Phase I Clinical Study of Folate

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Healthy persons at increased risk for colorectal neoplasia due to 1 of the following
reasons:

- Personal history of colorectal adenomatous polyps

- Family history of colorectal adenoma or adenocarcinoma

- No history of multiple family members with colorectal neoplasia that is suggestive of
dominant hereditary neoplasia

PATIENT CHARACTERISTICS:

Age

- 40 to 72

Performance status

- Ambulatory

Life expectancy

- At least 6 months

Hematopoietic

- No excessive bleeding or coagulation disorder

Hepatic

- ALT or AST ≤ 2 times upper limit of normal

- No unexplained elevated alkaline phosphatase

Renal

- Creatinine ≤ 2.0 mg/dL

Cardiovascular

- Homocysteine concentration ≤ 17um/L

- No sustained blood pressure > 150/95 mm Hg for 3 consecutive readings

Other

- Vitamin B_12 ≥ 250 pg/mL

- Folate level ≤ 20 mg/dL

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 weeks after study
participation

- No intestinal malabsorption or inflammatory bowel disease

- No prior malignancy except nonmelanoma skin cancer

- No calcium metabolism abnormalities or predisposing conditions, such as
hyperparathyroidism

- No untreated hyperthyroidism

- No untreated insulin-requiring diabetes mellitus

- No daily alcohol intake > 2 ½ shot glasses of whiskey or three 8 ounce glasses of
beer or wine

- No other serious illness that might limit life expectancy to < 6 months

PRIOR CONCURRENT THERAPY:

Biologic therapy

- None

Chemotherapy

- None

Endocrine therapy

- No concurrent hormone replacement therapy, including oral, transplanted, or injected
contraceptives

- Concurrent thyroid hormone replacement is allowed as long as the patient is euthyroid
for 3 months

Radiotherapy

- None

Surgery

- No prior gastrointestinal surgery, including gastrectomy or small or large bowel
resections

- Prior appendectomy or surgery of the esophagus allowed

Other

- More than 3 months since regular ingestion of ≥ 650 mg per day of aspirin (≥ 2
tablets of 325 mg regular strength OR > 1 tablet of 500 mg extra strength aspirin)

- More than 3 months since regular daily ingestion of nonsteroidal anti-inflammatory
drugs

- At least 1 month since vitamin, mineral, or herbal supplementation

- No other concurrent vitamin, mineral, or herbal supplementation

- No concurrent anticoagulants

- No concurrent sterol-binding resins (i.e., cholestyramine)

- No other concurrent investigational drugs or medications that might alter rectal
mucosal proliferation, folate metabolism, or renal/hepatic impairment

- No concurrent weight control medications

- No concurrent supplemental folate preparations containing > 400 mcg of folic acid per
day

- No concurrent lipid-lowering medications

- The following concurrent statin drugs are allowed provided patient has been
taking a stable dose for ≥ 1 month:

- Atorvastatin 10 or 20 mg/day

- Fluvastatin 20 or 40 mg/day

- Lovastatin 10 or 20 mg/day

- Pravastatin 10 or 20 mg/day

- Simvastatin 5 or 10 mg/day