Management Of Hot Flashes Research Articles

Abstract ES4-1: Navigating the Obstacles and Risks of Survivorship: Breast Cancer Sexuality: Issues and Answers

Abstract The sexual consequences of breast cancer and its treatments are well known. Sexual difficulties include alteration in hormonal levels, changes in sexual organs and anatomy, vaginal and vulvar dryness, changes in libido, increased latency to orgasm and decreased intensity of orgasmic response. Changes in body image, sexual self-esteem and relationship dynamic tension may present as survivorship challenges for the breast cancer patient and her partner. Severe vulvo vaginal and clitoral atrophy as a result of chemotherapy and/or adjuvant hormone therapy, and loss of libido secondary to dyspareunia are widespread. Cytostatic medications that are prescribed for long-term use (aromatase inhibitors) can impact bone health, sexual functioning/satisfaction and overall quality of life. Many women on aromatase inhibitors have severe complaints of vulvar and vaginal atrophy. Sexual dysfunction is common for breast cancer population and limited acceptable treatments are available. Minimally absorbed local vaginal estrogen use in this population remains controversial and a hotly debated controversial topic. More data should be forthcoming. There are multiple new innovative treatments in the research pipeline for female sexual dysfunction. DHEA intravaginal suppositories, Flibanserin and Bremelanotide (PT 141) remain promising although they have not been adequately studied in the breast cancer population. Ospemifene a novel estrogen agonist/ antagonist has demonstrated a strong estrogenic effect on the vaginal epithelium during a three month trial period and did not stimulate the endometrium; however, the medication did mildly aggravate hot flashes (this did not lead to drug discontinuation). Although not studied in breast cancer patients, pivotal Phase 3 data confirmed effectiveness of ospemifene as effective treatment for vulvovaginal atrophy. In a recent article in Menopause, Ospemifene and 4-hydroxyospemifene effectively prevented and treat breast cancer in Mtag. TG Transgenic Mouse. Testosterone use remains off label and is not FDA approved, yet it is widely used in the non cancer population. New emerging safety data will be presented. Vaginal moisturizers, lubricants and dilators in association with genito pelvic floor therapy and intravaginal valium suppositories can be considered front line treatment for atrophy, dyspareunia and hypertonic vaginismus. New innovative data on non hormonal management of hot flashes is and important initial step in the overall management of the breast cancer patient who is suffering from sexual dysfunction. A multi model treatment paradigm will be presented which will include pharmacologic, nonpharmacologic, and psychosocial interventions. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES4-1.

Method Development and Validation for Ultra-High-Pressure LC/MS/MS Determination of Hop Prenylflavonoids in Human Serum

Hops (Humulus lupulus L.) are used in the brewing of beer, and hop extracts containing prenylated compounds, such as xanthohumol (XN) and 8-prenylnaringenin (8-PN), are under investigation as dietary supplements for cancer chemoprevention and the management of hot flashes in menopausal women. To facilitate clinical studies of hop safety and efficacy, a selective, sensitive, and fast ultra-high-pressure LC (UHPLC) tandem MS method was developed and validated for the simultaneous determination of the hop prenylflavonoids XN, isoxanthohumol (IX), 6-prenylnaringenin (6-PN), and 8-PN in human serum. The analytical method requires 300 microL of human serum, which is processed using liquid-liquid extraction. UHPLC separation was carried out in 2.5 min with gradient elution using an RP C18 column containing 1.6 pm particle size packing material. Prenylflavonoids were measured using negative ion electrospray MS with collision-induced dissociation and selected reaction monitoring. The method was validated and showed good accuracy and precision with an LOQ of 0.50 ng/mL for XN (1.4 nM) and 1.0 ng/mL for 6-PN, 8-PN (2.94 nM), and IX (2.82 nM) in serum.

Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up

We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8). In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.

