Profilassi dell'emesi. Fabio Arcidiacono, Terni

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1 Profilassi dell'emesi Fabio Arcidiacono, Terni

2 EMESI RADIOINDOTTA DIMENSIONE DEL PROBLEMA Sicuramente meno frequente e meno severa rispetto a quella indotta da chemioterapia e, per questo, forse sottovalutata Comunque da controllare adeguatamente perché può richiedere interruzione RT RADICALE ADIUVANTE SALVATAGGIO PALLIATIVA compromissione outcome peggioramento QoL

3 FISIOPATOLOGIA DELL EMESI Riflesso del Vomito CTZ CORTECCIA CEREBRALE Farmaci Oppiacei Anestetici Glicosidi cardiaci Emesi anticipatoria CENTRO VESTIBOLARE Chemioterapia EMESI cinetosi malattie Anomalie metaboliche dell orecchio Uremia interno Chetoacidosi RECETTORI PERIFERICI Ipossia (vagali e splancnici) Ingestione di tossine Chemioterapia Radioterapia

4 Mechanisms of Radio-Chemotherapy- Induced Nausea and Vomiting Radiotherapy Chemotherapy Central Brainstem NK 1 receptors Substance P Dorsal vagal complex Area postrema Enterochromaffin cell Peripheral Serotonin release Vagal afferent 5-HT 3 receptors

5 RISCHIO DI EMESI RADIOINDOTTA FATTORI CORRELATI AL PAZIENTE FATTORI CORRELATI AL TRATTAMENTO

6 Risk Stratification PT related RT related Age Sex Alcohol consumption Previous nausea & vomiting Anxiety Site of irradiation Dosing Fractionation Irradiated volume Technique

7 Emetogenic risk profile of patients Feyer,2002

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9 Risk stratification in RINV Feyer,2002

10 EMESI RADIOINDOTTA 3 studi osservazionali

11 aranzano et al.

12 Maranzano et al.

13 caratteristiche RT-relate caratteristiche PZ-relate

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15 caratteristiche RT-relate Age caratteristiche PZ-relate ask for additional treatment 23% of patients

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17 Fattori associati ad emesi TERAPIE PRECEDENTI E CONCOMITANTI SEDE RT VOLUME RT

18 tempo mediano 1 episodio vomito: 3 gg 17% pz ha ricevuto farmaci antiemetici 12% in prevenzione 5% al sintomo sottovalutazione emesi radioindotta

19 Risk Stratification PT related RT related Younger Age Upper abdomen Field size >400 cm 2 Previous chemotherapy Concomitant Chemotherapy

20 Strategie per ridurre l emesi radioindotta Prevenzione PRIMARIA Prevenzione SECONDARIA

21 PREVENZIONE PRIMARIA Piano di trattamento 3D - IMRT Impiego di schermi Valutazione DVH ridurre volume di irradiazione di OAR emesi-correlati

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23 DVH: valori predittivi emesi radioindotta

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25 Localizzazione vestiboli Assiale Sagittale

26 PREVENZIONE SECONDARIA farmaci antiemetici Profilassi Terapia alla comparsa del sintomo

27 FARMACI ANTIEMETICI Farmaci antiemetici Meccanismo d azione Antiserotoninergici blocco del recettore 5-HT3 Ondansetron Granisetron Dolasetron Tropisetron Palonosetron Antidopaminergici blocco recettore dopaminergico Metoclopramide Prometazina Tietilperazina Procloperazina Corticosteroidi sconosciuto Desametasone Metilprednisolone Anti NK1 antagonista selettivo recettori neurochinina 1 Aprepitant Fosaprepitant

28 Trials R pre 5HT3 - RA

29 pochi pz efficacia antiemetica limitata (RC 50% pz) NO differenze tra presidi farmacologici

30 Trials R profilassi 5HT3-RA

31 RT UPPER ABDOMINAL M MCP C P

32 RT UPPER ABDOMINAL 5 HT 3 RA superiore a PLACEBO M MCP C P 5 HT 3 RA superiore a METOCLOPRAMIDE 5 HT 3 RA + DESA superiore 5 HT 3 RA alone 5 HT 3 RA PROFILASSI superiore SINTOMO

33 TBI & HALF BODY IRRADIATION

34 TBI & HALF BODY IRRADIATION 5 HT3 RA superiore a placebo e antiemetici convenzionali 5 HT3 RA + CORTICOSTEROIDI superiore a corticosteroidi alone Granisetron e Ondansetron equivalenti

