Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7

Missouri Valley Cancer Consortium, Omaha, Nebraska, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 04/2006; 24(9):1409-14. DOI: 10.1200/JCO.2005.04.7324
Source: PubMed


Vasomotor hot flashes are a common problem in menopausal women. Given concerns regarding estrogen and/or combined hormonal therapy, other treatment options are desired. Prior trials have confirmed that progestational agents and newer antidepressants effectively reduce hot flashes. This current trial compared a single intramuscular dose of medroxyprogesterone acetate (MPA), depot preparation, versus daily oral venlafaxine as treatment for hot flashes.
Women with bothersome hot flashes were entered onto this trial, were randomly assigned to treatment, and then had a baseline week where hot flash scores were recorded without treatment. They were then treated and observed for 6 weeks; daily diaries were used to measure hot flash frequencies and severities. There were 109 patients per each arm randomly assigned to receive MPA 400 mg intramuscularly for a single dose versus venlafaxine 37.5 mg per day for a week, then 75 mg per day.
During the sixth week after random assignment, hot flash scores were reduced by 55% in the venlafaxine arm versus 79% in the MPA arm (P < .0001). In an intention-to-treat analysis, 46% of venlafaxine patients (50 of 109) compared with 74% of the MPA patients (81 of 109) had a decrease in hot flashes by more than 50% from baseline (P < .0001). Less toxicity was reported in the MPA arm.
A single MPA dose seems to be well tolerated and more effectively reduces hot flashes than does venlafaxine.

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    • "In conclusion, though some studies dispute venlafaxine's efficacy (Evans et al. 2005; Vitolins et al. 2013) several other studies suggest a beneficial effect of venlafaxine in the treatment of post-menopausal vasomotor symptoms, also for breast and prostate cancer survivors, either alone (Loprinzi et al. 1998; Carpenter et al. 2007; Quella et al. 1999), or against placebo (Loprinzi et al. 2000), or compared to another active compound (Loprinzi et al. 2006; Loibl et al. 2007; Buijs et al. 2009; Boekhout et al. 2011; Bordeleau et al. 2010). However, the treatment duration of each of these studies was too short to investigate a potential increase in breast cancer recurrence. "
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    ABSTRACT: The cardinal climacteric symptoms of hot flushes and night sweats affect 24-93% of all women during the physiological transition from reproductive to post-reproductive life. Though efficacious, hormonal therapy and partial oestrogenic compounds are linked to a significant increase in breast cancer. Non-hormonal treatments are thus greatly appreciated. This systematic review of published hormonal and non-hormonal treatments for climacteric, and breast and prostate cancer-associated hot flushes, examines clinical efficacy and therapy-related cancer risk modulation. A PubMed search included literature up to June 19, 2014 without limits for initial dates or language, with the search terms, (hot flush* OR hot flash*) AND (clinical trial* OR clinical stud*) AND (randomi* OR observational) NOT review). Retrieved references identified further papers. The focus was on hot flushes; other symptoms (night sweats, irritability, etc.) were not specifically screened. Included were some 610 clinical studies where a measured effect of the intervention, intensity and severity were documented, and where patients received treatment of pharmaceutical quality. Only 147 of these references described studies with alternative non-hormonal treatments in post-menopausal women and in breast and prostate cancer survivors; these results are presented in Additional file 1. The most effective hot flush treatment is oestrogenic hormones, or a combination of oestrogen and progestins, though benefits are partially outweighed by a significantly increased risk for breast cancer development. This review illustrates that certain non-hormonal treatments, including selective serotonin reuptake inhibitors, gabapentin/pregabalin, and Cimicifuga racemosa extracts, show a positive risk-benefit ratio. Key pointsSeveral non-hormonal alternatives to hormonal therapy have been established and registered for the treatment of vasomotor climacteric symptoms in peri- and post-menopausal women.There are indications that non-hormonal treatments are useful alternatives in patients with a history of breast and prostate cancer. However, confirmation by larger clinical trials is required.
    SpringerPlus 12/2015; 4(1). DOI:10.1186/s40064-015-0808-y
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    • "At the end of 8 weeks, the women showed a significant improvement in the Montgomery–Asberg Depression Rating Scale score from baseline (P < 0.001).58 Trials evaluating the SNRI venlafaxine for VMS have yielded positive results, showing an approximate 55% reduction in VMS.59,60 In one study, 191 postmenopausal women were assigned to placebo or to target venlafaxine doses of 37.5 mg/day, 75 mg/day, or 150 mg/day. "
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    ABSTRACT: Vasomotor symptoms (VMS), including hot flashes and night sweats, occur in as many as 68.5% of women as a result of menopause. While the median duration of these symptoms is 4 years, approximately 10% of women continue to experience VMS as many as 12 years after their final menstrual period. As such, VMS have a significant impact on the quality of life and overall physical health of women experiencing VMS, leading to their pursuance of treatment to alleviate these symptoms. Management of VMS includes lifestyle modifications, some herbal and vitamin supplements, hormonal therapies including estrogen and tibolone, and nonhormonal therapies including clonidine, gabapentin, and some of the serotonin and serotonin-norepinephrine reuptake inhibitors. The latter agents, including desvenlafaxine, have been the focus of increased research as more is discovered about the roles of serotonin and norepinephrine in the thermoregulatory control system. This review will include an overview of VMS as they relate to menopause. It will discuss the risk factors for VMS as well as the proposed pathophysiology behind their occurrence. The variety of treatment options for VMS will be discussed. Focus will be given to the role of desvenlafaxine as a treatment option for VMS management.
    International Journal of Women's Health 07/2012; 4(1):305-19. DOI:10.2147/IJWH.S24614
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    • "Based on the evidence, venlafaxine and desvenlafaxine are both viable options for reducing the frequency and severity of hot flashes. Venlafaxine has been shown to reduce hot flashes by 37 to 61 percent4,1617 and desvenlafaxine by 55 to 69 percent.18,19,20 Similar to most other trials assessing treatment for vasomotor symptoms, the placebo rates were elevated in these studies (15-51%). "
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    ABSTRACT: Vasomotor flushes are common complaints of women during and after menopause, affecting about 75 percent of this population. Estrogen therapy is the most effective treatment for hot flashes. However, there are a significant number of women who have contraindications or choose not to use estrogen due to potential risks such as breast cancer and thromboembolic disorders. These women need alternative options. The selective norepinephrine reuptake inhibitors, venlafaxine and desvenlafaxine, have shown efficacy in alleviating hot flashes. The purpose of this review is to assess the efficacy and tolerability of these two agents for treatment of hot flashes in healthy postmenopausal women. A literature search of the MEDLINE and Ovid databases from inception to June 2011 was conducted. Randomized controlled trials, published in English, with human participants were included. Studies included postmenopausal women, and trials with breast cancer only populations were excluded. Venlafaxine reduced hot flashes by 37 to 61 percent and desvenlafaxine by 55 to 69 percent. Both agents were well tolerated. The most common adverse effects were headache, dry mouth, nausea, insomnia, somnolence, and dizziness. Based on the evidence, venlafaxine and desvenlafaxine are both viable options for reducing the frequency and severity of hot flashes.
    07/2011; 9(3):117-21.
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