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Safgren SL, Suman VJ, Leon Ferre RA, Kosel ML, Stearns V, Henry NL, Denduluri N, Irvin W, Ingle JN, Sideras K, Ames MM, Reid JM, Loprinzi CL, Black JL, Weinshilboum RM, Goetz MP. The impact of coadministration of venlafaxine, citalopram or gabapentin on the metabolic activation of tamoxifen. Breast Cancer Res Treat 2025; 211:261-270. [PMID: 40011368 DOI: 10.1007/s10549-025-07644-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 02/09/2025] [Indexed: 02/28/2025]
Abstract
PURPOSE Tamoxifen undergoes metabolic activation by cytochrome P450 (CYP) enzymes to metabolites with more potent anti-estrogenic effects. Numerous studies demonstrate decreased tamoxifen efficacy associated with reduced CYP2D6 activity or lower Z-endoxifen concentrations. Women taking tamoxifen frequently experience vasomotor symptoms (VMS) that may require medical treatment. Many medications used for VMS or depression are CYP substrates that may reduce Z-endoxifen concentrations. While the drug-drug interactions (DDI) from potent CYP2D6 inhibitors (CYPi) on tamoxifen metabolism has been studied, the impact of less potent CYPi including drugs used to treat VMS remains largely unknown. METHODS We performed a prospective trial to evaluate the impact of gabapentin or non-potent CYPi (venlafaxine citalopram) on plasma concentrations of tamoxifen and its metabolites (Z-endoxifen, N-desmethyl-tamoxifen (NDMT) and 4-hydroxy-tamoxifen (4HT). RESULTS Patients enrolled were intermediate to extensive metabolizers by CYP2D6 genotyping. While tamoxifen and NDMT plasma concentrations were not significantly altered, the percent decrease in plasma Z-endoxifen concentration was statistically significant with the addition of venlafaxine (n = 22) or citalopram (n = 18) (median - 14.7 and - 14.4%, respectively) but not with gabapentin (n = 14) (median - 2.3%). A reduction in Z-endoxifen concentrations below the 5.9 ng/ml threshold associated with tamoxifen efficacy was observed in 12% of patients. CONCLUSION The addition of venlafaxine and citalopram but not gabapentin during tamoxifen treatment decreases plasma Z-endoxifen concentrations. SSRIs/SNRIs affecting tamoxifen biotransformation pathways, but with less potent CYPi potential, should be used cautiously in tamoxifen-treated patients and non-CYP inhibiting medications considered when possible.
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Affiliation(s)
- Stephanie L Safgren
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
| | - Vera J Suman
- Division of Quantitative Health Sciences, Department of Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Roberto A Leon Ferre
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
| | - Matthew L Kosel
- Division of Quantitative Health Sciences, Department of Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Vered Stearns
- Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA
| | - N Lynn Henry
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | | | - William Irvin
- Bon Secours Mercy Health, Bon Secours Cancer Institute, Midlothian, VA, USA
| | - James N Ingle
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
| | | | - Matthew M Ames
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
| | - Joel M Reid
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
- Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA
| | - Charles L Loprinzi
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
| | - John L Black
- Division of Laboratory Genetics and Genomics, Personalized Genomics Laboratory, Mayo Clinic Laboratories, Mayo Clinic, Rochester, MN, USA
| | | | - Matthew P Goetz
- Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
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Childs DS, Novotny PJ, Marell PS, Ruddy KJ, Loprinzi CL. Hot flash clinical trial baseline measurements: how long is needed? BMJ Support Palliat Care 2024; 13:e1110-e1116. [PMID: 35477676 DOI: 10.1136/bmjspcare-2022-003681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/06/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Classically, hot flash studies included a baseline period of 1 week or longer. The objective of this study was to compare the accuracy of a 1-day baseline diary to a traditional 1-week diary. METHODS Raw data from 5 pilot studies and 15 phase III randomised controlled trials (RCTs), all of which used a 1-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. RESULTS A total of 2573 participants were included. On average, participants had 8.5 hot flashes per day on day 1. Mean hot flash frequencies and scores on subsequent days (days 2-7) were within 6% of day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Reanalysis for each pilot study revealed that no individual study conclusions would have been altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. CONCLUSIONS A 1-day hot flash diary appears to accurately reflect the true frequency and severity of baseline symptoms in appropriately sized cohorts.
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Affiliation(s)
| | - Paul J Novotny
- Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
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Khan SA. Breast Cancer Risk Reduction: Current Status and Emerging Trends to Increase Efficacy and Reduce Toxicity of Preventive Medication. Surg Oncol Clin N Am 2023; 32:631-646. [PMID: 37714633 DOI: 10.1016/j.soc.2023.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2023]
Abstract
The primary prevention of breast cancer is a worthwhile goal for which the efficacy of antiestrogens is well established. However, implementation has been problematic related to low prioritization by providers and the reluctance of high-risk women to experience medication side effects. Emerging solutions include improved risk estimation through the use of polygenic risk scores and the application of radiomics to screening mammograms; and optimization of medication dose to limit toxicity. The identification of agents to prevent estrogen receptor negative or HER2-positive tumors is being pursued, but personalization of medical risk reduction requires the prediction of tumor subtypes.
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Affiliation(s)
- Seema Ahsan Khan
- Department of Surgery, Feinberg School of Medicine of Northwestern University, 303 East Superior Street, Chicago, IL 60614, USA.
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Loprinzi CL, Novotny P, Ruddy KJ, Jatoi A, Le-Rademacher J, Ehlers SL, Cathcart-Rake E, Lee M. Measuring symptoms and toxicities: a 35-year experience. Support Care Cancer 2023; 31:495. [PMID: 37498410 DOI: 10.1007/s00520-023-07958-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 07/20/2023] [Indexed: 07/28/2023]
Abstract
PURPOSE When conducting trials aimed at the improvement of cancer-related and/or cancer treatment-related toxicities, it is important to determine the best means of measuring patients' symptoms. METHODS The authors of this current manuscript have an extensive experience with the conduct of symptom-control clinical trials. This experience is utilized to provide insight into the best means of measuring symptoms caused by cancer and/or cancer therapy. RESULTS Patient-reported outcome data are preferable for measuring bothersome symptoms, for determining toxicities caused by treatment approaches, and offer more accurate and detailed information compared with health care practitioners recording their impressions of patient experiences. Well-validated patient friendly measures are recommended when they are available. When such are not readily available, face-valid, single-item numerical rating scales are effective instruments to document both treatment trial outcomes and cancer treatment side effects/toxicities. CONCLUSION The use of numerical rating scales are effective means of measuring symptoms caused by cancer, by cancer treatments, and/or alleviated by symptom control treatment approaches.
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Affiliation(s)
| | - Paul Novotny
- Mayo Clinic Rochester (Division of Clinical Trials and Biostatistics), Rochester, MN, USA
| | - Kathryn J Ruddy
- Mayo Clinic Rochester (Medical Oncology), Rochester, MN, USA
| | - Aminah Jatoi
- Mayo Clinic Rochester (Medical Oncology), Rochester, MN, USA
| | - Jennifer Le-Rademacher
- Mayo Clinic Rochester (Division of Clinical Trials and Biostatistics), Rochester, MN, USA
| | - Shawna L Ehlers
- Mayo Clinic Rochester (Psychiatry & Psychology), Rochester, MN, USA
| | | | - Minji Lee
- Mayo Clinic Rochester (Division of Clinical Trials and Biostatistics), Rochester, MN, USA
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Ye L, Knox B, Hickey M. Management of Menopause Symptoms and Quality of Life during the Menopause Transition. Endocrinol Metab Clin North Am 2022; 51:817-836. [PMID: 36244695 DOI: 10.1016/j.ecl.2022.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Some women experience bothersome symptoms around the time of menopause that may have a negative impact on their quality of life and prompt them to seek treatments. Menopausal hormone therapy was historically the treatment of choice. However, medical contraindications and personal preference for nonhormonal therapy have prompted the evaluation of a range of nonhormonal pharmacologic and non-pharmacologic therapies. This review provides an update focusing on the latest evidence-based approach for the management of bothersome symptoms of menopause.
