Loprinzi, C.L., Sloan, J.A., Perez, E.A., Quella, S.K., Stella, P.J., Mailliard, J.A., … Rummans, T.A. (2002). Phase III evaluation of fluoxetine for treatment of hot flashes. Journal of Clinical Oncology, 20, 1578–1583.

The study sought to assess the efficacy of fluoxetine for treatment of hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen because of a breast cancer risk.

Patients received four weeks of fluoxetine (20 mg/day orally) versus an identical-appearing placebo. For the next four weeks, patients were crossed over to the alternative arm.

The study enrolled 81 women with a history of breast cancer or a perceived increased risk of breast cancer. Sevent-two patients completed the study. Their mean age was older than 50 years.

• Inclusion criteria:
  • Women with a history of breast cancer or a perceived increased risk of breast cancer 
  • Patients without current evidence of malignant disease 
  • History of bothersome hot flashes (at least 14 per week) that were severe enough for patients to desire intervention; hot flashes present for at least one month
  • Concomitant therapy with tamoxifen or raloxifene was permitted if patient wason  therapy for at least one month and was planning continuation of therapy during study.
• Exclusion criteria:
  • Concomitant therapy with antineoplastic chemotherapy, androgens, estrogens, progestational drugs, or warfarin use
  • Previous use of fluoxetine antidepressant use for two years prior to study entry

This was a placebo-controlled, double-blind, cross-over clinical trial.

Assessments included:

• Daily hot flash diary for nine weeks
• Toxicity questionnaire weekly
• Beck Depression Inventory
• Uniscale global QOL instrument at study entry and study completion

At the end of the first treatment period (four weeks), hot flash scores (frequency x average severity) decreased 50% inthe  fluoxetine arm versus 36% in the placebo arm. Cross-over analysis showed a significantly greater improvement in hot flash scores with fluoxetine than placebo (p = .02). More than half (54%) of the patients reported depressive symptoms of at least mild severity at baseline compared with only 30% of patients after the first treatment period and 21% after the second treatment period. After five weeks of treatment, QOL did not differ between groups. After cross-over, QOL showed a relative improvement trend for fluoxetine compared to placebo.

Age and tamoxifen use were not adjusted for as potential confounding factors.