mascc/esmo antiemetic guideline 2013 multinational association of supportive care in cancer...

MASCC/ESMO ANTIEMETICGUIDELINE 2013Multinational Association of Supportive Care in Cancer

Organizing and Overall Meeting Chairs:

Richard J. Gralla, MD

Fausto Roila, MD

Maurizio Tonato, MD

Jørn Herrstedt, MD© Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.

These slides are provided to all by the Multinational Association of Supportive Care in Cancer and can be used freely provided no changes are made and the MASCC logo and

date of the information are retained.

For questions please contact:Prof. Alex Molassiotis- [email protected]

Chair, MASCC Antiemetic Study Group

mailto:[email protected]

mailto:[email protected]

• This set of guideline slides represents the latest edition of the guideline process.

• This set of panels has been endorsed by the MASCC antiemetic guideline committee.

• The guidelines are based on the Perugia Consensus Conference on Antiemetic Therapy June 2009.

• Latest update January 2013.

- A few comments on this guideline set -ANTIEMETIC GUIDELINES: MASCC/ESMO

- Consensus -- A few comments on this guideline set -

ANTIEMETIC GUIDELINES: MASCC/ESMO

PARTICIPANTS IN THE PERUGIA ANTIEMETIC GUIDELINE PROCESS

Matti Aapro, MD

Enzo Ballatori, PhD

Emilio Bria, MD

Rebecca Clark-Snow, RN, BSN, OCN

Lawrence Einhorn, MD

Birgitte Espersen, RN

Petra Feyer, MD

Richard Gralla, MD

Steven Grunberg, MD

Jørn Herrstedt, MD

Paul Hesketh, MD

Karin Jordan, MD

Mark Kris, MD

Ernesto Maranzano, MD

Alexander Molassiotis, RN, PhD

Gary Morrow, PhD

Ian Olver, MD, PhD

Bernardo Rapoport, MD

Cynthia Rittenberg, RN, MN, AOCN

Fausto Roila, MD

Mitsue Saito, MD

Maurizio Tonato, MD

David Warr, MD

Asia

Africa

Australia/Oceania

Europe

North America

Japan

South Africa

Australia

DenmarkGermanyFranceItalySwitzerlandUnited Kingdom

CanadaUnited States of America


CONTINENTS AND COUNTRIES OF PARTICIPANTS IN ANTIEMETIC GUIDELINE PROCESS

5HT3 DEX APR

5HT3 DEX APR

PALO DEX

+ +

+ +

+

5HT3 =serotonin receptor

antagonist

DEX =DEXAMETHASONE

APR = APREPITANT;FOS= FOSAPREPITANT

PALO =PALONOSETRON

SUMMARY ACUTE NAUSEA AND VOMITING

EMETIC RISK GROUP ANTIEMETICS

High

Anthracycline + Cyclophosphamide (AC)

Moderate (other than AC)

Low

Minimal No routine prophylaxis

5HT3 DEX APR or FOS

5HT3 DEX APR or FOS

PALO DEX

DEX

* NOTE: If the NK1 receptor antagonist is not available for AC chemotherapy, palonosetron is thepreferred 5-HT3 receptor antagonist.

The Antiemetic Subcommittee of The Multinational Association of Supportive Care in Cancer. - Ann Oncol 2010; www.mascc.org.

5HT3 DRA

DRA =dopamine receptor

antagonist

+ +

OR

+

+

OR

+

5HT3 DEX APR

5HT3 DEX APR

PALO DEX

DEX

+ +

+ +

+

DEX = DEXAMETHASONE APR= APREPITANT

SUMMARY DELAYED NAUSEA AND VOMITING

EMETIC RISK GROUP ANTIEMETICS

High +

Anthracycline + Cyclophosphamide (AC)

Moderate (other than AC)

Low No routine prophylaxis

Minimal No routine prophylaxis

DEX* APR*

APR or none**

DEX

The Antiemetic Subcommittee of The Multinational Association of Supportive Care in Cancer. Ann Oncol 2010; www.mascc.org

* DEX only, if FOSAPREPITANT used on Day 1

** If FOSAPREPITANT used on Day 1

http://www.mascc.org/


The Process1) Each committee worked on its area of concentration prior to the Perugia

Meeting. At Perugia, each committee chair presented the findings of that committee to the entire group, and included the suggested rating of the level of evidence / confidence of the guideline.

2) Group discussion and consensus voting then followed each presentation.

What were the criteria for consensus?

• Degree of consensus required:67% or greater agreement among the panelists was required tochange a guideline.

• Basis of evidence to change an existing guideline:Compelling evidence was required based on well-conducted trials, generally with a comparator felt to be consistent with guidelines and representing best practice. Generally at least a 10% difference was considered to be the minimum degree of benefit sufficient for change.

