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.
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.
San Juan City Hosp, San Juan 009367344, Puerto Rico
Univ of Puerto Rico, San Juan 009365067, Puerto Rico
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl, Chicago, Illinois 60611, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Univ of Chicago Children's Hosp, Chicago, Illinois 606371470, United States
Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Children's Hosp of Michigan, Detroit, Michigan 48201, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States
St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr, New York, New York 10021, United States
King's County Hosp Ctr / Pediatrics, Brooklyn, New York 11203, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States
Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States
SUNY / Health Sciences Ctr at Brooklyn, Brooklyn, New York 112032098, United States
Saint Clare's Hosp and Health Ctr, New York, New York 10019, United States
Adirondack Med Ctr at Saranac Lake, Albany, New York 122083479, United States
Mid - Hudson Care Ctr, Albany, New York 122083479, United States
Albany Med College / Division of HIV Medicine A158, Albany, New York 122083479, United States
Harlem Hosp Ctr, New York, New York 10037, United States
Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States
Univ of Washington, Seattle, Washington 981224304, United States
Robinson WR, Morris CB. Cervical neoplasia. Pathogenesis, diagnosis, and management. Hematol Oncol Clin North Am. 1996 Oct;10(5):1163-76. Review.
Maiman M, Watts DH, Andersen J. A phase three randomized trial of topical vaginal 5-fluorouracil maintenance therapy versus observation after standard treatment for high grade cervical dysplasia in HIV-infected women: ACTG 200. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:155 (abstract no 466)
