Pregabalin in Treating Women With Hot Flashes

OBJECTIVES:

- To evaluate the efficacy of 150 mg of pregabalin versus placebo on hot flash scores in
women with a history of breast cancer or women who do not wish to take estrogen therapy
for fear of increased risk of breast cancer.

- To evaluate the side effect profile of different doses of pregabalin in these patients.

- To evaluate the effect of 150 mg of pregabalin versus placebo on the secondary outcome
of interference of activities from hot flashes in these patients.

- To evaluate the efficacy and side effect profile of 75 mg of pregabalin versus placebo
in these patients.

OUTLINE: Patients are stratified according to age (18-49 years vs ≥ 50 years); selective
estrogen-receptor modulator (i.e., tamoxifen or raloxifene) or aromatase inhibitor use (yes
vs no); duration of hot flashes (< 9 months vs ≥ 9 months); and frequency of hot flashes per
24-hour period (4-9 vs ≥ 10). Patients are randomized to 1 of 3 treatment arms.

- Arm I: Patients receive 75 mg of oral pregabalin twice daily for 6 weeks.

- Arm II: Patients receive 150 mg of oral pregabalin twice daily for 6 weeks.

- Arm III: Patients receive oral placebo twice daily for 6 weeks. Treatment in all arms
continues in the absence of unacceptable toxicity.

Patients complete Hot Flash Diaries at baseline and once daily during treatment and the
Symptom Experience Diary at baseline and once weekly during treatment. Patients also
complete the Profile of Mood States and the Hot Flash Related Daily Interference Scale
questionnaires at baseline and after completion of study treatment.

DISEASE CHARACTERISTICS:

- Meeting 1 of the following criteria:

- History of breast cancer (currently without malignant disease)

- No history of breast cancer, but patient wishes to avoid estrogen due to a
perceived increased risk of breast cancer

- Bothersome hot flashes (defined by their occurrence ≥ 28 times per week and of
sufficient severity to make the patient desire therapeutic intervention)

- Presence of hot flashes for ≥ 1 month prior to study entry

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Life expectancy ≥ 6 months

- Able to complete questionnaire(s) by themselves or with assistance

- Women of childbearing potential not eligible (per the judgment of the attending
clinician)

- Serum creatinine ≤ 1.5 times upper limit of normal

PRIOR CONCURRENT THERAPY:

- No prior gabapentin or pregabalin

- More than 4 weeks since prior and no concurrent antineoplastic chemotherapy,
androgens, estrogens, or progestational agents

- Vaginal estrogen is allowed if used for the past month and not planned to be
discontinued

- Concurrent adjuvant targeted therapy (i.e., lapatinib, trastuzumab [Herceptin®])
allowed in patients with no evidence of disease

- Concurrent tamoxifen, raloxifene, or aromatase inhibitors on a constant dose for at
least 4 weeks allowed provided the medication will not be stopped during the study
period

- No concurrent or planned use of other agents for hot flashes except for any of the
following:

- Stable dose of vitamin E is allowed as long as agent was started > 30 days prior
to study initiation and is to be continued throughout the study period

- Soy is allowed, if it is planned to be continued at the same dose during the
study period

- Stable dose of antidepressants is allowed as long as it was started > 30 days
prior to study initiation and is to be continued at a stable dose throughout the
study period