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Affiliation(s)
- Louie Ye
- The Royal Women's Hospital, 20 Flemington Road, Melbourne, Victoria 3052, Australia; The Department of Obstetrics and Gynaecology, University of Melbourne and the Royal Women's Hospital, Lv 7 20 Flemington Road, Melbourne, Victoria 3052, Australia
| | - Benita Knox
- The Royal Women's Hospital, 20 Flemington Road, Melbourne, Victoria 3052, Australia
| | - Martha Hickey
- The Royal Women's Hospital, 20 Flemington Road, Melbourne, Victoria 3052, Australia; The Department of Obstetrics and Gynaecology, University of Melbourne and the Royal Women's Hospital, Lv 7 20 Flemington Road, Melbourne, Victoria 3052, Australia.
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Cole KM, Clemons M, McGee S, Alzahrani M, Larocque G, MacDonald F, Liu M, Pond GR, Mosquera L, Vandermeer L, Hutton B, Piper A, Fernandes R, Emam KE. Using machine learning to predict individual patient toxicities from cancer treatments. Support Care Cancer 2022; 30:7397-7406. [PMID: 35614153 PMCID: PMC9385785 DOI: 10.1007/s00520-022-07156-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 05/16/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE Machine learning (ML) is a powerful tool for interrogating datasets and learning relationships between multiple variables. We utilized a ML model to identify those early breast cancer (EBC) patients at highest risk of developing severe vasomotor symptoms (VMS). METHODS A gradient boosted decision model utilizing cross-sectional survey data from 360 EBC patients was created. Seventeen patient- and treatment-specific variables were considered in the model. The outcome variable was based on the Hot Flush Night Sweats (HFNS) Problem Rating Score, and individual scores were dichotomized around the median to indicate individuals with high and low problem scores. Model accuracy was assessed using the area under the receiver operating curve, and conditional partial dependence plots were constructed to illustrate relationships between variables and the outcome of interest. RESULTS The model area under the ROC curve was 0.731 (SD 0.074). The most important variables in the model were as follows: the number of hot flashes per week, age, the prescription, or use of drug interventions to manage VMS, whether patients were asked about VMS in routine follow-up visits, and the presence or absence of changes to breast cancer treatments due to VMS. A threshold of 17 hot flashes per week was identified as being more predictive of severe VMS. Patients between the ages of 49 and 63 were more likely to report severe symptoms. CONCLUSION Machine learning is a unique tool for predicting severe VMS. The use of ML to assess other treatment-related toxicities and their management requires further study.
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Affiliation(s)
- Katherine Marie Cole
- Department of Medicine, Division of Medical Oncology, The University of Ottawa, Ottawa, Canada
| | - Mark Clemons
- Department of Medicine, Division of Medical Oncology, The University of Ottawa, Ottawa, Canada
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Sharon McGee
- Department of Medicine, Division of Medical Oncology, The University of Ottawa, Ottawa, Canada
| | - Mashari Alzahrani
- Department of Medicine, Division of Medical Oncology, The University of Ottawa, Ottawa, Canada
| | | | | | - Michelle Liu
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Gregory R Pond
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Lucy Mosquera
- CHEO Research Institute, University of Ottawa, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada
| | - Lisa Vandermeer
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Brian Hutton
- Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Ardelle Piper
- University of Ottawa Health Services, Ottawa, ON, Canada
| | - Ricardo Fernandes
- Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada
| | - Khaled El Emam
- CHEO Research Institute, University of Ottawa, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
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7
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Cole KM, Clemons M, Alzahrani M, Liu M, Larocque G, MacDonald F, Hutton B, Piper A, Fernandes R, Pond GR, Vandermeer L, Emam KE, McGee SF. Vasomotor symptoms in early breast cancer-a "real world" exploration of the patient experience. Support Care Cancer 2022; 30:4437-4446. [PMID: 35112212 PMCID: PMC8809216 DOI: 10.1007/s00520-022-06848-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/18/2022] [Indexed: 11/20/2022]
Abstract
BACKGROUND Despite the frequency of vasomotor symptoms (VMS) in patients with early breast cancer (EBC), their optimal management remains unknown. A patient survey was performed to determine perspectives on this important clinical challenge. METHODS Patients with EBC experiencing VMS participated in an anonymous survey. Patients reported on the frequency and severity of VMS using the validated Hot Flush Rating Scale (HFRS) and ranked their most bothersome symptoms. Respondents were also asked to determine endpoints that defined effective treatment of VMS and report on the effectiveness of previously tried interventions. RESULTS Responses were received from 373 patients, median age 56 years (range 23-83), who experienced an average of 5.0 hot flashes per day (SD 6.57). Patients reported the most bothersome symptoms to be feeling hot/sweating (155/316, 49%) and sleeping difficulties (86/316, 27%). Fifty-five percent (201/365) of patients would consider a treatment to be effective if it reduced night-time awakenings. While 68% of respondents were interested in trying interventions from their healthcare team to manage VMS, only 18% actually did so. Of the 137 patients who had tried an intervention for VMS, pharmacological treatments, exercise, and relaxation strategies were more likely to be effective, while therapies such as melatonin and black cohosh were deemed less effective. CONCLUSION VMS are a common and bothersome problem for EBC patients, with a minority receiving interventions to manage these symptoms. Further research is needed to identify patient-centered strategies for managing these distressing symptoms.
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Affiliation(s)
- Katherine Marie Cole
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Mark Clemons
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Mashari Alzahrani
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Michelle Liu
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Gail Larocque
- The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada
| | | | - Brian Hutton
- Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Ardelle Piper
- University of Ottawa Health Services, Ottawa, ON, Canada
| | - Ricardo Fernandes
- Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada
| | - Gregory R Pond
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Lisa Vandermeer
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Khaled El Emam
- CHEO Research Institute and the School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Sharon F McGee
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
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Donohoe F, O'Meara Y, Roberts A, Comerford L, Kelly CM, Walshe JM, Peate M, Hickey M, Brennan DJ. The menopause after cancer study (MACS) - A multimodal technology assisted intervention for the management of menopausal symptoms after cancer - Trial protocol of a phase II study. Contemp Clin Trials Commun 2021; 24:100865. [PMID: 34869938 PMCID: PMC8626829 DOI: 10.1016/j.conctc.2021.100865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 10/06/2021] [Accepted: 11/09/2021] [Indexed: 11/13/2022] Open
Abstract
Aims This study will aim to assess if a composite intervention which involves a specific evidence-based intervention for management of insomnia and non-hormonal pharmacotherapy to manage vasomotor symptoms (VMS) of menopause can improve quality of life for patients experiencing troublesome VMS after cancer who are not eligible for standard systemic menopausal hormone therapy (MHT). Participants will be asked to nominate a partner or companion to support them during this process as an additional form of support. Background The menopause transition and its symptoms represent a significant challenge for many patients after cancer treatment, particularly those for whom conventional MHT is contraindicated. These symptoms include hot flushes, night sweats, urogenital symptoms as well as mood and sleep disturbance. These symptoms can exacerbate the consequences of cancer and its treatment. Methods We will recruit 205 women who meet inclusion criteria and enrol them on a composite intervention which consists of four parts: (1) use of non-hormonal pharmacotherapy for the management of troublesome vasomotor symptoms of menopause tailored to the timing of predominant symptoms, (2) digital cognitive behavioural therapy for insomnia through the web based Sleepio service, (3) access to information regarding self-management strategies for the common symptoms of menopause and their consequences and (4) identification of a partner or other support person who commits to providing support during the study period. Outcomes The primary outcome will be cancer specific quality of life measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). Secondary outcomes will include sleep quality, bother/interference of vasomotor symptoms and communication between couples about their cancer diagnosis and their menopause experience. Sleep will be measured using the Sleep Condition Indicator (SCI) tool, bother/interference of vasomotor symptoms will be measured by the Hot Flush Rating Scale (HFRS) and communication will be measured using the Couples’ Illness Communication Scale (CICS). These validated scales will be administered at baseline, four weeks, three months and six months. Registration This study is registered on ClinicalTrials.gov with number NCT 04766229.