Acupuncture for Hot Flashes: Decision Making by Breast Cancer Survivors

Hot flashes (HFs) are a particularly common and distressing symptom among breast cancer survivors (BCSs). Given its low rate of side effects, acupuncture shows promise as a therapeutic approach for HFs, but little is known about BCS's decision making about the use of acupuncture. This study seeks to identify attitudes and beliefs about using acupuncture for HFs by BCSs. Using the Theory of Planned Behavior (TPB) as a conceptual framework, we conducted semistructured interviews among women with stage I-III breast cancer who had finished primary treatment and were currently experiencing HFs. Interviews were taped, transcribed, and coded. We used a modified grounded theory approach to analyze the data. Twenty-five BCSs (13 whites/12 African American) participated in the study. Respondents stated that their intended use of acupuncture for HFs would be dependent on (1) expected therapeutic effects (eg, pain relief, energy); (2) practical concerns (eg, fear of needles, practitioner experience, time commitment); and (3) source of decision support/validation (eg, family members, physicians, self). Although constructs in the TPB accounted for many decision factors, respondents identified 2 major themes outside of the TPB: (1) viewing acupuncture as a natural alternative to medications, and (2) assessing the degree of HFs as bothersome enough in the context of other medical comorbidities to trigger the need for therapy. BCSs expressed varied expected therapeutic benefits, practical concerns, and decision support, emphasizing the "natural appeal" and symptom appraisal as key determinants when using acupuncture for HFs. Incorporating these factors in counseling BCSs may promote patient-centered communication, leading to improved hot flash management and quality of life.

Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial

Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial

Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial

Management of hot flashes in patients who have breast cancer with venlafaxine and clonidine: a randomized, double-blind, placebo-controlled trial

Hot Flashes: A Review of Pathophysiology and Treatment Modalities

Many therapies are being studied for the treatment of hot flashes for individuals with cancer, yet few studies have demonstrated safe and effective clinical benefit for those who suffer from this distressing symptom. The purpose of this paper is to assess the current options for the management of hot flashes, examining key endpoints from recent clinical trials and reviewing future directions. Hot flashes are a common stressful symptom for individuals with cancer, particularly women with a history of breast cancer and men with prostate cancer. Lifestyle modifications are proposed as the first step in the management of less severe hot flashes. Several publications have addressed nonhormonal agents as a treatment option for hot flashes. Newer antidepressant and anticonvulsant agents have been studied and show potential in treating vasomotor symptoms. Although many complementary and alternative therapies, including herbal medications and phytoestrogens, have been studied for the treatment of hot flashes, none are clinically recommended at this time. Additionally, further evidence is needed for supportive exercise such as yoga and relaxation techniques. Acupuncture may warrant further investigation in the reduction and severity of hot flashes in both men and women. Hormonal therapies, including estrogens and progestogens, are the most well-known and efficient agents in alleviating hot flashes; however, the safety of these agents is disputable.

Nonestrogenic Management of Hot Flashes

Nonestrogenic Management of Hot Flashes

Management of Hot Flashes in Patients Who Have Breast Cancer With Venlafaxine and Clonidine: A Randomized, Double-Blind, Placebo-Controlled Trial

Therapies for breast cancer may induce hot flashes that can affect quality of life. We undertook a double-blind, placebo-controlled trial with the primary objective of comparing the average daily hot flash scores in the twelfth week among patients treated with venlafaxine, clonidine, and placebo. Additional analyses of the hot flash score over the full 12 weeks of treatment were performed. In all, 102 patients with a history of breast cancer were randomly assigned (2:2:1) to venlafaxine 75 mg, clonidine 0.1 mg, or placebo daily for 12 weeks. Questionnaires at baseline and during treatment assessed daily hot flash scores, sexual function, sleep quality, anxiety, and depression. After 12 weeks, a total of 80 patients were evaluable for the primary end point. During week 12, hot flash scores were significantly lower in the clonidine group versus placebo (P = .03); for venlafaxine versus placebo, the difference was borderline not significant (P = .07). However, hot flash scores were equal in the clonidine and venlafaxine groups. Over the course of 12 weeks, the differences between both treatments and placebo were significant (P <.001 for venlafaxine v placebo; P = .045 for clonidine v placebo). Frequencies of treatment-related adverse effects of nausea (P = .02), constipation (P = .04), and severe appetite loss were higher in the venlafaxine group. Venlafaxine and clonidine are effective treatments in the management of hot flashes in patients with breast cancer. Venlafaxine resulted in a more immediate reduction of hot flash scores when compared with clonidine; however, hot flash scores at week 12 were lower in the clonidine group than in the venlafaxine group.

