Medroxyprogesterone Compared With Venlafaxine in Treating Hot Flashes in Women

Phase III Comparison of Depomedroxyprogesterone Acetate (DPROV) to Venlafaxine for Managing Hot Flashes

RATIONALE: Medroxyprogesterone and venlafaxine may be effective in relieving hot flashes. It is not yet known whether venlafaxine is more effective than medroxyprogesterone in relieving hot flashes.

PURPOSE: Randomized phase III trial to compare the effectiveness of medroxyprogesterone with that of venlafaxine in treating women who are experiencing hot flashes.

OBJECTIVES:

• Compare the efficacy of medroxyprogesterone administered as 1 injection vs medroxyprogesterone administered as 3 injections (closed to accrual as of 1/22/03) vs venlafaxine for hot flash alleviation in women with symptomatic hot flashes.
• Compare the toxic effects of these regimens in these patients.
• Determine whether there is cross resistance between these 2 drugs in these patients.
• Compare the 1-year efficacy of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to age (18 to 49 vs 50 and over), current tamoxifen use (yes vs no), current raloxifene use (yes vs no), duration of hot flash symptoms (less than 9 months vs 9 months or more), and average frequency of hot flashes per day (2-3 vs 4-9 vs 10 or more). Patients are randomized to 1 of 2 treatment arms. (Arm II closed to accrual as of 1/22/03.)

All patients complete a daily questionnaire regarding number of hot flashes beginning on day 1 and continuing for 7 weeks. Patients are randomized to one of three treatment arms.

DISEASE CHARACTERISTICS:

• History of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ (currently without evidence of malignant disease) OR
• Concerns about taking estrogen for fear of breast cancer
• Bothersome hot flashes, defined as occurrence at least 14 times per week and of sufficient severity as to make patient desire therapeutic intervention
• Presence of hot flashes for at least 1 month
• Hormone receptor status:

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Performance status:

• ECOG 0-1

Life expectancy:

• At least 6 months

Cardiovascular:

• No prior thromboembolic disease
• No uncontrolled hypertension (persistent diastolic blood pressure greater than 95 mm Hg and/or systolic blood pressure greater than 160 mm Hg)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Chemotherapy:

• More than 4 weeks since prior antineoplastic chemotherapy
• No concurrent antineoplastic chemotherapy unless clinically appropriate

Endocrine therapy:

• More than 4 weeks since prior androgen or estrogen therapy
• More than 3 months since prior progesterone as part of hormone replacement therapy
• At least 1 year since any other progesterone therapy (including megestrol)
• No concurrent androgen, estrogen, or progestational agents unless clinically appropriate
• Concurrent tamoxifen, raloxifene, or aromatase inhibitors are allowed if started more than 4 weeks ago and continuation for more than 5 weeks is planned

Other:

• More than 2 weeks since prior agents for treatment of hot flashes (e.g., clonidine, Bellergal-S, or vitamin E of more than 400 mg per day)
• More than 1 year since prior antidepressants (including Hypericum perforatum [St John's Wort])
• No other concurrent antidepressants or monoamine oxidase inhibitors
• No other concurrent agents for treatment of hot flashes (e.g. clonidine, Bellergal-S, or vitamin E of more than 400 mg per day)