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ANTIEMETIC GUIDELINES: MASCC/ESMO

Open Issues for CINV

Do we reliably measure that? Do we control nausea optimally? Are guidelines useful for oral therapies related

nausea and vomiting? Breakthrough and refractory nausea and

vomiting: where we are? Are we missing something regarding

anticipatory nausea and vomiting?

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AcuteNausea

AcuteVomiting

DelayedNausea

DelayedVomiting

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f Pat

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s MD/RN predictionPatient experience

Physicians and nurses from 14 oncology practices in 6 countriesPatients [N=298] 75% women; 78% Mod emetic chemo; 50% breast cancer; 18% lung cancer

PERCEPTIONS AND REALITYUnderestimation of Emesis with Chemotherapy

Grunberg S et al., Cancer 2004; 100: 2261-8

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The ‘ANCHOR’ Study: Prediction vs Observed

MD/RD prediction (N=24)

Patients’ perception (N=231)

HEC MEC

Grunberg S et al., Cancer 2004; 100: 2261-8

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Di Maio M et al, JCO 2015

Perceptions and RealityAgreement between patient and physician reporting

Subjective toxicities are at high risk of under- reorting by phisicians, even when prospectively collected within randomized trials.

ANTIEMETIC GUIDELINES: MASCC/ESMO

Di Maio M et al, JCO 2015

Perceptions and RealityAgreement between patient and physician reporting

ANTIEMETIC GUIDELINES: MASCC/ESMO

Aapro M & Grunberg S, Educational ASCO 20122016 V.1.27

BUT WHAT IS NAUSEA?

Nausea is subjective; vomiting is objective.Therefore the accurate measuremnet of nausea is more of anobstacle

For patients nausea ( if they understand the word at all) oftenmeans << feeling bad>>

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2016 V.1.28

NAUSEA AND APPETITE

Several agents that have appetite stimuing properties also haveanti- nausea properties:CorticosteroidMegestrolOlanzapineDronabinol

Nausea/anorexia may be a more valid construct thennausea/vomiting

A low dose anti-nausea agent might complement anti-vomitingagents

Modified by Grunberg S & Clark-Snow, Educational ASCO 2012

ANTIEMETIC GUIDELINES: MASCC/ESMO

The MASCC/ESMO Antiemetics Guidelines Committee has discussed the presently available published data about olanzapine, which suggest that it is an effective antiemetic agent.

Olanzapine may be considered with a 5-HT3 receptor antagonist plus dexamethasone, particularly when nausea is an issue.(NOTE: Patient sedation may be a concern for the 10 mg dose.)

MASCC Level of Confidence : Low

MASCC Level of Consensus: Low

ESMO Level of Evidence: II

ESMO Grade of Recommendation: B

COMMITTEE II (5/5):

ANTIEMETIC GUIDELINES: MASCC/ESMO

2016 V.1.210

Are guidelines useful for oral therapiesrelated nausea and vomiting?

ANTIEMETIC GUIDELINES: MASCC/ESMO

HIGHHexamethylmelamineProcarbazine

MODERATEBosutinibCeritinib Crizotinib

CyclophosphamideImatinibTemozolomide

Vinorelbine

LOW

AfatinibAxatinibCapecitabineDabrafenibDasatinibEverolimusEtoposideFludarabine

IbrutinibIdelalisibLapatinibLenalidomideOlaparibNilotinibPazopanib

PonatinibRegorafenibSunitinibTegafur UracilThalidomideVandetanibVorinostat

MINIMAL

ChlorambucilErlotinibGefitinibHydroxyureaMelphalan

MethotrexateL-Phenylalanine mustardPomalidomideRuxolitinib

Sorafenib6-ThioguanineVemurafenibVismodegib

Committee I (5/5): Emetic Risk Groups – Adults – Single Oral Agents

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ANTIEMETIC GUIDELINES: MASCC/ESMO

Caveats:

Drug-drug interactions

Polipharmacotherapies

Adherence

Duration of antiemetic prophylaxis?

Rescue with antiemetic therapies?

Same guidelines of iv emetogenic therapies?

No recommendations for single oral agents-related nausea/vomiting

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Breakthrough Nausea and Vomiting

Breakthrough CINV is defined as nausea and/or vomiting attributable to antineoplasticchemotherapy that occurs during the acute or

delayed phase despite CINV prophylaxis.

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For example

Initial Presentation

Mary T. is a 56-year-old female had a mastectomy and auxiliary lymph node dissection.

Diagnosis – T3 (more than 5 cm) N0(0/6 lymph nodes) M0; poorly differentiated invasive ductal carcinoma of right breast, ER/PR positive and HER-2/neu negative.

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Medical history….

PAST MEDICAL HISTORY: Unremarkable.

SOCIAL HISTORY: School teacher, married, mother of two grown children, non smoker, occasional drink on the weekends.

MEDICATIONS: Ranitidine 150 mg b.i.d., Lorazepam 1 mg prn

Allergies : NKA (drugs, food, environmental allergens)

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First Cycle of Chemotherapy (FEC)

The patient is prescribed FEC (Fluorouracil, Epirubicin, Cyclophosphamide) – for 3 cycles followed by Taxotere for 3 cycles.

She was given Ondansetron 8 mg and Dexamethasone 8 mg prior to her first cycle of chemotherapy.

