OBJECTIVES:

• Compare the efficacy of eflornithine (DFMO) and sulindac vs placebo in modulating a panel of surrogate endpoint biomarkers (SEB) of particular relevance in colorectal neoplasia, including quantitative histopathology, uninduced apoptosis, proliferative (Ki67) and preneoplastic (CEA, sialyl-TN, p53, and bcl-2) features, and polyamine and PGE2 levels in patients with at least one previously resected colorectal adenoma.
• Determine the relationship between the modulation of SEB in flat mucosa and the development of interval incident colorectal adenomas in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to aspirin use (yes vs no) and participating center.

Patients receive oral placebo daily for the first 4 weeks. Patients who are compliant and take the placebo 5 to 7 days each week are randomized to one of two treatment arms.

• Arm I: Patients receive oral sulindac and oral eflornithine (DFMO) daily.
• Arm II: Patients receive oral placebo daily. Treatment continues for 3 years in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: Approximately 240 patients (120 per treatment arm) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• At least 1 prior resected colorectal adenoma within the past 5 years

  • At least 3 mm in size
• No personal or family history of familial adenomatous polyposis

PATIENT CHARACTERISTICS:

Age:

• 40 to 80

Performance status:

• SWOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Hematocrit at least 35%
• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• AST and ALT no greater than 2 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL
• No greater than 1+ protein, 0-3 casts, and 0-5 WBCs and RBCs in urine

Gastrointestinal:

• No requirement for special diet or additives
• No diet that would preclude taking study medications
• No gastric or duodenal ulcer within the past year
• No inflammatory bowel disease

Other:

• No more than 20 dB hearing loss for age at any frequency
• No prior or concurrent invasive cancer within the past 5 years except nonmelanomatous skin cancer, melanoma in situ, stage I cervical cancer, stage I colon cancer, or stage 0 chronic lymphocytic leukemia
• No severe metabolic disorder or other acute or chronic diseases
• No history of or predisposition to abnormal wound healing or repair
• No allergies to nonsteroidal anti-inflammatories or eflornithine
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No concurrent chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent nonsteroidal anti-inflammatories or anticoagulants administered on a regular or predictable intermittent basis
• No concurrent aspirin greater than 81 mg per day or 325 mg twice a week for cardiovascular disease prophylaxis
• No concurrent calcium supplements greater than 500 mg/day