The TU-025 keishibukuryogan clinical trial for hot flash management in postmenopausal women

The aim of this study was to assess the efficacy of TU-025, keishibukuryogan, a Japanese prescription herbal medicine used for hot flash management, in American women. This randomized, double-blind, placebo-controlled, phase II trial enrolled 178 postmenopausal women aged 45 to 58 years with a Mayo hot flash score greater than 28 per week who met other inclusion criteria. After a 1-week placebo run-in period, participants were randomly assigned placebo, or 7.5 g/day, or 12.5 g/day groups, for 12 weeks. Primary and secondary outcomes were measured using the Mayo Clinic Hot Flash Diary, the Greene Climacteric Index, and the Pittsburgh Sleep Quality Index. At 3 months, hot flash scores, climacteric symptoms, and sleep quality improved by 34% in the placebo group, 40% in the 7.5 g/day group, and 38% in the 12.5 g/day group. (P < 0.001). However, the differences in changes between groups were not statistically significant (P = 0.990). Diarrhea unexpectedly developed in 20% of participants receiving active medication. For American women, unlike the clinical experience for Japanese women, TU-025 did not significantly reduce the frequency and severity of hot flash symptoms, improve climacteric symptoms, or benefit sleep quality. This study identified several potentially significant methodological factors to be considered in future scientific assessments of traditional Asian medicines.

Expanded Prostate Cancer Index Composite for Clinical Practice: Development and Validation of a Practical Health Related Quality of Life Instrument for Use in the Routine Clinical Care of Patients With Prostate Cancer

Measuring the health related quality of life of patients with prostate cancer in routine clinical practice is hindered by the lack of instruments enabling efficient, real-time, point of care scoring of multiple health related quality of life domains. Thus, we developed an instrument for this purpose. The Expanded Prostate Cancer Index Composite for Clinical Practice is a 1-page, 16-item questionnaire that we constructed to measure urinary incontinence, urinary irritation, and the bowel, sexual and hormonal health related quality of life domains. We eliminated conceptually overlapping items from the 3-page Expanded Prostate Cancer Index Composite-26 and revised the questionnaire format to mirror the AUA symptom index, thereby enabling practitioners to calculate health related quality of life scores at the point of care. We administered the Expanded Prostate Cancer Index Composite for Clinical Practice to a new cohort of patients with prostate cancer in community based and academic oncology, radiation, and urology practices to evaluate instrument validity as well as ease of use in clinical practice. A total of 175 treated and 132 untreated subjects with prostate cancer completed the Expanded Prostate Cancer Index Composite for Clinical Practice. The domain scores of the Expanded Prostate Cancer Index Composite for Clinical Practice correlated highly with the respective domain scores from longer versions of the Expanded Prostate Cancer Index Composite (r≥0.93 for all domains). The Expanded Prostate Cancer Index Composite for Clinical Practice showed high internal consistency (Cronbach's α 0.64-0.84) and sensitivity to prostate cancer treatment related effects (p<0.05 in each of 5 health related quality of life domains). Patients completed the Expanded Prostate Cancer Index Composite for Clinical Practice efficiently (96% in less than 10 minutes and with 11% missing items). It was deemed very convenient by clinicians in 87% of routine clinical encounters and clinicians accurately scored completed questionnaires 94% of the time. The Expanded Prostate Cancer Index Composite for Clinical Practice is a valid instrument that enables patient reported, health related quality of life to be measured efficiently and accurately at the point of care, and thereby facilitates improved emphasis and management of patient reported outcomes.

