A Phase III Randomized Trial of Topical Vaginal Fluorouracil (5-Fluorouracil, 5-FU) Maintenance Therapy Versus Observation After Standard Treatment for High-Grade Cervical Dysplasia in HIV-Infected Women

A Phase III Randomized Trial of Topical Vaginal Fluorouracil (5-Fluorouracil, 5-FU) Maintenance Therapy Versus Observation After Standard Treatment for High-Grade Cervical Dysplasia in HIV-Infected Women

To determine the efficacy and safety of intravaginal fluorouracil administered as prophylaxis in HIV-infected women who have received standard ablative therapy (surgery) for high-grade cervical dysplasia (pre-cancer of the cervix; cervical intraepithelial neoplasia). To correlate time to recurrence of cervical dysplasia with T-cell function.

Women with HIV infection are at greater risk for cervical dysplasia. Because of the likelihood that untreated or recurrent cervical dysplasia may progress to invasive cancer, there is an urgent need to develop appropriate therapies.

Women with HIV infection are at greater risk for cervical dysplasia. Because of the likelihood that untreated or recurrent cervical dysplasia may progress to invasive cancer, there is an urgent need to develop appropriate therapies.

Patients are randomized to receive either intravaginal fluorouracil or no treatment (observation only). Fluorouracil cream is self-administered via applicator at biweekly intervals for 6 months. Patients are evaluated for recurrent cervical dysplasia by cytology and colposcopy with or without biopsy.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiretrovirals (AZT, ddI, ddC) and immunomodulators (interferon and interleukin).
• Prophylaxis or treatment for opportunistic infections.
• Vaginal antifungal agents or other indicated vaginal medications (although not permitted on day of fluorouracil application).
• Contraceptives.
• Acyclovir (prophylaxis or treatment) in patients with a history of primary or recurrent genital herpes.

Patients must have:

• HIV infection.
• Prior cervical dysplasia (grade II or III cervical intraepithelial neoplasia) successfully treated with an ablative procedure within the past 12 weeks.
• Patients less than 18 years of age must have consent of parent or guardian.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Untreated or persistent vaginal or vulvar dysplasia.
• Colposcopy or biopsy inconclusive or positive for dysplasia.
• Active genital ulcerative disease such as syphilitic chancre or herpes ulcer.
• Adenocarcinoma in situ.

Concurrent Medication:

Excluded:

• Cytotoxic chemotherapy for malignancy.
• High-dose steroids (> 10 mg/day prednisone or its steroid equivalent).

Patients with the following prior conditions are excluded:

• Malignancy requiring cytotoxic chemotherapy within the 3 months prior to study entry.
• Prior hysterectomy.
• History of allergic reaction or severe hypersensitivity to fluorouracil.

Prior Medication:

Excluded:

• Fluorouracil (systemic or topical) within 3 months prior to study entry.