S9626: Megestrol in Treating Hot Flashes Following Treatment for Breast Cancer

• Document any effects of various dose levels of megestrol acetate on atrophic vaginitis and dyspareunia [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: No ]
• Evaluate toxicity of two dose levels of megestrol acetate relative to placebo [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: Yes ]
• Feasibility of accrual patients to placebo-controlled study [ Time Frame: At registration ] [ Designated as safety issue: No ]

RATIONALE: Megestrol may be effective in treating hot flashes following treatment for breast cancer. It is not yet known which regimen of megestrol is most effective for hot flashes.

PURPOSE: Randomized phase III trial to compare the effectiveness of different doses of megestrol in treating hot flashes in patients who have undergone therapy for breast cancer.

OBJECTIVES: I. Compare the effectiveness and duration of the benefit of placebo versus low dose megestrol versus high dose megestrol in the reduction of severe and/or frequent hot flashes in patients with previously treated invasive breast cancer. II. Document the effects of various dose levels of megestrol on atrophic vaginitis and dyspareunia in these patients. III. Evaluate the toxicity of this treatment in these patients.

OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are stratified according to tamoxifen use (yes vs no), number of hot flashes per week (5-34 vs 35-63 vs more than 63), and duration of hot flashes (6 months or less vs longer than 6 months). Patients are randomized to one of three treatment arms. Arm I: Patients receive oral placebo daily. Arm II: Patients receive lower dose oral megestrol daily. Arm III: Patients receive higher dose oral megestrol daily. Patients who do not respond after 3 months of treatment receive an additional dose of oral megestrol daily. Treatment continues for a total of 6 months in the absence of disease progression or unacceptable toxicity. Patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 279 eligible patients (93 per arm) are expected to be accrued.

• Breast Cancer
• Hot Flashes

• Active Comparator: Megestrol Acetate 20 mg/day
  Double blinded study drug taken for 3 months
  Intervention: Drug: megestrol acetate
• Active Comparator: Megestrol Acetate 40 mg/day
  Double blinded drug taken for 3 months
  Intervention: Drug: megestrol acetate
• Placebo Comparator: Placebo
  Double blinded drug taken for 3 months

DISEASE CHARACTERISTICS: Diagnosis of infiltrating breast cancer (T1-3, N0-1, M0) treated with appropriate local and regional therapy Chemotherapy and/or surgery completed At least 10 hot flashes per week OR At least 5 severe or very severe hot flashes per week No prior participation in NCI sponsored breast cancer adjuvant protocol No recurrent or persistent vaginal bleeding If postmenopausal and had any vaginal bleeding within past year, then must have normal endometrial biopsy Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: Not specified Menopausal status: Pre or postmenopausal Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Cardiovascular: No history of deep vein thrombosis Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior malignancy in past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other adequately treated stage I or II cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No concurrent chemotherapy Endocrine therapy: Prior hormonal therapy allowed At least 6 months since prior megestrol At least 1 week since prior nonestrogen containing steroid hormones (except tamoxifen) Concurrent tamoxifen allowed only if begun at least 4 months prior to study No other concurrent nonestrogen containing steroid hormones No concurrent estrogen or hormone replacement therapy Radiotherapy: Concurrent radiotherapy allowed Surgery: See Disease Characteristics Prior hysterectomy allowed No concurrent surgery Other: Concurrent nonhormonal prescription or nonprescription medications for hot flashes allowed (e.g., clonidine, ergotamine tartrate, vitamin E, or soy)