Venlafaxine for the Treatment of Hormonal Therapy–Induced Hot Flashes in a Male Patient

To the Editor: Hot flashes are a common problem encountered in men treated with luteinizing hormone releasing hormone agonist therapy (LHRH agonist therapy) in prostate cancer. The prevalence of hot flashes in such men is 50%–80%.1,2 It has been reported to continue for a few months to as long as 5–8 years even after discontinuation of hormones.2 Various hormonal and nonhormonal treatment options have been tried for management of hot flashes for men with prostate cancer on LHRH agonist therapy.3 In a recent randomized controlled trial, venlafaxine has been found to be both efficacious and well tolerated in management of hot flashes in such patients.4 Venlafaxine, even at a low dose of 25 mg, has been found to have a response rate of 63% in the treatment of hot flashes in patients with prostate cancer who were treated with LHRH agonist therapy.5 Here, we present a case of LHRH agonist therapy–induced hot flashes in a prostate cancer patient who was successfully treated with venlafaxine. Case report. Mr A, a 71-year-old white man, was diagnosed in 2005 with adenocarcinoma of the prostate, currently in Gleason 4 + 3, T2b. His past medical history is significant for recurrent coronary artery disease, with angioplasty and stent placement; follicular carcinoma of the thyroid with complete thyroidectomy on suppressive doses of levothyroxine; gastroesophageal reflux disease; B12 deficiency status post cholecystectomy; cataract surgery in both eyes; axial skeleton compression fracture at T8 and then L1; and correction of hypovitaminosis D. His family history is significant for colon cancer in his father and breast cancer in his mother. There is no history of psychiatric illness in the family. His medications at the time of this report were metoprolol-XL 25 mg twice a day, nitroglycerin 0.4 mg sublingual prn; levothyroxine 175 μg/d; tamsulosin hydrochloride 0.4 mg once a day; vitamin B12 500 μg/d; calcium and vitamin D 600 mg/400 units twice per day, pantoprazole sodium 40 mg/d, venlafaxine extended-release 37.5 once a day for hot flashes, and aspirin 325 mg/d. The patient has no known allergies. His prostate carcinoma was first treated with cryosurgery, then with biochemical breakthrough followed by intensity-modulated radiation therapy, brachytherapy, and 2 years of LHRH agonist therapy from July 2007 until August 2009. While on hormonal therapy, the patient started having hot flashes. These were severe to very severe in intensity with a frequency of 8–10 times a day. He described these as distressing and bothersome. He stated that he felt “miserably hot.” On several occasions he experienced flushing of the face and drenching night sweats. His sleep was disrupted due to the hot flashes, and he reported an irritable mood during that time. However, he denied depressed mood, changes in his concentration or energy, or any feelings of hopelessness or worthlessness. His activities of daily living were not affected significantly. He continued to have these symptoms even after the hormonal therapy was discontinued. He was started on venlafaxine 37.5 mg once a day for his hot flashes in September 2009. Seven months after the initiation of venlafaxine, the patient reported remarkable improvement in his symptoms of hot flashes. He had started to notice an improvement in symptoms of hot flashes within the first month of the initiation of venlafaxine. He now has only 2–3 episodes of hot flashes per day, and there is more than a 60% reduction in his hot flashes, including reduction in both frequency and intensity of the symptoms from very severe to mild.6 He states that his mood has also improved over this time. His sleep has improved, and he now sleeps uninterrupted and reports feeling better and rested when he wakes up. He denies any significant side effects with venlafaxine and has tolerated it well. The case highlights that venlafaxine is a safe and efficacious choice for the management of hot flashes in men treated with LHRH agonist therapy for prostate cancer. Even with multiple comorbidities, our patient tolerated venlafaxine quite well and showed a remarkable improvement in his symptoms. Although further studies are needed to corroborate these findings, given the efficacy and the safety profile of venlafaxine, it could be considered as one of the choices for treatment of hot flashes and the associated symptoms in this patient population.