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Affiliation(s)
- Fionán Donohoe
- UCD Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
| | - Yvonne O'Meara
- UCD Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
| | - Aidin Roberts
- UCD Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
| | - Louise Comerford
- UCD Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
| | - Catherine M Kelly
- Dept. of Medical Oncology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
| | - Janice M Walshe
- Dept. of Medical Oncology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Michelle Peate
- Dept. of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Victoria, Australia
| | - Martha Hickey
- Dept. of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Victoria, Australia
| | - Donal J Brennan
- UCD Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
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Hutton B, Hersi M, Cheng W, Pratt M, Barbeau P, Mazzarello S, Ahmadzai N, Skidmore B, Morgan SC, Bordeleau L, Ginex PK, Sadeghirad B, Morgan RL, Cole KM, Clemons M. Comparing Interventions for Management of Hot Flashes in Patients With Breast and Prostate Cancer: A Systematic Review With Meta-Analyses. Oncol Nurs Forum 2021; 47:E86-E106. [PMID: 32555553 DOI: 10.1188/20.onf.e86-e106] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PROBLEM IDENTIFICATION Hot flashes are common and bothersome in patients with breast and prostate cancer and can adversely affect patients' quality of life. LITERATURE SEARCH Databases were searched for randomized controlled trials (RCTs) evaluating the effects of one or more interventions for hot flashes in patients with a history of breast or prostate cancer. DATA EVALUATION Outcomes of interest included changes in hot flash severity, hot flash frequency, quality of life, and harms. Pairwise meta-analyses and network meta-analyses were performed where feasible, with narrative synthesis used where required. SYNTHESIS 40 RCTs were included. Findings from network meta-analysis for hot flash frequency suggested that several therapies may offer benefits compared to no treatment, but little data suggested differences between active therapies. Findings from network meta-analysis for hot flash score were similar. IMPLICATIONS FOR RESEARCH Although many interventions may offer improvements for hot flashes versus no treatment, minimal data suggest important differences between therapies. SUPPLEMENTARY MATERIALS CAN BE FOUND BY VISITING HTTPS //bit.ly/2WGzi30.
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Santen RJ, Heitjan DF, Gompel A, Lumsden MA, Pinkerton JV, Davis SR, Stuenkel CA. Approach to Managing a Postmenopausal Patient. J Clin Endocrinol Metab 2020; 105:5901131. [PMID: 32882039 DOI: 10.1210/clinem/dgaa623] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 08/31/2020] [Indexed: 12/23/2022]
Abstract
The case of a symptomatic, postmenopausal woman is presented and a full discussion of the approach to her management is discussed. Pertinent guidelines and scientific evidence are emphasized as support for the recommendations.
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Affiliation(s)
- Richard J Santen
- University of Virginia Health System, Division of Endocrinology & Metabolism and Obstetrics & Gynecology, Charlottesville, Virginia
| | - Daniel F Heitjan
- Southern Methodist University Department of Statistical Science and University of Texas Southwestern Department of Population & Data Sciences, Dallas, Texas
| | - Anne Gompel
- Université Paris Descartes, Gynecologie Endocrinienne, Paris, France
| | | | - JoAnn V Pinkerton
- University of Virginia Health System, Division of Endocrinology & Metabolism and Obstetrics & Gynecology, Charlottesville, Virginia
| | - Susan R Davis
- Monash University, School of Public Health and Preventative Medicine, Melbourne, Australia
| | - Cynthia A Stuenkel
- University of California San Diego, School of Medicine, Division of Endocrinology and Metabolism, La Jolla, California
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Kaplan M, Ginex PK, Michaud LB, Fernández-Ortega P, Leibelt J, Mahon S, Rapoport BL, Robinson V, Maloney C, Moriarty KA, Vrabel M, Morgan RL. ONS Guidelines™ for Cancer Treatment-Related Hot Flashes in Women With Breast Cancer and Men With Prostate Cancer. Oncol Nurs Forum 2020; 47:374-399. [PMID: 32555554 DOI: 10.1188/20.onf.374-399] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE Hot flashes are a common and troublesome side effect of surgery or endocrine therapy. They may lead to physical and psychological distress and negatively affect quality of life. This clinical practice guideline presents evidence-based recommendations for pharmacologic, behavioral, and natural health product interventions for treatment-related hot flashes in patients with breast or prostate cancer. METHODOLOGIC APPROACH An interprofessional panel of healthcare professionals with patient representation prioritized clinical questions and patient outcomes for the management of hot flashes. Systematic reviews of the literature were conducted. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to assess the evidence and make recommendations. FINDINGS The panel agreed on 14 pharmacologic, behavioral, and natural health recommendations. IMPLICATIONS FOR NURSING Conditional recommendations include the use of antidepressants rather than no treatment, physical activity rather than no treatment, and the avoidance of gabapentin and dietary supplements in the treatment of hot flashes. SUPPLEMENTARY MATERIAL CAN BE FOUND AT HTTPS //onf.ons.org/ons-guidelines-hot-flashes-supplementary-material.
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Shan D, Zou L, Liu X, Shen Y, Cai Y, Zhang J. Efficacy and safety of gabapentin and pregabalin in patients with vasomotor symptoms: a systematic review and meta-analysis. Am J Obstet Gynecol 2020; 222:564-579.e12. [PMID: 31870736 DOI: 10.1016/j.ajog.2019.12.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 12/10/2019] [Accepted: 12/14/2019] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Vasomotor symptoms are common among postmenopausal women and patients receiving hormone deprivation therapies, and emerging studies are exploring gabapentin's and pregabalin's effects as nonhormonal treatment options. We aimed to assess the efficacy and safety of these 2 drugs. DATA SOURCES Based on a preregistered protocol (Prospective Register of Systematic Reviews -CRD42019133650), we searched 10 databases (PubMed, Embase, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese Biological Medical Literature, Chinese National Knowledge Infrastructure, Chinese Journals Full-text Database [VIP], and Wanfang) as well as the World Health Organization international clinical trials registry platform and reference lists of related literatures. STUDY ELIGIBILITY CRITERIA Randomized controlled trials and randomized crossover studies exploring gabapentin and pregabalin among women patients with vasomotor symptoms were included. STUDY APPRAISAL AND SYNTHESIS METHODS The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. Two reviewers independently selected studies, assessed bias, and extracted data. Mean difference and standardized mean difference with 95% confidence intervals were assessed by random-effects models. Heterogeneities were assessed by I2 statistics, and the quality of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Nineteen randomized controlled trials and 2 randomized crossover trials reporting results from 3519 participants were included. Gabapentin could reduce hot flash frequency (mean difference, -1.62, 95% confidence interval, -1.98 to -1.26 after 4 weeks; mean difference, -2.77, 95% confidence interval, -4.29 to -1.24 after 12 weeks) and composite score (standardized mean difference, -0.47, 95% confidence interval, -0.71 to -0.23 after 4 weeks; standardized mean difference, -0.77, 95% confidence interval, -1.15 to -0.40 after 12 weeks) compared with placebo. Both menopausal participants and patients with breast cancer benefited from treatment. Higher risks of dizziness and somnolence were found in the gabapentin group than in the control group (risk ratio, 4.45, 95% confidence interval, 2.50-7.94; risk ratio, 3.29, 95% confidence interval, 1.97-5.48, respectively). Estrogen was more effective in reducing hot flash frequency than gabapentin. No statistically significant difference in reduction of hot flash severity score was found between gabapentin and antidepressants. The trials comparing gabapentin or pregabalin with the other interventions were too limited to make a conclusion. CONCLUSION Favorable effects of gabapentin in relieving vasomotor symptoms were observed, compared with controls, but were less effective than those of estrogen. Evidence supporting the therapeutic effect of pregabalin is still lacking.
