OBJECTIVES:

• Compare celecoxib vs placebo in terms of preventing the development of new actinic keratoses in patients with actinic keratoses.
• Compare these treatment regimens in terms of inducing regression of actinic keratoses in these patients.
• Determine the safety of this drug in these patients.
• Compare the effect of these treatment regimens on potential surrogate end-point biomarkers in areas of actinic keratosis, sun-exposed skin, and non-sun-exposed skin and correlate these biomarkers with clinical outcome in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral celecoxib twice daily for 9 months in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral placebo as in arm I. Patients are followed at 2 months after completing treatment.

PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of Fitzpatrick skin types I, II, or III
• Sun-damaged skin with 10-40 actinic keratoses on the upper extremities (upper arms, forearms, and hands), neck, face, and scalp combined

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 125,000/mm^3
• Hemoglobin at least lower limit of normal
• No significant bleeding disorder

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 1.5 times ULN
• No chronic or acute hepatic disorder

Renal:

• Creatinine no greater than 1.5 times ULN
• BUN no greater than 1.5 times ULN
• No chronic or acute renal disorder

Gastrointestinal:

• No history of or active inflammatory bowel disease
• No active pancreatitis
• Not diagnosed with esophageal, gastric, pyloric channel, or duodenal ulceration within the past 30 days

Other:

• No history of keloid formation
• No known photosensitivity disorder
• No history of hypersensitivity or adverse reaction to sulfonamides, COX-2 inhibitors, salicylates, or other NSAIDs
• No other condition that would preclude study
• No other medical or psychosocial condition that would preclude study

• No other malignancy within the past 5 years except:

  • Carcinoma in situ of the cervix
  • Curatively excised nonmelanoma skin cancer
  • Stage 0 chronic lymphocytic leukemia
  • Any cancer for which the patient is currently without evidence of disease, has not been treated for tumor within the past 6 months, has no current or planned therapy, and has an expected disease-free survival of at least 5 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 30 days since prior systemic immunotherapy
• No concurrent immunotherapy

Chemotherapy:

• At least 3 months since prior topical fluorouracil (5-FU)
• At least 6 months since other prior topical chemotherapy
• No concurrent topical chemotherapy, including 5-FU
• No other concurrent chemotherapy

Endocrine therapy:

• At least 6 months since prior oral or IV corticosteroids for more than 2 consecutive weeks
• At least 6 months since prior inhaled or nasal corticosteroids for more than 4 weeks duration
• At least 14 days since prior topical corticosteroids
• At least 30 days since prior nasal corticosteroids (except mometasone)
• No concurrent oral or IV corticosteroids for more than 2 consecutive weeks during any 6 month period during study
• No concurrent inhaled or nasal steroids (except mometasone) for more than 4 weeks during any 6 month period during study
• No concurrent hormonal or steroidal therapy, including topical corticosteroids
• Concurrent hormone replacement therapy (e.g., estrogen or thyroid hormone replacement) allowed

Radiotherapy:

• At least 6 months since prior local radiotherapy to areas being studied
• At least 30 days since other prior radiotherapy
• No concurrent radiotherapy, including local radiotherapy to areas being studied

Surgery:

• Not specified

Other:

• At least 30 days since prior cryotherapy to target lesions
• At least 60 days since prior laser resurfacing, dermabrasion, or chemical peels
• At least 30 days since prior investigational medication
• At least 14 days since prior topical alphahydroxyacids (e.g., glycolic acid or lactic acid) or retinoids
• At least 30 days since prior systemic psoralens or retinoids
• At least 30 days since prior treatment for esophageal, gastric, pyloric channel, or duodenal ulcers
• At least 30 days since prior aspirin (more than 100 mg/day), other nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors at a frequency of at least 3 times per week for more than 2 weeks (except cardioprotective doses of aspirin (no more than 100 mg/day)
• No concurrent systemic psoralens or retinoids
• No concurrent prescription or over-the-counter topical medications to areas being studied (e.g., vitamin A derivatives)
• No concurrent cryotherapy to target lesions
• No concurrent laser resurfacing, dermabrasion, or chemical peels
• No other concurrent investigational medications
• No concurrent fluconazole or lithium
• No concurrent chronic NSAIDs or COX-2 inhibitors (at least 3 times per week for more than 2 consecutive weeks per year)
• Concurrent cardioprotective doses of oral aspirin (100 mg per day or less) allowed
• Concurrent moisturizer/emollient or sunscreen allowed