Exisulind in Preventing Polyps in Patients With Familial Adenomatous Polyposis

Chemoprevention of Duodenal Polyps in Familial Adenomatous Polyposis

RATIONALE: Exisulind may be effective in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.

PURPOSE: Randomized phase II/III trial to determine the effectiveness of exisulind in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.

OBJECTIVES:

• Determine the ability of exisulind to inhibit growth and development of duodenal adenomas in patients with familial adenomatous polyposis.
• Determine the effect on apoptosis in polyp vs mucosal tissue in these patients when treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral exisulind 4 times daily.
• Arm II: Patients receive oral placebo 4 times daily. Treatment continues for 1 year.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• One of the following diagnosis:

  • Diagnosis of familial adenomatous polyposis

    • Prior total or subtotal colectomy

  • Attenuated adenomatous polyposis coli

    • May have colon intact

• 10-40 duodenal polyps from second portion to 10 cm distal to papilla of Vater

PATIENT CHARACTERISTICS:

Age:

• 18 to 80

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Platelet count at least 100,000/mm^3
• No active hematologic disease

Hepatic:

• AST and ALT less than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 1.5 times ULN
• No active hepatic disease

Renal:

• Creatinine less than 1.5 mg/dL
• No active renal disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active peptic ulcer disease
• No serious underlying medical or psychiatric illness that would preclude completion of the study or limit survival
• No prisoners or institutionalized patients
• No known allergy to sulindac or related compounds
• No active internal malignancy within the past 5 years
• No alcohol or drug abuse within the past 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Other:

• No prior non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates more than 10 days a month for the past 3 months
• No concurrent NSAIDs (e.g., mesalamine, olsalazine, azodisalicylate, salsalate, sulfasalazine)
• Aspirin for cardiac reasons allowed (81 mg/day or 325 mg twice/week)