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Leon-Ferre RA, Novotny PJ, Wolfe EG, Faubion SS, Ruddy KJ, Flora D, Dakhil CSR, Rowland KM, Graham ML, Le-Lindqwister N, Smith TJ, Loprinzi CL. Oxybutynin vs Placebo for Hot Flashes in Women With or Without Breast Cancer: A Randomized, Double-Blind Clinical Trial (ACCRU SC-1603). JNCI Cancer Spectr 2020; 4:pkz088. [PMID: 32337497 PMCID: PMC7050158 DOI: 10.1093/jncics/pkz088] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/12/2019] [Accepted: 10/17/2019] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Hot flashes (HFs) negatively affect quality of life among perimenopausal and postmenopausal women. This study investigated the efficacy of oxybutynin vs placebo in decreasing HFs. METHODS In this randomized, multicenter, double-blind study, women with and without breast cancer with 28 or more HFs per week, lasting longer than 30 days, who were not candidates for estrogen-based therapy, were assigned to oral oxybutynin (2.5 mg twice a day or 5 mg twice a day) or placebo for 6 weeks. The primary endpoint was the intrapatient change from baseline in weekly HF score between each oxybutynin dose and placebo using a repeated-measures mixed model. Secondary endpoints included changes in weekly HF frequency, HF-related daily interference scale questionnaires, and self-reported symptoms. RESULTS We enrolled 150 women. Baseline characteristics were well balanced. Mean (SD) age was 57 (8.2) years. Two-thirds (65%) were taking tamoxifen or an aromatase inhibitor. Patients on both oxybutynin doses reported greater reductions in the weekly HF score (5 mg twice a day: -16.9 [SD 15.6], 2.5 mg twice a day: -10.6 [SD 7.7]), placebo -5.7 (SD 10.2); P < .005 for both oxybutynin doses vs placebo), HF frequency (5 mg twice a day: -7.5 [SD 6.6], 2.5 mg twice a day: -4.8 [SD 3.2], placebo: -2.6 [SD 4.3]; P < .003 for both oxybutynin doses vs placebo), and improvement in most HF-related daily interference scale measures and in overall quality of life. Patients on both oxybutynin arms reported more side effects than patients on placebo, particularly dry mouth, difficulty urinating, and abdominal pain. Most side effects were grade 1 or 2. There were no differences in study discontinuation because of adverse effects. CONCLUSION Oxybutynin is an effective and relatively well-tolerated treatment option for women with HFs.
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Affiliation(s)
| | - Paul J Novotny
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Eric G Wolfe
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | | | | | - Daniel Flora
- Oncology/Hematology, St. Elizabeth Physicians, Crestview Hills, KY
| | | | | | - Mark L Graham
- Medical Oncology, Waverly Hematology/Oncology, Cary, NC
| | | | - Thomas J Smith
- Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD
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No Author. Chapitre 4 : Symptômes vasomoteurs. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2019; 41 Suppl 1:S68-S72. [DOI: 10.1016/j.jogc.2019.02.143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Affiliation(s)
- J. V. Pinkerton
- Division of Midlife Health, University of Virginia Health System, Charlottesville, VA, USA
| | - R. J. Santen
- Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, VA, USA
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Stark SS, Natarajan L, Chingos D, Ehren J, Gorman JR, Krychman M, Kwan B, Mao JJ, Myers E, Walpole T, Pierce JP, Su HI. Design of a randomized controlled trial on the efficacy of a reproductive health survivorship care plan in young breast cancer survivors. Contemp Clin Trials 2019; 77:27-36. [PMID: 30553078 PMCID: PMC6754982 DOI: 10.1016/j.cct.2018.12.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 12/01/2018] [Accepted: 12/10/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. RESULTS Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5-90.7%) and confidence (50.0-74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. CONCLUSION Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management.
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Affiliation(s)
- Shaylyn S Stark
- Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr. La Jolla, CA 92093-090, USA.
| | - Loki Natarajan
- Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr. La Jolla, CA 92093-090, USA; Department of Family Medicine and Public Health, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0628, USA.
| | - Diana Chingos
- Patient Advocate & Representative, Young Survival Coalition, 10995 Wrightwood Lane, Studio City, CA 91604, USA
| | - Jennifer Ehren
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, 172 Fitzpatrick Hall, Notre Dame, IN 46556-5637, USA.
| | - Jessica R Gorman
- School of Social and Behavioral Health Sciences, Oregon State University College of Public Health and Human Sciences, 160 SW 26(th) St, Corvallis, OR 97331, USA.
| | - Michael Krychman
- Southern California Center for Sexual Health and Survivorship Medicine, 1501 Superior Ave, Suite 201, Newport Beach, CA 92663, USA
| | - Brian Kwan
- Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr. La Jolla, CA 92093-090, USA.
| | - Jun J Mao
- Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
| | - Emily Myers
- Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr. La Jolla, CA 92093-090, USA.
| | - Tom Walpole
- Trials.ai, 4250 Executive Square Suite 200, La Jolla, CA 92037, USA.
| | - John P Pierce
- Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr. La Jolla, CA 92093-090, USA; Department of Family Medicine and Public Health, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0628, USA.
| | - H Irene Su
- Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Dr. La Jolla, CA 92093-090, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, 9300 Campus Pointe Drive, MC 7433, La Jolla, CA 92037, USA.
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Vaz-Luis I, Partridge AH. Exogenous reproductive hormone use in breast cancer survivors and previvors. Nat Rev Clin Oncol 2018; 15:249-261. [DOI: 10.1038/nrclinonc.2017.207] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Management of hot flashes in women with breast cancer receiving ovarian function suppression. Cancer Treat Rev 2017; 52:82-90. [DOI: 10.1016/j.ctrv.2016.11.012] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 11/25/2016] [Accepted: 11/26/2016] [Indexed: 11/18/2022]
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Gradishar WJ. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Cancer Manag Res 2016; 8:85-94. [PMID: 27468248 PMCID: PMC4946864 DOI: 10.2147/cmar.s98249] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed.
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Affiliation(s)
- William J Gradishar
- Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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20
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Singhal SR, Shullai WK. Comparative study of gabapentin and isoflavone in menopausal vasomotor symptoms. J Midlife Health 2016; 7:132-139. [PMID: 27721641 PMCID: PMC5051233 DOI: 10.4103/0976-7800.191017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE This study was planned to compare the effects of gabapentin and isoflavones in menopausal vasomotor symptoms. MATERIALS AND METHODS This prospective comparative study was conducted on 100 patients with complaints of hot flashes, divided into two groups of 50 each. Group I received 900 mg of gabapentin and Group II received 60 mg of isoflavones daily for 3 months. The patients were interviewed to calculate hot flash, global and depression scores and were rescored after 2, 4, 8, and 12 weeks. The primary outcome measure was a change in the hot flash score from baseline. The secondary outcome was an improvement in sleep, depression, and lipid profile. Data were analyzed using Chi-square test and Student's t-test. RESULTS Both groups showed significant improvement in hot flash score at the end of 12 weeks (82% Group I, 74% Group II; P = 0.076). Statistically significant difference was seen at 12 weeks in sleep quality in favor of gabapentin (P = 0.011) and in depression in favor of isoflavones (0.026). Isoflavone had significant improvement in cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides profiles after 12 weeks (P < 0.001, 0.009, 0.024 and <0.001, respectively) as compared to gabapentin. CONCLUSION Isoflavone and gabapentin are equally effective in the treatment of hot flashes; however, isoflavones have better response in patients who have associated with complaints of depression and gabapentin is better who have associated sleep disturbance.