Long-term Chinese herbs decoction administration for management of hot flashes associated with endocrine therapy in breast cancer patients

To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy- associated hot flashes symptom in breast cancer patients. Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups, the control group received endocrine therapy alone, the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy: Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years. Frequency of hot flashes per day was recorded, and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index. Sixty cases were analyzed, 32 cases in endocrine therapy combining Chinese herbs decoction group, 28 cases in mere endocrine therapy group. For hot flashes symptom, in Chinese herbs decoction administration group, 7 cases (21.9%) reported symptom disappeared, 22 cases (68.7%) reported symptom alleviated, 3 cases (9.4%) reported symptom not changed; in endocrine therapy alone group, 5 cases (17.9%) reported symptom disappeared, 13 cases (46.4%) reported symptom alleviated, 10 cases (10/28, 35.7%) reported symptom not changed. The difference between two groups was statistically significant (P=0.013). For sleeping disorder, in Chinese herbs decoction administration group, 27 cases (84.4%) reported symptom improved, 5 cases (15.6%) reported no change; in endocrine therapy alone group, 16 cases (57.1%) symptom improved, 12 cases (42.9%) reported no change in sleeping disorder (P=0.019), the difference was also of significance statistically. Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy, meanwhile without definite toxicity and influence on the risk of recurrence of tumor.

Use of Gabapentin for the Management of Natural or Surgical Menopausal Hot Flashes

To review the literature examining the use of gabapentin for treatment of hot flashes during natural or surgically induced menopause. A literature search was conducted via PubMed, MEDLINE, and International Pharmaceutical Abstracts (1948-November 2010) using the search terms gabapentin, hot flashes, and menopause. Literature was limited to English-language, human studies. Additional material was identified by reviewing reference citations of the articles retrieved. Studies with data describing gabapentin for hot flash management during natural or surgically induced menopause were included. Any studies including women with a history of breast cancer were excluded. Four studies met the inclusion criteria. Gabapentin significantly decreased hot flash frequency and hot flash composite scores by 45-71% from baseline in the 4 trials included in this review. In 2 of the trials, gabapentin was comparable to hormone replacement therapy (71% vs 72%, respectively, p=0.63) in decreasing hot flash composite scores at the end of 12 weeks and in decreasing hot flash frequency at the end of 8 weeks (58.9% vs 70.1%, p>0.05). In all trials, the most common adverse effects with gabapentin were somnolence/drowsiness, unsteadiness, and dizziness. These adverse effects were most pronounced during the first 1-2 weeks of therapy, but resolved and were similar to those reported with placebo by week 4. These trials were short (<12 weeks) and had small sample sizes; however, their results appear to show that gabapentin is safe and effective for short-term treatment of hot flashes in women who have entered menopause either naturally or surgically. Gabapentin 600-2400 mg/day in divided doses may be a viable option for treating hot flashes in menopausal women who do not want to use hormone replacement therapy.

Abstract PD08-04: Management of Hot Flashes in Breast Cancer Patients with Venlafaxine and Clonidine: A Double-Blind Placebo-Controlled Trial

