A Trial of Low Dose Sulindac Combined With Eflornithine in Patients With Familial Adenomatous Polyposis (FAP)

Inclusion Criteria:

• Diagnosis of phenotypic Familial Adenomatous Polyposis (FAP) of the colorectum based on meeting the criteria in one of two groups: Group 1-Greater than 100 adenomatous colorectal polyps prior to age 40. Group 2-Greater than 10 adenomatous polyps and age <40 or greater than 25 polyps and age >40; combined with a dominant family history or genotype: More than 100 polyps in a first-degree relative; More than 25 polyps in 2 relatives in 2 generations, including a first-degree family member; Genetic diagnosis in a relative; Genetic diagnosis by in vitro synthesized truncated protein or similar assay.
• No colorectal surgery or prior colon surgery for polyposis at least 1 year prior (total abdominal colectomy with ileal-rectal anastomosis, or total proctocolectomy with ilea pouch-anal reconstruction.

• Baseline endoscopy

  1. If no prior colorectal surgery, at least 3 polyps in a cluster each ≥ 2 mm in diameter; or
  2. If rectum is in situ and to be assessed, baseline rectal segment endoscopy documenting 3 or more rectal polyps each at least 2 mm in diameter in a defined cluster and/or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of rectum
  3. If ileal pouch neo-rectum is in place, 3 or more pouch polyps in a cluster ≥ 2 mm in diameter, or at least 6 polyps, ≥ 2 mm in diameter, in the distal 10 cm of pouch.
  4. Clinical/pathological grading of duodenal polyps will utilize the Spigelman Classification.
• Hematopoietic: no significant hematologic dysfunction; WBC ≥3,000/mm3; platelet count ≥100,000/mm3; hemoglobin ≥10g/dL; no known or prior clinical coagulopathy.
• Hepatic: bilirubin ≤ 1.5 times ULN; AST and ALT ≤ 1.5 times ULN; Alkaline phosphatase ≤ 1.5 times ULN.
• Renal: No significant renal dysfunction; creatinine ≤ 1.5 times ULN.
• Hearing: no clinically significant hearing loss that affects everyday life.
• Not pregnant or nursing.
• Negative serum pregnancy test if female of child-bearing potential.
• Absence of gross blood in stool.
• Fertile patients must use effective contraception.
• Stool occult blood either negative or minimal (1+).
• No prior hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; no NSAID associated symptoms of gastritis.
• No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated successfully with antibiotics (as documented by an endoscopy.
• No invasive malignancy within the past 5 years except stage I or II colon or rectal cancer or resected nonmelanomatous skin cancer.
• No other significant medical or psychiatric problems that would preclude study participation.
• No chronic adrenocorticosteroids.
• No prior pelvic irradiation.
• At least 3 months since prior investigational agents.
• Patients may not be receiving or plan to receive corticosteroids.
• Concomitant NSAID use outside this study may not exceed 4 days per month.
• Use of 81 mg daily aspirin or 650 mg aspirin not more than once a week.
• No concurrent warfarin, fluconazole, or lithium.
• Must be willing and able to sign informed consent.

Exclusion Criteria:

• High Risk for cardiovascular disease including clinical diabetes mellitus (Type I or II) requiring glycemic medications; Prior personal history of cardiovascular disease or, two or more of the following - hypertension or use of anti-hypertensive medications, hyperlipidemia or use of lipid-lowering medications or current smoker.
• Hearing loss that affects everyday life and or for which a hearing aid is required.