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Affiliation(s)
- Savita Rani Singhal
- Department of obstetrics and Gynecology, Pt. B D Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
| | - Wansalan Kuru Shullai
- Department of obstetrics and Gynecology, Pt. B D Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
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Abstract
Objective Sleep disturbances are common among women in midlife; prevalence increases among perimenopausal/postmenopausal women with vasomotor symptoms. Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the United States for moderate to severe vasomotor symptoms associated with menopause. In two pivotal phase 3 studies evaluating its efficacy and safety, improvements in sleep disturbances were also prospectively evaluated. Methods Postmenopausal women with moderate to severe vasomotor symptoms were randomly assigned to paroxetine 7.5 mg (n = 591) or placebo (n = 593) once daily for 12 weeks (both studies) or 24 weeks (24-wk study). Predefined assessments on weeks 4, 12, and 24 included number of nighttime awakenings attributed to vasomotor symptoms, sleep-onset latency, sleep duration, and sleep-related adverse events. The two studies’ data for weeks 1 to 12 were pooled. Results At baseline, participants reported a mean of 3.6 awakenings/night attributed to vasomotor symptoms. Nighttime awakenings attributed to vasomotor symptoms were significantly reduced within 4 weeks of initiating paroxetine 7.5 mg treatment (39% reduction vs 28% for placebo; P = 0.0049), and reductions were sustained through 12 or 24 weeks of treatment. Paroxetine 7.5 mg treatment also significantly increased nighttime sleep duration (week 4, +31 vs +16 min for placebo; P = 0.0075), but no significant between-group differences in sleep-onset latency or sleep-related adverse events such as sedation were observed. Conclusions In postmenopausal women treated for menopausal vasomotor symptoms, paroxetine 7.5 mg significantly reduces the number of nighttime awakenings attributed to vasomotor symptoms and increases sleep duration without differentially affecting sleep-onset latency or sedation.
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Agarwal N, Singh S, Kriplani A, Bhatla N, Singh N. Safety and efficacy of gabapentin in management of psychosomatic and sexual symptoms in postmenopausal women: A pilot study. J Midlife Health 2015; 6:10-5. [PMID: 25861202 PMCID: PMC4389378 DOI: 10.4103/0976-7800.153605] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Objective: To evaluate safety and efficacy of gabapentin in management of psychosexual symptoms in postmenopausal women. Materials and Methods: Fifty symptomatic postmenopausal females were randomly allocated into two groups; Group I received gabapentin 900 mg/day along with calcium 500 mg and Group II was given only calcium for 6 months and followed-up at 1,3, and 6 months. Data was analyzed in terms of percentage reduction of psychosomatic and sexual symptoms. Change in lipid profile and other blood parameters by the end of study were measured. Results: Maximum improvement was seen in insomnia (90-98%) in gabapentin group. Improvement in anxiety was noted by 40.5, 49.5, and 53.8% at 1, 3, and 6 months, respectively, in Group I. While in Group II, maximum improvement noted was 18.6, 19.7, and 20% at 1, 3, and 6 months, respectively. Similarly for depression, improvement was 40.4,47, and 49.5%at 1, 3, and 6 months, respectively, in Group I; while it was 15.4, 16.6, and 17% at 1, 3, and 6 months, respectively, in Group II. No significant improvement in vaginal dryness and dyspareunia noted at all follow-ups in either group. Somatic symptoms reduced by 33, 36.8, and 40% at 1, 3, and 6 months, respectively, in Group I compared to 18% improvement at all follow-up in Group II. Low density lipoprotein (LDL) was raised in Group I significantly more than Group II. Other blood parameters were comparable in both groups. Conclusion: Gabapentin can lead to improvement in postmenopausal psychosomatic symptoms, while sexual symptoms show no improvement. Gabapentin can lead to increase in serum LDL, hence, precaution should be taken in patients with deranged lipid profile before starting therapy and it should be monitored during course of therapy. This drug can cause minor side effects like somnolence and dizziness.
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Affiliation(s)
- Nutan Agarwal
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Smita Singh
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Alka Kriplani
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Neerja Bhatla
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Nilanchali Singh
- Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
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Drewe J, Bucher KA, Zahner C. A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients. SPRINGERPLUS 2015; 4:65. [PMID: 25713759 PMCID: PMC4331402 DOI: 10.1186/s40064-015-0808-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Accepted: 01/09/2015] [Indexed: 12/03/2022]
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 points
Several 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.
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Affiliation(s)
- Juergen Drewe
- Max Zeller AG, Seeblickstr. 4, 8590 Romanshorn, Switzerland
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Casey PM, Faubion SS, MacLaughlin KL, Long ME, Pruthi S. Caring for the breast cancer survivor’s health and well-being. World J Clin Oncol 2014; 5:693-704. [PMID: 25302171 PMCID: PMC4129533 DOI: 10.5306/wjco.v5.i4.693] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Revised: 04/25/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
The breast cancer care continuum entails detection, diagnosis, treatment, and survivorship. During this time, focus on the whole woman and medical concerns beyond the breast cancer diagnosis itself is essential. In this comprehensive review, we critically review and evaluate recent evidence regarding several topics pertinent to and specific for the woman living with a prior history of breast cancer. More specifically, we discuss the most recent recommendations for contraceptive options including long-acting reversible contraception and emergency contraception, fertility and pregnancy considerations during and after breast cancer treatment, management of menopausal vasomotors symptoms and vulvovaginal atrophy which often occurs even in young women during treatment for breast cancer. The need to directly query the patient about these concerns is emphasized. Our focus is on non-systemic hormones and non-hormonal options. Our holistic approach to the care of the breast cancer survivor includes such preventive health issues as sexual and bone health,which are important in optimizing quality of life. We also discuss strategies for breast cancer recurrence surveillance in the setting of a prior breast cancer diagnosis. This review is intended for primary care practitioners as well as specialists caring for female breast cancer survivors and includes key points for evidence-based best practice recommendations.
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RETIRED: Managing Menopause Chapter 4 Vasomotor Symptoms. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2014. [DOI: 10.1016/s1701-2163(15)30460-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Barba M, Pizzuti L, Sergi D, Maugeri-Saccà M, Vincenzoni C, Conti F, Tomao F, Vizza E, Di Lauro L, Di Filippo F, Carpano S, Mariani L, Vici P. Hot flushes in women with breast cancer: state of the art and future perspectives. Expert Rev Anticancer Ther 2013; 14:185-98. [DOI: 10.1586/14737140.2013.856271] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Zelnak AB. Special considerations in early-stage breast cancer patients and survivors. Obstet Gynecol Clin North Am 2013; 40:573-82. [PMID: 24021258 DOI: 10.1016/j.ogc.2013.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Long-term outcomes for early-stage breast cancer have continued to improve, and more patients are becoming long-term survivors. In addition to patients' concern about risk of developing recurrent disease, they are also concerned about potential toxicities of treatment. Current guidelines for long-term follow-up are reviewed. Potential toxicities of tamoxifen and aromatase inhibitors are reviewed. Management of menopausal symptoms, cancer-related fatigue, and cognitive function is discussed.