Abstract Background: Therapies for breast cancer may result in symptoms as hot flashes, genitourinary atrophy and psychological distress. Hot flashes are common symptoms that can interfere with quality of life. We undertook a double-blind, placebo controlled trial to assess the efficacy of venlafaxine and clonidine during 12 weeks of treatment. Methods: 102 patients with a history of breast cancer with at least two hot flashes per day were randomly assigned (2:2:1) to venlafaxine 75 mg/d, clonidine 0.1 mg/d or placebo. Daily hot flash scores were recorded at baseline and during treatment. Questionnaires at baseline and during week 4 and 12 assessed sexual function (SAQ), sleep quality (GSQ), anxiety and depression (HADS). The primary endpoint was differences in the average daily hot flash score in the twelfth week between venlafaxine, clonidine and placebo. Secondary objectives were to determine the effect of both drugs on sexual function, sleep quality, anxiety, depression and treatment side effects. Analyses were by intention to treat. Results: 80 patients had evaluable data over the whole study period of 12 weeks. At week 12, treatment was associated with a decrease in the occurrence of hot flashes by 45% versus placebo (p=0.03). There was no significant difference between venlafaxine and clonidine treatment however, over the course of 12 weeks hot flash scores were reduced by 41% in the venlafaxine group and by 26% in the clonidine group (Figure 1). The differences between both treatments and placebo over the 12 week period were significant (p=0.0004 venlafaxine versus placebo, p=0.045 clonidine versus placebo, p=0.002 both treatments versus placebo). Sexual function and sleep quality were not significantly different between the two treatment groups. Adjusting for baseline scores, the week 12 anxiety scores were higher in the clonidine group than in the venlafaxine group (p=0.04) and the depression scores were higher in the venlafaxine group than in the clonidine group (p=0.03). Frequencies of treatment-related side effects, nausea (p=0.02) and constipation (p=0.04) were significantly higher in the venlafaxine group. Only appetite loss (p=0.003) occurred more frequently in the venlafaxine group as severe side effect. Premature discontinuation for adverse events occurred in 2 (5%) patients in the venlafaxine group and 6 (15%) patients in the clonidine group (p=0.26). 41 patients (40%) continued the study treatment after the end of the study. Figure 1. Hot flash score over 12 weeks (blue=placebo, red=clonidine, green=venlafaxine; Discussion: Venlafaxine and clonidine are effective treatments in the management of hot flashes. Venlafaxine treatment resulted in a swifter reduction in the hot flash score in comparison to clonidine. Venlafaxine is more effective than clonidine over the 12 week period of treatment, but at the cost of more side effects. These findings suggest that venlafaxine is to be preferred above clonidine. In case of intolerance clonidine is a realistic treatment alternative. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-04.

Multicenter, Randomized, Cross-Over Clinical Trial of Venlafaxine Versus Gabapentin for the Management of Hot Flashes in Breast Cancer Survivors

Nonhormonal pharmacologic interventions are recommended for the treatment of hot flashes in breast cancer survivors. Antidepressants and gabapentin have been shown to be both effective and well tolerated; however, it is not clear which is preferred. This was a group-sequential, open-label, randomized, cross-over trial of 4 weeks of venlafaxine (37.5 mg daily for 7 days followed by 75 mg daily for 21 days) versus gabapentin (300 mg once per day for 3 days, then 300 mg twice per day for 3 days, then 300 mg three times per day for 22 days), with patient preference as the primary outcome. Postmenopausal women with at least 14 bothersome hot flashes per week for the prior month were eligible. A 2-week baseline period and a 2-week tapering/washout time was used before the first and second treatment periods, respectively. Diaries were used to measure hot flashes and potential toxicities throughout the study. Participants completed a preference questionnaire at the end of the study. A predefined Pocock stopping rule was applied. Patient preference and hot flash and toxicity outcomes were compared between treatments. Sixty-six patients were randomly assigned, 56 of whom provided a preference (eight dropped out and two had no preference); 18 (32%) preferred gabapentin and 38 (68%) preferred venlafaxine (P = .01). Both agents reduced hot flash scores to a similar extent (66% reduction). Venlafaxine was associated with increased nausea, appetite loss, constipation, and reduced negative mood changes compared with gabapentin, whereas gabapentin was associated with increased dizziness and appetite compared with venlafaxine (all P < .05). Breast cancer survivors prefer venlafaxine over gabapentin for treating hot flashes.

