Dr. José Angel García Sáenz. Manejo práctico de los sofocos y de las demás toxicidades del tratamiento hormonal

Transcripción

1 Dr. José Angel García Sáenz Manejo práctico de los sofocos y de las demás toxicidades del tratamiento hormonal

2 Effects of estrogen deprivation Central nervous system Reproductive system Hot flashes Night sweat Vagina dryness Urinary issues Cardiovascular system Musculo skeletal system

3 Hot-flases (vasomotor sympton) Subjective sensation of sudden heat Rendering face Intensive sweating Palpipations Anxiety Night sweats Detrimental QOL

4 FACE trial Letrozol Anastrozol Hot flushes 33% 32% ATAC study BIG 1-98 study Anastrozol Tamoxifen Anastrozol Tamoxifen Hot flushes 35% 41% 33% 32% Baum et al. Cancer 2003 BIG 1-98 Collaborative Group NEJM 2009 Smith I et al. SABCS 2017

5 Increased Risk of Recurrence After Hormone Replacement Therapy in Breast Cancer Survivors. HABITS study n= 442 Breast Cancers survivors ( 60% ER+ and 30% ER-unknown)* Hormone Therapy Symptomatic Treatment Arms Breast cancer events/n 5ys cumulative events Hormone Tx 39/221 22% Control 17/221 8% 33% on adjuvant tamoxifen at randomization AIs were no allowed; acupunture was allowed Holmberg L. JNCI 2008

6 Antidepresivos Farmacológicos Antiepilépticos Clonidina No farmacológicos Acupuntura Yoga Hipnosis Meditación T ocupacional Act. física Suplementos nutricionales

7 Dose comparisons of pharmacologic therapies Comparisons of different pharmacologic therapies Comparisons of non-pharmacologic and pharmacologic therapies

8 Barton D. JCO 2010 Phase III, Placebo-Controlled Trial of Three Doses of Citalopram for the Treatment of Hot Flashes: NCCTG N05C9 100% 80% 60% 40% 20% 0% Citalopram 10 mg/d Citalopram 20 mg/d Citalopram 30 mg/d Citalopram is an effective, well-tolerated agent in managing hot flashes broader helpful effects of the agent appear to be more evident at 20 mg/d.

9 Loprinizi. Lancet 2000 Venlafaxine in management of hot flashes in survivors of breast cancer: a randomized controlled trial. Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects.

10 Pandya. Lancet 2005 Gabapentin for hot flashes in 420 women with breast cancer: a randomised doubleblind placebo-controlled trial Gabapentin is effective in the control of hot flashes in women with breast cancer at dose of 900 mg/day.

11 Stearns.JCO 2005 Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. Paroxetine is is an effective treatment for hot flashes in women with prior breast cancer. Women were less likely to discontinue low-dose paroxetine.

12 Citalopram, Venlafaxina, Gabapentina y Paroxetina son eficaces y tienen una aceptable tolerancia. El beneficio se observa a las 1-2 semanas. Valorar empezar a dosis bajas, y escalar en no respondedores (salvo Venlafaxina y Paroxetina).

13 Dose comparisons of pharmacologic therapies Comparisons of different pharmacologic therapies Comparisons of non-pharmacologic and pharmacologic therapies

14 Interventions Hot flashes QOL Patient preference Aditional side effects Time to hot flashes improvement (1) Venlafaxine 75 mg Clondine 0.1 mg = NA = Venlafaxine: appetite Favor venlafaxine (2) Venlafaxine 75 mg Gabapentine 900 mg = = Venlafaxine Venlafaxine appetite nausea constipation Gabapentine: dizziness Negative mood = (3) Venlafaxine 75 mg Clondine 0.1 mg = = = Venlafaxine: appetite nausea constipation Clonidine: pain blood pressure = (4) Venlafaxine 75 mg Clondine 0.15 mg Favor venlafaxine NA NA Venlafaxine: nausea Favor venlafaxine (1) Boekho. JCO 2011 (2) Bordeleau. JCO 2010 (3) Bujis. Breast Cancer Res Treat 2009 (4) Loibl. Ann Oncol 2007

15 Dose comparisons of pharmacologic therapies Comparisons of different pharmacologic therapies Comparisons of non-pharmacologic and pharmacologic therapies

16 Acupuncture for the treatment of Hot Flashes in women with Breast Cancer: A Prospective Multicenter Randomized Controlled Trial (AcCliMaT) n= 190 Breast cancer patients Acupuncture + enhanced self-care Enhanced self-care alone Lesi G. JCO 2016

17 Pharmacologic therapies vs acupunture Interventions Hot flashes QOL Aditional side effects Time to hot-flashes improvement (1) Gabapentine Acupunture Favor Gabapentine NA Gabapentine: dizziness fatigue drowsiness Acupunture: bruising = (2) Venlafaxine Acupunture = during active treatment Acupunture with longer durability of effect = Venlafaxine nausea cheadache dizziness = (1) Mao. JCO 2015 (2) Walker. JCO 2010

18 (1) Biglia. Climateric 2009 (2) Maclaughlan David. BMJ 2013 (3) Othan. Pain Med (4) Nelson. JAMA 2006 Other non-pharmacologic therapies (1) (2) (3) (4) Interventions Hot flashes QOL Gabapentine Vitamine E Gabapentine Hypnosis Pregabaline Stellate ganglion block Soy or Red Clover Placebo Favor Gabapentine Favor Gabapentine Aditional side effects Gabapentine: sleep quality Time to hot-flashes improvement Favor Gabapentine = NA NA = Favor stellate ganglion block = = Transient Horner's Sd. NA NA = =

19 Brook Hervik. Breast Cancer Res Treat 2016 Adverse efects of non-hormonal pharmacological interventions in BC survivors suffering hot flashes HR 95% CI p High drug doses vs low drug doses 1.67 Non-hormonal medication vs placebo 1.51 Non-hormonal medication vs acupunture < = =0.02

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21 Sequedad vaginal Atrofia Adelgaz. epitelio Relaciones dolorosas Quemazón ITUs

22 Evitar jabones Usar hidratantes y lubricantes. Fisoterapia de suelo pélvico Dilatadores vaginales Infiltración botox

23 Estrógenos tópicos?? Laser CO2 Talleres de soporte Venlafaxina

24 Bone Surveillance in BC survivors Screening for risk of osteoporosis Initiante bisphosphonate/denosumab if T-score <2.5 Reassess risk for low-risk patients annually

25 Optimize cardiovascular risk Monitor lipid levels, blood presure and provide cardiovascular monitoring and treatment Educate on healthy lifestyle and potential cardiac risk factors

26 Cognitive Impairment Ask patients if they are experiencing cognitive difficulties Asses for reversible contributing factors Refer for neurocognitive assesment and rehabilitation

27 Conclusiones Antidepresivos (ISRS) y Gabapentina: eficaces y con aceptable tolerancia. Venlafaxina es una buena opción como primera linea para los sofocos en cáncer de mama Empezar a dosis bajas, y escalar en no respondedores (salvo Venlafaxina y Paroxetina).

28 La acupuntura en pacientes que no deseen más pastillas, o en los que han fracasado los ttos farmacológicos. En resumen, hay medidas no hormonales para tratar los sofocos y sequedad vaginal, que deben ser discutidas individualmente Manejo de la sequedad vaginal, osteoporosis, riesgo cardiovascular y cognitivo.