She was given a prescription for Ondansetron 8 mg and Dexamethasone 4 mg po b.i.d. x 2 days post chemotherapy as well as Metoclopramide 10 mg po q6hprn to be taken post chemotherapy.

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Breakthrough nausea Nausea and Vomiting post Cycle 1

When she returned for cycle two she informed that she had vomited on day 2 and that she had experienced nausea for days 2-5 post chemotherapy.

She rates this nausea as a 8/10 for days 2-4 and 6/10 for day 5, olanzapine 10 mg for three days was administered without results.

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Guideline for Breakthrough Nausea and Vomiting

The available evidence for breakthrough nausea and vomiting suggests the use of 10 mg oral olanzapine, daily for 3 days.

(The mild to moderate sedation in this patient population,especially elderly patients, is a potential problem with olanzapine.)

MASCC Level of Confidence: ModerateMASCC Level of Consensus: ModerateESMO Level of Evidence: IIESMO Grade of Recommendation: B

NOTE: No guideline was felt to be appropriate for refractory nausea and vomiting.

COMMITTEE V (3/3):

ANTIEMETIC GUIDELINES: MASCC/ESMO

Olanzapine Breaktrough

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Refractory Nausea and Vomiting

Refrectory CINV is defined as nausea and/or vomitingattributable to antineoplastic chemotherapy whichoccurs during the acute or delayed phase despite

CINV prophylaxis in patients who have experiencedbrekthrough CINV in a previous chemotherapy cycle

ANTIEMETIC GUIDELINES: MASCC/ESMO

Second Cycle of Chemotherapy (FEC)

She was given Ondansetron 12 mg and Dexamethasone 12 mg prior to her second cycle of chemotherapy.

She was given a prescription for Ondansetron 8 mg po b.i.d. and Dexamethasone 4 mg po b.i.d. x 5 days post chemotherapy

ANTIEMETIC GUIDELINES: MASCC/ESMO

Refractory nausea Nausea and Vomiting post Cycle 2

When she returned for cycle three she informed that she had vomited on day 3-5 and that she had experienced nausea for days 3-7 post chemotherapy.

She rates this nausea as a 10/10 for days 3-4 and 6/10 for day 5-7

ANTIEMETIC GUIDELINES: MASCC/ESMOPractical Suggestions forrefractory nausea and vomiting

1) For patients receiving minimally, low emetogenicchemotherapy, upgrade or escalate the acute CINV prophylaxisto that recommended for chemotherapy of the next higherlevel of emetogenic risk.

2) For patients receiving moderately or highly emetogenicchemotherapy, we suggest that the 5-HT3 antagonist given for CINV prophylaxis be changed from ondansetron or granisetronto palonosetron or pass to NK1 antagonist

3) Stimulation of Nei Gaun (P6) by means of acupressure or electroacupuncture.

ANTIEMETIC GUIDELINES: MASCC/ESMO

MASCC/ESMO 2016 RECOMMENDATIONS

Refractory emesis

another 5-HT3 add benzodiazepines metopimazine NK1 antagonist

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Anticipatory nausea and vomiting

Anticipatory nausea and/or vomiting is the occurrence of nausea and/or vomiting before patients receive their chemotherapy treatment.

Challenge - Anticipatory nausea and/or vomiting occurs in 18% to 57% of chemotherapy patients.

Younger patients may be more susceptible as they generally receive more aggressive therapy and have poorer emesis control than older patients.

Adapted from: 1. Roscoe JA, et al. J Pain Symptom Manage 2000;20:113. 2. Morrow GR, et al. Support Care Cancer 1998;6:244.

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ANTIEMETIC GUIDELINES: MASCC/ESMO

Risk Factors

Kamen C et al, Eur J Pharmacol, 2014

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991 patients; perspective observational european study AN reported in 8.3-13.8% of patients Increase frequency and intensity over each cycle Key predictors of AN: pre-chemotherapy anxiety; AN and CINV

experience in previous cycle

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Prevention of Anticipatory Nausea and Vomiting

The best approach for the prevention of anticipatory nausea and vomiting is the best possible control of acute and delayed nausea and vomiting.

MASCC Level of Confidence: High

MASCC Level of Consensus: High

ESMO Level of Evidence: III

ESMO Grade of Recommendation: A

COMMITTEE VI (1/2):

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Prevention of Anticipatory Nausea and VomitingBehavioral therapies (progressive muscle relaxation training, in particular), systematic desensitization, and hypnosis may be used to treat anticipatory nausea and vomiting.

MASCC Level of Confidence: Moderate

MASCC Level of Consensus: Moderate

ESMO Level of Evidence: II

ESMO Grade of Recommendation: B

Benzodiazepines can reduce the occurrence of anticipatory nausea and vomiting.

MASCC Level of Confidence: Moderate

MASCC Level of Consensus: Moderate

ESMO Level of Evidence: II

ESMO Grade of Recommendation: A

COMMITTEE VI (2/2):

ANTIEMETIC GUIDELINES: MASCC/ESMO….and what about nausea between 5 to 21 days after chemotherapy?

2016 V.1.2

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ANTIEMETIC GUIDELINES: MASCC/ESMO

Grazie per la Vostra Attenzione

2016 V.1.2

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