Manejo práctico de los sofocos

y de las demás toxicidades del

tratamiento hormonal

Dr. José Angel García Sáenz

Effects of estrogen deprivation

Central nervous systemHot flashes

Night sweat

Vagina dryness

Urinary issuesReproductive system

Cardiovascular system

Musculo skeletal system

Hot-flases (vasomotor sympton)

Subjective sensation of sudden heat

Rendering face

Intensive sweating

Palpipations

Anxiety

Night sweats

Detrimental QOL

Baum et al. Cancer 2003BIG 1-98 Collaborative Group NEJM 2009

Smith I et al. SABCS 2017

FACE trial

Letrozol Anastrozol

Hot flushes 33% 32%

ATAC study BIG 1-98 study

Anastrozol Tamoxifen Anastrozol Tamoxifen

Hot flushes 35% 41% 33% 32%

Increased Risk of Recurrence AfterHormone Replacement Therapy in

Breast Cancer Survivors. HABITS study

Holmberg L. JNCI 2008

n= 442•Breast Cancerssurvivors (≈60% ER+ and 30% ER-unknown)*

Hormone Therapy

Symptomatic Treatment

Arms Breast cancerevents/N

5ys cumulativeevents

Hormone Tx 39/221 22%

Control 17/221 8%

33% on adjuvant tamoxifen at randomizationAIs were no allowed; acupunture was allowed

Farmacológicos

Antidepresivos

Antiepilépticos

No farmacológicos

Acupuntura

Yoga

Hipnosis

Clonidina

Meditación

T ocupacional

Act. física

Suplementos nutricionales

Dose comparisons of pharmacologic therapies

Comparisons of different pharmacologic therapies

Comparisons of non-pharmacologic and pharmacologic therapies

Phase III, Placebo-Controlled Trial of Three Doses of Citalopram for the

Treatment of Hot Flashes: NCCTG N05C9

Barton D. JCO 2010

0%

20%

40%

60%

80%

100%

Citalopram10 mg/d

Citalopram20 mg/d

Citalopram30 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.

Venlafaxine in management of hot flashes in survivors of breast cancer: a

randomized controlled trial.

Loprinizi. Lancet 2000

Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects.

Gabapentin for hot flashes in 420 womenwith breast cancer: a randomised double-

blind placebo-controlled trial

Pandya. Lancet 2005

Gabapentin is effective in the control of hot flashes in women with breast cancer at dose of 900 mg/day.

Paroxetine is an effective treatment forhot flashes: results from a prospective

randomized clinical trial.

Stearns.JCO 2005

Paroxetine is is an effective treatment for hot flashes in women with prior breast cancer. Women were less likely to discontinue low-dose paroxetine.

▪ 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 norespondedores (salvo Venlafaxina y Paroxetina).

Dose comparisons of pharmacologic therapies

Comparisons of different pharmacologic therapies

Comparisons of non-pharmacologic and pharmacologic therapies

Interventions Hot flashes QOLPatientpreference

Aditional sideeffects

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:↑dizzinessNegative mood

=

(3)

Venlafaxine 75 mg

Clondine 0.1 mg= = =

Venlafaxine: ↓appetite↑nausea↑constipation

Clonidine:↑pain↓blood pressure

=

(4)Venlafaxine 75 mg

Clondine 0.15 mgFavor 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

Dose comparisons of pharmacologic therapies

Comparisons of different pharmacologic therapies

Comparisons of non-pharmacologic and pharmacologic therapies

Lesi G. JCO 2016

n= 190Breast cancer

patients

Acupuncture + enhanced self-care

Enhanced self-care alone

Acupuncture for the treatment of Hot Flashes in women with Breast Cancer: A Prospective Multicenter Randomized

Controlled Trial (AcCliMaT)

Interventions Hot flashes QOLAditionalside effects

Time tohot-flashes improvement

(1)

Gabapentine

AcupuntureFavor Gabapentine NA

Gabapentine:↑dizziness↑fatigue↑drowsiness

Acupunture:↑bruising

=

(2)

Venlafaxine

Acupunture

= during active treatment

Acupunture with longerdurability of effect

=

Venlafaxine↑nausea↑cheadache↑dizziness

=

(1) Mao. JCO 2015 (2) Walker. JCO 2010

Pharmacologic therapies vs acupunture

Interventions Hot flashes QOLAditional side

effects

Time tohot-flashes

improvement

(1)Gabapentine

Vitamine E

Favor Gabapentine

Favor Gabapentine

Gabapentine:↑sleep quality

Favor Gabapentine

(2)Gabapentine

Hypnosis= NA NA =

(3)Pregabaline

Stellate ganglion block

Favor stellateganglion block =

TransientHorner's Sd.

=

(4) Soy or Red Clover

Placebo

=NA NA =

(1) Biglia . Climateric 2009 (2) Maclaughlan David. BMJ 2013(3) Othan. Pain Med. 2014 (4) Nelson. JAMA 2006

Other non-pharmacologic therapies

Adverse efects of non-hormonal pharmacologicalinterventions in BC survivors suffering hot flashes

Brook Hervik. Breast Cancer Res Treat 2016

HR 95% CI p

High drug doses vs low drug doses 1.67 1.31-2.13 <0.0001

Non-hormonal medication vs placebo 1.51 1.16-1.98 =0.002

Non-hormonal medication vs acupunture 1.75 1.092.75 =0.02

Sequedad vaginal

Atrofia

Adelgaz. epitelio

Relaciones dolorosas

Quemazón

ITUs

✓Evitar jabones

✓Usar hidratantes y lubricantes.

✓Fisoterapia de suelo pélvico

✓Dilatadores vaginales

✓Infiltración botox

✓Estrógenos tópicos ??

✓Laser CO2

✓Talleres de soporte

✓Venlafaxina

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

Optimize cardiovascular risk

Monitor lipid levels, blood presure and providecardiovascular monitoring and treatment

Educate on healthy lifestyle and potential cardiac riskfactors

Cognitive Impairment

Ask patients if they are experiencing cognitivedifficulties

Asses for reversible contributing factors

Refer for neurocognitive assesment and rehabilitation

▪ 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).

Conclusiones

▪ 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.