mean of 48.6 months, number and size of polyps increased again with statistical difference with baseline. One patient developed rectal cancer after 106 months.	One patient withdrew due to gastric bleeding after 49 months.
[27]	Fernandez-Lopez	29	All patient had previous colectomy with IRA.	Sulindac 150 mg twice a day	6 months	All patients had regression of polyps after 6 months except for one patient who eventually developed rectal cancer.	None reported
[28]	Guldenschuh	17	Seven patients had previous colectomy with IRA.	Sulindac 300 mg daily	4 months	Statistically significant decrease in number of adenomas (120 ± 112 to 28 ± 64, p = 0.007). Six months after cessation of therapy, number of adenomas increased to 48 ± 44.5.	None observed
[29]	Matsumoto	7	No patients had prior proctocolectomy.	Sulindac 100 mg three times per day	12 months	Protrusion index measured by double-contrast barium enema examination improved from 3.0 ± 1.1 to 1.1 ± 0.8/cm2 in distal colon (p < 0.02) and from 3.4 ± 2.4 to 0.9 ± 1.3/cm2 in proximal colon (p < 0.02).	None observed
[30]	Hirota	8	All patients had previous colectomy with IRA.	Indomethacin suppository 50 mg once or twice per day	4–8 weeks	In six of eight patients, number of polyps decreased. Number of polyps increased after indomethacin discontinuation.	Tenesmus occurred in one patient after suppository insertion.
[31]	Akasu	7	All patients had prior colectomy with IRA	Indomethacin sustained- release 75 mg–100 mg daily	81–345 days	Reduction of rectal polyp number seen in all patients (p = 0.023). Increase in size and number of rectal polyps after cessation of treatment in six patients after a median of 373 days.	Two patients had anaemia due to lower intestinal ulcers and treatment discontinued.
[50]	Dolara	7	All patients had previous colectomy with IRA.	Nimesulide 2 mg/kg per day	2.5 months	No change in mucosal proliferation by biopsy	One patient had generalized oedema and muscle pain.
[51]	Hallak	8	Five patients had previous colectomy with IRA.	Rofecoxib 25 mg daily	18–30 months	Reduction in polyp formation from 15.1 ± 11.7 to 6.0 ± 5.8 after 12 months (p = 0.002) and further decrease to 1.6 ± 1.6 at end of follow-up (p = 0.001).	No major side effects
[40]	van Stolk	18	All patients had previous colectomy with IRA.	Sulindac sulfone 200 mg, 300 mg, or 400 mg daily	6 months	No significant decrease in polyp number or cellular proliferation.	Reversible hepatotoxicity noted in eight of 18 patients.
[94]	Cruz-Correa	5	Four patient had previous colectomy with IRA and one patient had previous proctocolectomy with IPAA	Curcumin 480 mg and quercetin 20 mg three times per day	3–9 months	Decrease in rectal and ileal polyp number by 60.4% (p = 0.043) and size by 50.9% (p = 0.039) from baseline.	One patient had self-limited diarrhoea and, another patient reported mild nausea and sour taste with treatment.