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Affiliation(s)
- Amelia B Zelnak
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, 1365 Clifton Road Northeast, Atlanta, GA 30322, USA.
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MacLaughlan David S, Salzillo S, Bowe P, Scuncio S, Malit B, Raker C, Gass JS, Granai CO, Dizon DS. Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study. BMJ Open 2013; 3:e003138. [PMID: 24022390 PMCID: PMC3773636 DOI: 10.1136/bmjopen-2013-003138] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). DESIGN Prospective randomised trial. SETTING Breast health centre of a tertiary care centre. PARTICIPANTS 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. INTERVENTIONS Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. OUTCOME MEASURES The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). RESULTS 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. CONCLUSIONS Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. TRIAL REGISTRATION clinicaltrials.gov (NCT00711529).
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Affiliation(s)
- Shannon MacLaughlan David
- Department of Obstetrics and Gynecology, Stanford Women's Cancer Center, Stanford University, Stanford, California, USA
| | - Sandra Salzillo
- Program in Women's Oncology, Women & Infants Hospital, Alpert Medical School at Brown University, Providence, Rhode Island, USA
| | - Patrick Bowe
- Providence Hypnosis Center, Providence, Rhode Island, USA
| | - Sandra Scuncio
- Program in Women's Oncology, Women & Infants Hospital, Alpert Medical School at Brown University, Providence, Rhode Island, USA
| | - Bridget Malit
- Department of Pediatrics, Weill Cornell Medical College of Cornell University, New York, New York, USA
| | - Christina Raker
- Program in Women's Oncology, Women & Infants Hospital, Alpert Medical School at Brown University, Providence, Rhode Island, USA
| | - Jennifer S Gass
- Program in Women's Oncology, Women & Infants Hospital, Alpert Medical School at Brown University, Providence, Rhode Island, USA
| | - C O Granai
- Program in Women's Oncology, Women & Infants Hospital, Alpert Medical School at Brown University, Providence, Rhode Island, USA
| | - Don S Dizon
- Department of Internal Medicine, Massachusetts General Hospital, Harvard University, Boston, Massachusetts, USA
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Yadav M, Volkar J. Potential role of gabapentin and extended-release gabapentin in the management of menopausal hot flashes. Int J Gen Med 2013; 6:657-64. [PMID: 23950657 PMCID: PMC3742343 DOI: 10.2147/ijgm.s45880] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
About 80% of postmenopausal women experience vasomotor symptoms, such as hot flashes and night sweats – symptoms that are associated with sleep disruption and can lead to fatigue and mood changes. Moreover, hot flashes can be embarrassing for women, causing difficulties at work and in their social lives. Many therapies have been advocated for relief of vasomotor symptoms, but only hormone therapy has been US Food and Drug Administration approved. However, after the Women’s Health Initiative Study suggested that there was a correlation between hormone therapy and increased risk for breast cancer and cardiovascular events, many women stopped taking hormone therapy, and many do not want to initiate it. Hormone therapy is also contraindicated in certain women, such as those with a history of hormone-stimulated cancer like breast and uterine cancer. Gabapentin (Neurontin) has shown efficacy in relieving vasomotor symptoms and is used as off-label for this indication. A new extended-release formulation of gabapentin has also shown efficacy in treating hot flashes and improving sleep quality with possibly fewer side effects than regular gabapentin.
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Affiliation(s)
- Manisha Yadav
- Center for Specialized women's Health, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Trost LW, Serefoglu E, Gokce A, Linder BJ, Sartor AO, Hellstrom WJG. Androgen deprivation therapy impact on quality of life and cardiovascular health, monitoring therapeutic replacement. J Sex Med 2013; 10 Suppl 1:84-101. [PMID: 23387914 DOI: 10.1111/jsm.12036] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Androgen deprivation therapy (ADT) is commonly utilized in the management of both localized and advanced adenocarcinoma of the prostate. The use of ADT is associated with several adverse events, physical changes, and development of medical comorbidities/mortality. AIM The current article reviews known adverse events associated with ADT as well as treatment options, where available. Current recommendations and guidelines are cited for ongoing monitoring of patients receiving ADT. METHODS A PubMed search of topics relating to ADT and adverse outcomes was performed, with select articles highlighted and reviewed based on level of evidence and overall contribution. MAIN OUTCOME MEASURES Reported outcomes of studies detailing adverse effects of ADT were reviewed and discussed. Where available, randomized trials and meta-analyses were reported. RESULTS ADT may result in several adverse events including decreased libido, erectile dysfunction, vasomotor symptoms, cognitive, psychological and quality of life impairments, weight gain, sarcopenia, increased adiposity, gynecomastia, reduced penile/testicular size, hair changes, periodontal disease, osteoporosis, increased fracture risk, diabetes and insulin resistance, hyperlipidemia, and anemia. The definitive impact of ADT on lipid profiles, cardiovascular morbidity/mortality, and all-cause mortality is currently unknown with available data. Treatment options to reduce ADT-related adverse events include changing to an intermittent treatment schedule, biophysical therapy, counseling, and pharmacotherapy. CONCLUSIONS Patients treated with ADT are at increased risk of several adverse events and should be routinely monitored for the development of potentially significant morbidity/mortality. Where appropriate, physicians should reduce known risk factors and counsel patients as to known risks and benefits of therapy.
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Fisher WI, Johnson AK, Elkins GR, Otte JL, Burns DS, Yu M, Carpenter JS. Risk factors, pathophysiology, and treatment of hot flashes in cancer. CA Cancer J Clin 2013; 63:167-92. [PMID: 23355109 PMCID: PMC3640615 DOI: 10.3322/caac.21171] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Hot flashes are prevalent and severe symptoms that can interfere with mood, sleep, and quality of life for women and men with cancer. The purpose of this article is to review existing literature on the risk factors, pathophysiology, and treatment of hot flashes in individuals with cancer. Electronic searches were conducted to identify relevant English-language literature published through June 15, 2012. Results indicated that risk factors for hot flashes in cancer include patient-related factors (eg, age, race/ethnicity, educational level, smoking history, cardiovascular risk including body mass index, and genetics) and disease-related factors (eg, cancer diagnosis and dose/type of treatment). In addition, although the pathophysiology of hot flashes has remained elusive, these symptoms are likely attributable to disruptions in thermoregulation and neurochemicals. Therapies that have been offered or tested fall into 4 broad categories: pharmacological, nutraceutical, surgical, and complementary/behavioral strategies. The evidence base for this broad range of therapies varies, with some treatments not yet having been fully tested or showing equivocal results. The evidence base surrounding all therapies is evaluated to enhance hot flash treatment decision-making by clinicians and patients.
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Affiliation(s)
- William I Fisher
- Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA
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32
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Allameh Z, Rouholamin S, Valaie S. Comparison of Gabapentin with Estrogen for treatment of hot flashes in post-menopausal women. J Res Pharm Pract 2013; 2:64-9. [PMID: 24991606 PMCID: PMC4076904 DOI: 10.4103/2279-042x.117392] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Various non-hormonal agents have been used for the treatment of hot flashes in women with menopause. Some studies have reported that gabapentin appears to be an effective and well-tolerated treatment modality. The aim of this study was to evaluate whether the treatment with gabapentin is effective in reducing hot flash frequency and severity and also to compare gabapentin 100 mg/day, 300 mg/day and conjugated estrogen in this regards. METHODS In this comparative clinical trial, 100 post-menopausal women attending outpatient clinics of Isfahan University hospitals were included from April 2008 to February 2009. Participants randomly received gabapentin 300 mg/day, gabapentin 100 mg/day, or conjugated estrogen 0.625 mg/day for 12 weeks. Frequency and severity of hot flashes and adverse effects were compared among the three groups. FINDINGS From all, 16 participants dropped out. There were no significant differences among the groups before intervention in terms of age, body mass index and baseline hot flash frequency and severity. Hot flash diaries were used to record the frequency and severity of hot flashes. After the treatment period, there was a significant decrease in both severity and frequency of hot flashes in all three groups. Post-hoc analyses showed that the frequency and severity of hot flashes were significantly lower in those who received gabapentin 300 mg/day or estrogen 0.625 mg/day compared to those who received gabapentin 100 mg/day. There was not statistically significant difference between those who received gabapentin 300 mg/day and those who received estrogen. Very few adverse effects, mostly gastrointestinal discomfort were observed in both gabapentin groups (8%). CONCLUSION Gabapentin 300 mg/day could be useful to relieve hot flashes in women for whom hormone therapy is not suitable or when hot flashes do not respond to other therapies. Further researches are needed to determine the efficacy of gabapentin use for longer periods or at higher doses.
