Thompson, SL

9116 Background: Hot flashes affect 75 % to 90 % of women transitioning to menopause and are a major cause of morbidity among breast cancer survivors. Levetiracetam, a popular anticonvulsant, is a centrally active agent that anecdotally appeared to reduce hot flashes in clinical practice. This phase II trial sought to evaluate the efficacy of levetiracetam in reducing hot flashes among women with a history of breast cancer or women who did not wish to take estrogen therapy for fear of an increased risk of breast cancer. Methods: Women who were experiencing bothersome hot flashes (≥ 14 times per week, for ≥ 1 month) were eligible. A single arm pilot study design based on previous work was used with a planned sample size of 30 patients. The patients did not receive any study medication during the first week (baseline week). At the beginning of the second week, patients were started on levetiracetam (500 mg), and were to increase the dose by 500 mg each week to a goal of 1,000 mg twice daily. Hot flash diaries were completed daily. The primary endpoint was hot flash score (frequency times average severity). The change from week 1 (baseline) to week 5, the last treatment week, was analyzed by paired t-test and related Wilcoxon procedures. Results: A total of 30 women were enrolled onto this study in eight months. All patients were eligible. 19 women completed all 4 weeks of the study treatment and provided complete data. After treatment with levetiracetam for 4 weeks, mean hot flash scores were reduced by 57% (95% CI 39%-75%), while mean hot flash frequencies were reduced by 53% (95% CI 38%-68%), reductions being greater than what would be expected with a placebo. There were significant improvements, compared to baseline week data, in sweating, hot flash distress, and satisfaction with hot flash control. Eight subjects stopped the study drug due to treatment related adverse events (grade I/II), with the most frequently reported being somnolence, fatigue and dizziness. Conclusions: While levetiracetam appears to be a promising therapy for the treatment of hot flashes, further study is needed to better substantiate the toxicity and efficacy of this drug before it can be more definitively recommended for use in clinical practice. No significant financial relationships to disclose.

Abstract Background: It has long been known that chemotherapy can result in premature menopause, causing follicular senescence and estrogen depletion with associated hot flashes and mood alterations. What is less well appreciated is whether the stroma of the ovary is equally impacted after chemotherapy, resulting in androgen deprivation. The aim of this pilot study was to evaluate whether androgen levels are adversely affected after chemotherapy and whether this is associated with unwanted symptoms. Methods: Women who were premenopausal, newly diagnosed with breast cancer, and about to undergo adjuvant chemotherapy were followed longitudinally. Women with adrenal insufficiencies, taking steroids, oral contraceptives, or had had previous chemotherapy were excluded. Self report questionnaires regarding sexual function, fatigue, mood, menstrual symptoms; menstrual diaries; and blood were collected at 4 points: before treatment, mid chemotherapy, post chemotherapy and 6 months later. Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) (adrenal hormone), bioavailable testosterone (bioT), androstenedione (Adione) (stromal hormone), estrone (E1), estradiol (E2) (follicular hormone), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH) were evaluated. Descriptive statistics, comparisons of means by two sided t-tests and Pearson correlation coefficients were computed. Six month post treatment data are reported. Results: 24 women were accrued and 21 provided serum and questionnaires through 6 months. All sex steroid hormones decreased during chemotherapy and did not return to baseline by 6 months for the group as a whole. At 6 months, 14 women were postmenopausal per FSH, E2 and menstrual diaries and 7 had resumed menses. There were no significant differences in hormone concentrations at baseline between women who ended up menopausal from those who resumed menses. However, at 6 months, postmenopausal women had significantly lower concentrations than premenopausal women of E2 (289 pg/ml pre- 9 pg/ml post), E1 (132 pg/ml pre- 22 pg/ml post), and Adione (102 ng/dL pre- 56 ng/dL post), but not DHEA-S or bioT (all p < .01). E2 was significantly correlated with Adione (R = .47 p = .03), and E1 (R = .57, p = .007). Low to moderate correlations were found between hormone concentrations and symptoms. The use of tamoxifen was significantly, and negatively correlated with the total score on the Female Sexual Function Index (r = −.572, p = .005), indicating worse sexual function for women on tamoxifen. Conclusion: These data support the hypothesis that the post chemotherapy ovary suffers both follicular and stromal dysfunction, as noted by lower Adione, which is specific to the ovarian stroma. Adione concentrations in the postmenopausal group women are similar to published reports of women post oophorectomy. This is the first longitudinal study we are aware of to evaluate ovarian stromal function in women undergoing chemotherapy. This total hormone depletion may be why women experiencing chemotherapy induced menopause report severe and distressing menopausal symptoms such as hot flashes. Estrogen is often implicated, but androgen deprivation in this population should be taken into consideration when planning interventions to improve health related quality of life. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-01.