I. Emetic classification of antineoplastic agents

II. Acute emesis: Highly emetic chemotherapy

III. Delayed emesis: Highly emetic chemotherapy

IV. Acute emesis: Moderately emetic chemotherapy

V. Delayed emesis: Moderately emetic chemotherapy


Committees and their Areas (1/2)

VI. Emesis induced by minimal or low emetic risk chemotherapy

VII. Additional Issues: Refractory emesis, rescue antiemetic therapy, multiple-day chemotherapy, high-dose chemotherapy

VIII. Anticipatory emesis

IX. (A.) Radiotherapy-induced emesis

IX. (B.) Antiemetics in children receiving chemotherapy

X. Future Considerations: Research Directions, Study Design, Economic Considerations


Committees and their Areas (2/2)

Ongoing process to address emerging evidence in the future:

• Committees are permanent

• Each chair queries the committee every 6 months regarding

whether there is new information which may affect the guideline

• A steering committee queries the chairs for these suggestions

• If evidence appears compelling, all group members are notified

for their opinions

• If consensus is achieved, the Web-Guideline document

(MASCC) is updated.


Process for the future:Keeping the Guidelines Accurate, Up-to-Date, and Valid


Committee I (1/5): The Four Emetic Risk Groups

HIGH Risk in nearly all patients (> 90%)

MODERATE Risk in 30% to 90% of patients

LOW Risk in 10% to 30% of patients

MINIMAL Fewer than 10% at risk

Committee I (2/5): Emetic Risk Groups – Single IV Agents

HIGH

CisplatinMechlorethamineStreptozocinCyclophosphamide > 1500 mg/m2CarmustineDacarbazine

MODERATE

OxaliplatinCytarabine > 1000 mg/m2CarboplatinIfosfamideCyclophosphamide < 1500 mg/m2AzacitidineAlemtuzumab

DoxorubicinDaunorubicinEpirubicinIdarubicinIrinotecanBendamustineClofarabine



Low

PaclitaxelDocetaxelMitoxantroneTopotecanEtoposidePemetrexedMethotrexateDoxorubicin HCL liposome injectionTemsirolimusIxabepilone

MitomycinGemcitabineCytarabine < 1000 mg/m25-FluorouracilBortezomibCetuximabTrastuzumab CatumaxumabPanitumumab


MINIMAL

BleomycinBusulfanCladribineFludarabineVinblastineVincristineVinorelbineBevacizumab2-Chlorodeoxyadenosine



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

HIGHHexamethylmelamineProcarbazine

MODERATECyclophosphamideTemozolomide

VinorelbineImatinib

LOW

CapecitabineTegafur UracilEtoposideSunitinibFludarabine

EverolimusLapatinibLenalidomideThalidomide

MINIMAL

ChlorambucilHydroxyureaMelphalanMethotrexate

6-ThioguanineGefitinibSorafenibErlotinibL-Phenylalanine mustard


Guideline for the Prevention of Acute Nausea and VomitingFollowing Chemotherapy of High Emetic Risk:

To prevent acute nausea and vomiting following chemotherapyof high emetic risk, a three-drug regimen including single dosesof a 5-HT3 receptor antagonist, dexamethasone, and aprepitant(or fosaprepitant) given before chemotherapy is recommended.

Level of confidence : High

Level of consensus: High


COMMITTEE II:

Guideline for the Prevention of Delayed Nausea and VomitingFollowing Chemotherapy of High Emetic Risk:

In patients receiving cisplatin treated with a combination ofaprepitant (or fosaprepitant*), a 5-HT3 receptor antagonist and dexamethasone to prevent acute nausea and vomiting, the combination of dexamethasone and aprepitant* is suggested to prevent delayed emesis, on the basis of its superiority to dexamethasone alone.

*However, if fosaprepitant is used in Day 1, only dexamethasone is required at days 2 - 4 post-chemotherapy


Level of consensus: Moderate


COMMITTEE III:

Guideline for the Prevention of Acute Nausea and VomitingFollowing Chemotherapy of Moderate Emetic Risk:

Women receiving a combination of anthracycline plus cyclophosphamide represent a situation with a particularly great risk of nausea and vomiting. To prevent acute nausea and vomiting, a three-drug regimen including single doses of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant (or fosaprepitant), given before chemotherapy is recommended.



* NOTE: If the NK1 receptor antagonist is not available for AC chemotherapy, palonosetron is the preferred 5-HT3 receptor antagonist.


COMMITTEE IV (1/3):


In patients who receive chemotherapy of moderate emetic risk, not including a combination of anthracycline plus cyclophosphamide, palonosetron plus dexamethasone is recommended for prophylaxis of acute nausea and vomiting.

Level of confidence : ModerateLevel of consensus: Moderate


COMMITTEE IV (2/3):


The recommended dose of dexamethasone for prophylaxis of acute nausea and vomiting from chemotherapy of moderate emetic risk is 8 mg intravenously x 1.