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Affiliation(s)
- Zahra Allameh
- Department of Obstetrics and Gynecology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Safoura Rouholamin
- Department of Obstetrics and Gynecology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sonia Valaie
- Department of Obstetrics and Gynecology, Isfahan University of Medical Sciences, Isfahan, Iran
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Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Support Care Cancer 2013; 21:1461-74. [DOI: 10.1007/s00520-013-1732-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Accepted: 01/28/2013] [Indexed: 11/26/2022]
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Abstract
Hot flashes are very common in women in menopause and can have a detrimental effect on quality of life. Hormone therapy (estrogen with or without progestin) remains the gold standard treatment for hot flashes, but concerns for the risk of hormone therapy have resulted in its decline and a demand for nonhormonal treatments with demonstrated efficacy for hot flashes. Several nonhormonal therapies have been tested in randomized placebo-controlled trials including nonpharmacologic approaches and pharmacologic nonhormonal agents. Among them, two classes of nonhormonal medications have been demonstrated to effectively alleviate hot flashes: γ-aminobutyric acid (GABA) analogs and selective serotonin reuptake inhibitors (SSRIs). This article discusses the superior efficacy of the newer nonhormonal prescriptions for the treatment of hot flashes when compared with estrogen replacement therapy, and provides some recommendations regarding use of them in peri- and postmenopausal women.
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Affiliation(s)
- Atsushi Imai
- Department of Obstetrics and Gynecology, Matsunami General Hospital, Gifu, Japan.
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35
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Steady-state pharmacokinetics of gabapentin after administration of a novel gastroretentive extended-release formulation in postmenopausal women with vasomotor symptoms. Clin Drug Investig 2012; 32:593-601. [PMID: 22775354 DOI: 10.1007/bf03261914] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND AND OBJECTIVE Approximately 75% of postmenopausal women experience vasomotor symptoms (hot flashes). Currently, hormone replacement therapy is the only approved treatment for hot flashes. However, its use has been associated with an increased risk of invasive breast cancer, coronary heart disease, stroke and venous thromboembolic disease. Gabapentin has also been demonstrated to be efficacious in the treatment of vasomotor symptoms in postmenopausal women when administered three times a day. A gastroretentive extended-release formulation of gabapentin (gabapentin-ER) has recently been demonstrated to be efficacious in the treatment of postmenopausal hot flashes. The objective of this paper is to report the steady-state pharmacokinetics and safety of gabapentin with different dosing regimens of gabapentin-ER in postmenopausal women with hot flashes. METHODS This was a multicentre, randomized, double-blind, dose-escalating, placebo-controlled, parallel group study in 124 postmenopausal women experiencing ≥7 moderate to severe hot flashes per day. The study consisted of two 5-week treatment periods, with each one preceded by a 1-week titration to the assigned dose. Groups A, B and C received gabapentin-ER 600 mg evening (pm), 600 mg morning (am)/600 mg pm and 1200 mg pm in the first period, and then 600 mg am/1200 mg pm, 600 mg am/1800 mg pm and 1200 mg am/1800 mg pm in the second period, respectively. The tablets were taken after a non-specified meal. Pharmacokinetic sampling was conducted over a 24-hour period at the end of each study period. Plasma samples were analysed by a validated liquid chromatography tandem mass spectrometry method. Non-compartmental pharmacokinetic analysis was performed on the concentration-time data to determine area under the plasma concentration versus time curve from time zero to 24 hours (AUC(24)). Maximum (C(max)), minimum (C(min)) and average (C(avg)) drug concentration and time to reach C(max) (t(max)) were determined by inspection of the data. Tolerability was evaluated by physical examination, clinical laboratory measurements and adverse events monitoring. RESULTS Gabapentin exposure at steady state, as measured by AUC(24), increased with doses from 600 mg/day to 3000 mg/day, although there was a slight decrease in gabapentin's relative bioavailability with increasing dose compared with the 600 mg dose. The relative bioavailability compared with the 600 mg dose was 86-88% for the 1200 mg/day doses, 75% for the 1800 mg/day dose, 84% for the 2400 mg/day dose, and 73% for the 3000 mg/day dose. C(max) generally increased with increasing dose as did C(min) and C(avg) for the various treatments in a manner that was consistent with the dosing regimen. The values of t(max) were not different between the various doses, with the median t(max) values relative to the most recent dose ranging from 6 to 8 hours for all dose levels. Gabapentin-ER was generally well tolerated at all doses studied. The most common AEs were headache, dizziness and somnolence, with most being mild in intensity. Seven patients withdrew from the study due to AEs. CONCLUSION The pharmacokinetic profile of gabapentin-ER may allow for once- or twice-daily dosing while maintaining bioavailability and thus efficacy. Gabapentin-ER was well tolerated. CLINICAL TRIAL REGISTRATION Registered as ClinicalTrials.gov Identifier: NCT00511953.
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Abstract
The impact of oncologic treatments on fertility and menopausal symptoms is often significant for patients with cancer. Surgery, radiation, and chemotherapy can all damage the reproductive organs or the hypothalamic pituitary axis that controls them, impairing fertility and causing hormonally mediated symptoms such as hot flashes. Understanding these risks and strategies to mitigate them may substantially improve cancer survivorship care. For both female and male patients who desire a future biologic child, there are a variety of fertility preservation techniques that should be considered. For cancer survivors who experience menopausal symptoms, lifestyle changes may be beneficial, and hormonal and nonhormonal pharmacologic agents are well proven to reduce symptom burden.
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Affiliation(s)
- Kathryn J. Ruddy
- All authors: Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA
| | - Ann H. Partridge
- All authors: Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA
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37
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Cowles VE, Gordi T, Hou SYE. Steady-State Pharmacokinetics of Gabapentin after Administration of a Novel Gastroretentive Extended-Release Formulation in Postmenopausal Women with Vasomotor Symptoms. Clin Drug Investig 2012. [DOI: 10.2165/11634520-000000000-00000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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39
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Morrow PKH, Mattair DN, Hortobagyi GN. Hot flashes: a review of pathophysiology and treatment modalities. Oncologist 2011; 16:1658-64. [PMID: 22042786 DOI: 10.1634/theoncologist.2011-0174] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
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.
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Affiliation(s)
- Phuong Khanh H Morrow
- Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
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40
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Loibl S, Lintermans A, Dieudonné A, Neven P. Management of menopausal symptoms in breast cancer patients. Maturitas 2011; 68:148-54. [DOI: 10.1016/j.maturitas.2010.11.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2010] [Revised: 11/08/2010] [Accepted: 11/09/2010] [Indexed: 10/18/2022]
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Sideras K, Loprinzi CL. Nonhormonal management of hot flashes for women on risk reduction therapy. J Natl Compr Canc Netw 2010; 8:1171-9. [PMID: 20971841 PMCID: PMC3922061 DOI: 10.6004/jnccn.2010.0086] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
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.
