Diindolylmethane in Treating Patients With Abnormal Cervical Cells
Diindolylmethane in Treating Patients With Abnormal Cervical Cells
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use
 of diindolylmethane, a substance found in cruciferous vegetables, may keep cervical
 intraepithelial neoplasia or cervical cancer from forming.

 PURPOSE: This randomized phase III trial is studying diindolylmethane to see how well it
 works compared to a placebo in treating patients with abnormal cervical cells.
OBJECTIVES:

 -  Compare the effect of diindolylmethane vs placebo in reducing the prevalence of
 histologically proven high-grade cervical intraepithelial neoplasia in patients with
 low-grade cervical cytological abnormalities.

 -  Compare the effect of these regimens in reducing the prevalence of cytological
 abnormalities in these patients.

 -  Compare the effect of these regimens in changing the clinical appearance of the cervix
 in these patients.

 -  Determine if diindolylmethane offers benefits in relation to human papillomavirus (HPV)
 status, including HPV type, viral load, and integration.

 -  Determine the side effects of supplementation with diindolylmethane.

 -  Determine the effects of this drug on migraine, mastalgia, weight, and premenstrual
 syndrome (PMS).

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

 -  Arm I: Patients receive oral diindolylmethane once daily for 6 months.

 -  Arm II: Patients receive oral placebo once daily for 6 months. Patients undergo cervical
 sampling at baseline and at 6 months for Pap testing by liquid based cytology and human
 papillomavirus (HPV) testing by polymerase chain reaction. Some patients also undergo
 urine and hair sample collection at baseline and at 3 and 6 months. Samples are analyzed
 for estrogen and diindolylmethane metabolites, to monitor patient compliance and
 response to treatment. Some patients have a cervical photograph taken using a colposcope
 at baseline and at 6 months. All patients undergo colposcopy at 6 months.

 Patients complete a questionnaire at baseline (i.e., for reproductive history, diet, smoking,
 and premenstrual symptoms) and at 6 months (i.e., for side effects, compliance, changes in
 smoking, and contraception use). Patients with moderate to severe premenstrual syndrome (PMS)
 also complete PMS questionnaires once monthly during months 1-6 and 4 months following
 completion of study therapy. All patients are instructed to maintain current diet and to keep
 cruciferous vegetables and soy products constant during study course.

 After completion of study treatment, patients are followed periodically for up to 7 years.

 PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study.
DISEASE CHARACTERISTICS:

 -  First mildly dyskaryotic Pap smear or a second borderline Pap smear taken within the
 Cervical Screening Wales program

 -  Patients under surveillance following treatment for high-grade cervical
 intraepithelial neoplasia are not eligible

 -  No clinical suspicion of a concurrent invasive cervical cancer

 PATIENT CHARACTERISTICS:

 -  No invasive cancer within the past 3 years

 -  No known HIV positivity

 -  Not pregnant or nursing

 -  Not planning to become pregnant within the next 6 months

 PRIOR CONCURRENT THERAPY:

 -  No concurrent immunosuppressive drugs, warfarin, or theophylline

 -  No concurrent proton pump inhibitor drugs for ulcer or reflux disease (i.e.,
 rabeprazole, esomeprazole magnesium, lansoprazole, omeprazole, or pantoprazole sodium)