Nonhormonal management of hot flashes for women on risk reduction therapy.

Hot flashes are very common in women in menopause and can have a detrimental effect on quality of life. Women on risk reduction therapy are particularly prone because treatments, such as tamoxifen, raloxifene, or oophorectomy, have the potential to exacerbate these symptoms. Hormonal treatments, despite the fact that they represent the most effective therapies, are not used for the treatment of hot flashes in these women because of concerns that they may increase the risk for breast cancer. As a result, several nonhormonal therapies have been tested in randomized placebo-controlled trials and shown to be effective, such as paroxetine, venlafaxine, desvenlafaxine, fluoxetine, citalopram, gabapentin, and pregabalin. In addition, several nonpharmacologic therapies have been tested with various successes. An additional consideration is how some of those drugs, especially fluoxetine and paroxetine, interact with the metabolism of tamoxifen. This article discusses these issues, and provides some recommendations regarding use of nonhormonal therapies for treating hot flashes in women on risk reduction therapy, with an emphasis on pharmacogenomic considerations.

A randomized crossover trial of venlafaxine (V) versus gabapentin (G) for hot flashes (HF) in breast cancer survivors.

9023 Background: Nonhormonal pharmacologic interventions are recommended for the treatment of HF in breast cancer survivors. Antidepressants (SSRI/SNRI) and G have been shown to be effective, however, it is still unclear which agent is best. Methods: A randomized crossover trial compared 4 weeks of V (37.5 mg × 7 days followed by 75 mg/day) and G (300 mg daily × 3 days, 300 mg BID × 3 days then 300 mg TID). Eligibility included postmenopausal women with at least 14 bothersome HF per week for the prior month. A 2-week baseline period was followed by the first treatment period. Crossover to the alternative treatment occurred following a 2 week dose tapering/wash out period. The primary endpoint was patient preference. Secondary endpoints included change from baseline in HF score (frequency × severity) per a prospective daily HF diary, change in HF frequency, QOL, mood and toxicity. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. A two-stage group sequential design was used with the first analysis pre-planned at 66 patients and the second (if needed) at 131, allowing for drop out/indecision rate of 25%. The design had 80% power to detect a shift from equal preference of ≥ 15 % (2 sided type 1 error at 5%). Results: Data analysis after 66 patients showed the pre-defined stopping rule was satisfied. The study arms were well balanced. Of 56 patients with a preference (8 dropped out and 2 had no preference), 18 preferred G and 38 preferred V (32% and 68% respectively; p = 0.01). Both V and G reduced HF scores (66% reduction) and frequency (55% reduction) similarly and significantly. Satisfaction with the preferred treatment was high. V was associated with more appetite loss, nausea and constipation, and less sleeplessness, nervousness, and negative mood changes than at baseline (all p ≤ 0.03) whereas G was associated with more dizziness and increased appetite, and less sleeplessness (all p ≤ 0.004). Conclusions: Breast cancer survivors prefer V over G for the treatment of HF. Both agents are effective in the management of HF based on recorded diary experience. Preference appears to be driven by the balance between effectiveness and tolerance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, GlaxoSmithKline, Novartis, Roche Amgen, AstraZeneca, GlaxoSmithKline, Novartis, Roche AstraZeneca

Gabapentin for the management of hot flashes in prostate cancer survivors: A longitudinal continuation study—NCCTG trial N00CB.

9139 Background: Hot flashes are a common, undesirable complication of androgen-deprivation therapy in men with prostate cancer. A previous randomized trial indicated that gabapentin (900 mg/day) w...

Management of Hot Flashes in Women with Breast Cancer

Hormone-suppression therapies are used for the treatment of breast cancer in the adjuvant and metastatic settings alike. However, side effects-including hot flashes-are frequently reported by patients as a cause of therapy discontinuation. This paper presents an overview of hormonal therapies and the evidence-based management options for hot flashes, summarized in a treatment algorithm.