35 profilassi 5HT3 RA+ / - corticosteroidi

36 RT addome superiore

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38 profilassi corticosteroidi

39 RT ADDOME SUPERIORE 1 SETTIMANA RT DESAMETASONE 2mg x3/die PLACEBO PROFILASSI COMPLETA

40 profilassi NK1 - RA

41 5 HT-3 RA + NK1 RA > 5HT-3 RA alone

42 profilassi RT + CT concomitante

43 GAND emesis study palonosetron dexamethasone fosaprepitant vs palonosetron dexamethasone placebo Riduzione significativa di emesi nelle 5 settimane di RT - CT

44 durata profilassi

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46 PROFILASSI vs SINTOMO

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48 tp non farmacologica

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50 J Res Med Sci May; 19(5): Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of green tea in preventing acute gastrointestinal complications due to radiotherapy Hamid Emami, FarzanehNikoobin, MahnazRoayaei, and Hamid Reza Ziya Results: significant difference in frequency of reported diarrhea between no significant difference in frequency of vomiting Conclusion: Green tea could be effective in decreasing the frequency and severity of radiotherapy induced diarrhea.

51 aderenza Linee Guida

52 2013

53 Bassa consapevolezza Linee Guida 2013 Accordo su rischio minimo e alto Discordanza su rischio basso e moderato Profilassi sottoutilizzata nel rischio moderato

54 ANTIEMETIC GUIDELINES: MASCC/ESMO Radiotherapy-induced nausea and vomiting: MASCC/ESMO antiemetic guideline for radiotherapy - update 2015 Christina H. Ruhlmann, Franziska Jahn, Karin Jordan, Kristopher Dennis, Ernesto Maranzano, Alexander Molassiotis, Fausto Roila, Petra Feyer Submitted to J Supp Care Cancer

55 ANTIEMETIC GUIDELINES: MASCC/ESMO Committee VII (1/5): Levels of Emetic Risk with Radiation Therapy HIGH RISK LEVEL* AREA OF TREATMENT Total body irradiation MODERATE Upper abdomen, craniospinal LOW Cranium, head & neck, thorax region, pelvis MINIMAL Extremities, breast * in concomitant radiochemotherapy the antiemetic prophylaxis is according to the chemotherapy-related antiemetic guidelines of the corresponding risk category, unless the risk of emesis is higher with radiotherapy than chemotherapy

56 ANTIEMETIC GUIDELINES: MASCC/ESMO Prevention of nausea and vomiting in patients receiving highly emetic radiation therapy: Total body irradiation Patients receiving highly emetic radiation therapy should receive a 5-HT 3 receptor antagonist plus dexamethasone. MASCC level of confidence: High (for the addition of dexamethasone moderate) MASCC level of consensus: High ESMO level of evidence: II (for the addition of dexamethasone III) ESMO grade of recommendation: B (for the addition of dexamethasone C)

57 ANTIEMETIC GUIDELINES: MASCC/ESMO Prevention of nausea and vomiting in patients receiving moderately emetic radiation therapy: Upper abdomen, craniospinal Patients receiving moderately emetic radiation therapy should receive a 5-HT 3 receptor antagonist and optional short course dexamethasone. MASCC level of confidence: High (for the addition of dexamethasone moderate) MASCC level of consensus: High ESMO level of evidence: II ESMO grade of recommendation: A (for the addition of dexamethasone B)

58 ANTIEMETIC GUIDELINES: MASCC/ESMO Prevention of nausea and vomiting in patients receiving low emetic radiation therapy: Cranium, head & neck, thorax region, pelvis Patients receiving radiation therapy to head & neck, thorax region, or pelvic sites should receive prophylaxis or rescue with dexamethasone, a dopamine receptor antagonist, or a 5-HT 3 receptor antagonist. Patients receiving cranial radiation therapy should receive prophylaxis or rescue with dexamethasone. MASCC level of confidence: Low MASCC level of consensus: High ESMO level of evidence: IV ESMO grade of recommendation: D

59 ANTIEMETIC GUIDELINES: MASCC/ESMO Guideline for the prevention of nausea and vomiting in patients receiving minimal emetic radiation therapy: Extremities, breast Patients receiving minimal emetic radiation therapy should receive rescue with dexamethasone, a dopamine receptor antagonist, or a 5-HT 3 receptor antagonist. MASCC level of confidence: Low MASCC level of consensus: High ESMO level of evidence: IV ESMO grade of recommendation: D