• Rate of new adenomatous polyp formation [ Designated as safety issue: No ]
• Effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa [ Designated as safety issue: No ]
• Side effects of treatment [ Designated as safety issue: Yes ]

• Rate of new adenomatous polyp formation
• Effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa
• Side effects of treatment

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eflornithine and sulindac may prevent colorectal cancer. It is not yet known whether eflornithine and sulindac are more effective than a placebo in preventing colorectal cancer.

PURPOSE: This randomized phase III trial is studying eflornithine and sulindac to see how well they work compared to a placebo in preventing colorectal cancer in patients with colon polyps.

OBJECTIVES:

• Compare the rate of new adenomatous polyp formation in patients with a history of adenomatous polyps of the colon treated with eflornithine and sulindac vs placebo.
• Correlate the effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa with the rate of new adenoma formation in these patients.
• Compare the rate of side effects in patients treated with these regimens.

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

Patients receive oral double placebo once daily for 4 weeks. Patients who are more than 70% compliant by pill measurement or self reporting are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral double placebo once daily.
• Arm II: Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

PROJECTED ACCRUAL: A total of 150 additional patients (124 randomized) will be accrued for this study within 18 months.

• Colorectal Cancer
• Precancerous/Nonmalignant Condition

• Drug: eflornithine
• Drug: sulindac

• McLaren CE, Fujikawa-Brooks S, Chen WP, Gillen DL, Pelot D, Gerner EW, Meyskens FL Jr. Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila Pa). 2008 Dec;1(7):514-21.
• Meyskens FL Jr, McLaren CE, Pelot D, Fujikawa-Brooks S, Carpenter PM, Hawk E, Kelloff G, Lawson MJ, Kidao J, McCracken J, Albers CG, Ahnen DJ, Turgeon DK, Goldschmid S, Lance P, Hagedorn CH, Gillen DL, Gerner EW. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila Pa). 2008 Jun;1(1):32-8.

DISEASE CHARACTERISTICS:

• History of ≥ 1 surgically resected adenomatous polyp of the colon measuring ≥ 3 mm within the past 5 years

• Screening colonoscopy performed within the past 6 months

  • All polyps must have been removed during colonoscopy, pathologically examined, and archived
• No prior surgical resection removing > 40 cm of the colon
• No personal or family history of familial polyposis or hereditary non-polyposis colon cancer

PATIENT CHARACTERISTICS:

Age

• 40 to 80

Performance status

• SWOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Hematocrit ≥ 35%
• WBC ≥ 4,000/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 2 times normal

Renal

• Creatinine ≤ 1.5 mg/dL
• Urine protein ≤ 1+*
• Urine casts 0-3*
• Urine WBC and RBC count 0-5 cells* NOTE: *By urinalysis

Gastrointestinal

• No history of inflammatory bowel disease

• No gastric or duodenal ulcers within the past 12 months

  • Gastric or duodenal ulcers that were adequately treated > 24 months ago are allowed
• No symptomatic gastric or duodenal ulcers

Other

• Not pregnant or nursing
• Negative pregnancy test
• Must have regional geographic stability over the next 36 months

• Pure tone audiometry evaluation normal

  • Patients with ≥ 20 dB of uncorrectable hearing loss (for age) of any 2 contiguous frequencies are not allowed
• No invasive malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, level I (or Breslow < 0.76 mm) cutaneous melanoma, Duke's A colon cancer, stage I cervical cancer, or stage 0 chronic lymphocytic leukemia
• No severe metabolic disorder
• No other significant acute or chronic disease that would preclude study participation
• No history of abnormal wound healing or repair
• No conditions that would confer risk of abnormal wound healing or repair
• No history of allergy to NSAIDs or eflornithine

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• No concurrent corticosteroids on a regular or predictable intermittent basis

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• Concurrent calcium supplements (≤ 1,000 mg/day) allowed
• Concurrent aspirin for cardiovascular prophylaxis (i.e., 81 mg/day) allowed
• Concurrent lipid-lowering drugs (i.e., high-dose statins) allowed
• No other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) on a regular or predictable intermittent basis
• No concurrent anticoagulants on a regular or predictable intermittent basis
• No concurrent treatment for gastric or duodenal ulcers