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Desmarais JE, Looper KJ. Managing menopausal symptoms and depression in tamoxifen users: implications of drug and medicinal interactions. Maturitas 2010; 67:296-308. [PMID: 20880642 DOI: 10.1016/j.maturitas.2010.08.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Revised: 08/10/2010] [Accepted: 08/10/2010] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Tamoxifen, a medication used in the treatment of breast cancer, often induces menopausal symptoms. Certain medications and natural supplements taken or prescribed to alleviate tamoxifen-induced hot flashes and depressive states in women with breast cancer interact with tamoxifen. This paper reviews potentially problematic interactions and offers treatment recommendations. METHODS Medline (1950-June 1, 2010), Embase Classic+Embase (1947-June 1, 2010) and PsycINFO (1967-June 1, 2010) were searched through Ovid. The word "tamoxifen" was searched with "depression" and then with "menopaus*" and "symptoms", with "treatment" as a limit. "Tamoxifen" was later searched with the MeSH terms "drug interaction" or "drug incompatibility". RESULTS Venlafaxine is efficacious for the treatment of hot flashes and depression and safe to use in combination with tamoxifen. Gabapentin is also efficacious in treating tamoxifen-induced hot flashes and, since it does not interact with cytochrome P450 system, is likely safe to use in patients using tamoxifen. Desvenlafaxine and pregabalin may be alternatives to venlafaxine and gabapentin, respectively, although desvenlafaxine has not yet been studied in this population. Paroxetine, fluoxetine and bupropion are strong CYP2D6 inhibitors which should be avoided in tamoxifen users. Fluvoxamine and nefazodone both inhibit CYP3A, which could potentially affect the metabolism of tamoxifen. Clonidine can be an alternative agent but may carry significant side effects. Evidence of medicinal products for the treatment of tamoxifen-induced hot flashes is equivocal at best. CONCLUSIONS Clinicians should remain cautious about using strong inhibitors and/or inducers of cytochrome 2D6 and 3A4 concomitantly with tamoxifen. Use of natural menopausal supplements and diets rich in isoflavones should not be encouraged in tamoxifen users until more data is available. There are however safe treatments for hot flashes and depression in tamoxifen users.
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Affiliation(s)
- Julie Eve Desmarais
- Allan Memorial Institute, McGill University Health Centre, Montreal, Quebec, Canada.
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44
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Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes. Menopause 2010; 17:908-16. [PMID: 20581724 DOI: 10.1097/gme.0b013e3181dbee1b] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Zalewski MA, Beikman S, Ferrari S, Slavish K, Rosenzweig M. Breast Cancer Follow-Up: Strategies for Successful Collaboration between Cancer Care Specialists and Primary Care Providers. J Nurse Pract 2010. [DOI: 10.1016/j.nurpra.2010.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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47
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Carroll DG, Kelley KW. Use of Antidepressants for Management of Hot Flashes. Pharmacotherapy 2009; 29:1357-74. [DOI: 10.1592/phco.29.11.1357] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Efficacy of nonestrogenic hot flash therapies among women stratified by breast cancer history and tamoxifen use: a pooled analysis. Menopause 2009; 16:477-83. [PMID: 19188850 DOI: 10.1097/gme.0b013e31818c91ca] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Various nonestrogenic therapies have been found to be effective in mitigating hot flashes, but it has been unclear whether the efficacy varies by whether women have had breast cancer and/or were taking tamoxifen. METHODS This study used data from Mayo Clinic/North Central Cancer Treatment Group clinical trials that evaluated the efficacy of any nonestrogenic agent for hot flashes and had information on breast cancer history or tamoxifen use. Statistically significant changes from the fourth treatment week versus the baseline week, using individual patient data, were assessed using Student's t test. RESULTS A total of 1,396 women from 20 hot flash studies were eligible for analysis. Overall, women without breast cancer had a similar percentage of baseline hot flash score at week 4, as did those with breast cancer (53% vs 50%, P = 0.92). Women who were not taking tamoxifen had a significantly lower percentage of hot flash score at week 4 as compared with those who used tamoxifen (54% vs 61%, P = 0.01). However, this was due to a higher reduction in hot flash scores in the placebo arms among women not receiving tamoxifen; the percentage reduction in hot flash scores at week 4 from baseline in the active therapy arms of the randomized placebo-controlled trials (ie, excluding placebo arms) was similar among the tamoxifen users and nonusers (difference in mean percentage reduction, 5.7; 95% CI, -1.76 to 13.16). CONCLUSIONS Some nonestrogenic therapies seem to be useful for reducing hot flashes, irrespective of the etiology of hot flashes.
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Abstract
Non-estrogenic alternatives for the treatment of climacteric symptoms have their origin lost in history. Recent clinical trial data have shown that lifestyle and diet adjustment have some effect in improving both hot flushes and mood. Over-the-counter phytotherapeutic extracts are very popular and women often try a variety of products before resorting to traditional medicine. Preparations containing isoflavones in variable doses, such as soy extract and red clover, or extracts from evening primrose, Cimifuga racemosa, ginseng and black cohosh are often used for treating the climacteric syndrome. The scientific support for their efficacy certainly does not equal their popularity. The most tested pharmacological alternatives to estrogens are serotonin reuptake inhibitors (SSRIs). All available SSRIs have undergone trials for the relief of hot flushes. In spite of the difference between the compounds in both half-life and engagement of serotonin receptors, they appear to have very similar effectiveness in reducing hot flushes. At their best, SSRIs reduce hot flushes by 50-60%, compared with 80% for estrogen, and their effect appears only in the short term. SSRIs have mood-improving effects that appear to be independent of the effect on hot flushes. When used for the treatment of the climacteric syndrome, SSRIs do not adversely affect libido. Dependence is a major concern in women when offered this type of treatment, but does not appear to be a problem with this class of drugs. Withdrawal symptoms have never been reported in trials for hot flushes but are known to occur when SSRIs are used in the long term. In order to avoid these symptoms, the dose should be tapered slowly. Gabapentin, a drug used for the treatment of neuropathic pain and epilepsy, has shown that, in high doses, it has an efficacy similar to that of estrogen; however, this needs further confirmation.
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Affiliation(s)
- P Albertazzi
- Contraception and Reproductive Health Services, Central Abacus, Liverpool, UK
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50
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Abstract
BACKGROUND Vasomotor symptoms are the most common complaints for which menopausal women seek medical care. Eighty per cent of all menopausal women will have hot flushes and night sweats, and of these 9% will have severe symptoms impacting their quality of life. Ideally, treatment should target the group most severely afflicted, and options for treatment should be tailored to each woman, since, for most women, vasomotor symptoms spontaneously resolve in 3 - 5 years. Recommendation at this time is for the shortest duration of therapy, which means that episodic review of therapy is indicated. OBJECTIVE To review the latest literature investigating therapies for vasomotor symptoms and to discuss their effectiveness with emphasis on placebo-controlled, randomized clinical trials. METHODS A literature search in PubMed for 'vasomotor symptoms', 'menopause symptoms', 'hot flushes', 'hot flashes' and 'night sweats' from 2003 to the present was performed. CONCLUSIONS Estrogen remains the gold standard for treating vasomotor symptoms. As investigations into the physiology of hot flushes continue, centrally active drugs (selective serotonin or norepinephrine-serotonin reuptake inhibitors and gabapentin) have increased in use. The benefit from dietary herbal supplements is still inconclusive; however, recent studies have shown some mild response to soy and black cohosh.
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Affiliation(s)
- Wen Shen
- Johns Hopkins University School of Medicine, Division of Gynecology, 600 North Wolfe Street, Phipps 249, Baltimore, MD 21287, USA .
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