Level of confidence : Moderate



COMMITTEE IV (3/3):

5HT3 DEX APR

5HT3 DEX APR

PALO DEX

DEX

+ +

+ +

+

AGENT ROUTE ANTIEMETICS

OndansetronIV 8 mg or 0.15 mg/Kg

Oral 16 mg*

GranisetronIV 1 mg or 0.01 mg/Kg

Oral 2 mg (or 1 mg**)

Dolasetron Oral 100 mg***

TropisetronIV 5 mg

Oral 5 mg

PalonosetronIV 0.25 mg

Oral 0.5 mg

Recommended Doses of Serotonin Receptor(5-HT3) Antagonists for Acute Emesis

* Randomized studies have tested the 8 mg twice daily schedule** The 1 mg dose preferred by some panelists *** Oral dosing recommended rather than IV due to potential QT interval prolongation

Recommended Corticosteroid* (dexamethasone) Dosing

DEXAMETHASONE Dose and Schedule

High Risk

- Acute Emesis20 mg once

(12 mg when used with aprepitant or fosaprepitant)**

- Delayed Emesis8 mg bid for 3 - 4 days

(8 mg once daily when used with aprepitant or fosaprepitant)

Moderate Risk

- Acute Emesis 8 mg once

- Delayed Emesis 8 mg daily for 2 - 3 days(many panelists give the dose as 4 mg bid)

Low Risk - Acute Emesis 4 - 8 mg once

* While corticosteroids other than dexamethasone are effective antiemetics, the dose and schedule of dexamethasone coupled with its wide availability in various dose forms established it as the guideline agent of choice

** The 12 mg dose of dexamethasone is the only one tested with aprepitant in large randomized trials

Recommended NK1 Receptor Antagonist Dosing*

APREPITANT and FOSAPREPITANT** Dose and Schedule

- Acute Emesis

Aprepitant: 125 mg orally, once on the day of chemotherapy

- or - Fosaprepitant: 150 mg IV, once on the day of

chemotherapy

- Delayed EmesisAprepitant 80 mg orally, once daily for the 2 days after chemotherapy; or none if Fosaprepitant is

used**

* As of this update, Aprepitant and Fosaprepitant are the only approved antiemetic NK1 antagonists.

** Fosaprepitant is an intravenously administered pro-drug of aprepitant. In the countries in which fosaprepitant is available, it is indicated to replace the three-day course of oral aprepitant (125 mg) only. It should be administered at a dose of 150mg IV on day 1 ONLY. If aprepitant is used on the day of chemotherapy, it should be followed on each of the next two days by oral aprepitant 80 mg daily.

[Fosaprepitant was approved on its similar pharmacokinetic profile (Lasseter et al. J Clin Pharm. 47, 834 - 840; 2007) when tested against aprepitant, not by comparative antiemetic clinical trials].

Guideline for the Prevention of Delayed Nausea and VomitingFollowing Chemotherapy of Moderate Emetic Risk:

Patients who receive moderately emetic chemotherapy knownto be associated with a significant incidence of delayed nauseaand vomiting should receive antiemetic prophylaxis for delayed emesis.




COMMITTEE V (1/3):


In patients with breast cancer receiving a combination of anthracycline plus cyclophosphamide treated with a combination of aprepitant (or fosaprepitant), a 5-HT3 receptor antagonist and dexamethasone to prevent acute nausea and vomiting, aprepitant* should be used to prevent delayed nausea and vomiting (*or none if fosaprepitant is used on day 1).

MASCC Level of confidence : Moderate

MASCC Level of consensus: Moderate


COMMITTEE V (2/3):


In patients receiving chemotherapy of moderate emetic risk (which does not include a combination of anthracycline plus cyclophosphamide) in which palonosetron is recommended, multiday oral dexamethasone treatment is the preferred treatment for the prevention of delayed nausea and vomiting.

Level of confidence : Moderate



COMMITTEE V (3/3):

Guideline for prevention of acute nausea and vomiting in patients receiving low risk emetic agents:

A single antiemetic agent such as dexamethasone, a 5-HT3 receptor antagonist or a dopamine receptor antagonist, such as metoclopramide, is suggested for prophylaxis in patients receiving agents of low emetic risk.

Level of confidence: No confidence possible



COMMITTEE VI (1/3):

Guideline for prevention of acute nausea and vomiting in patients receiving minimal risk antineoplastic agents*:

No antiemetic should be routinely administered before chemotherapy in patients without a history of nausea and vomiting.




COMMITTEE VI (2/3):

*While unusual at this emetic level, if a patient experiences emesis it is advised that with subsequent chemotherapy treatments the regimen for the next higher emetic level should be given.

Guideline for prevention of delayed nausea and vomiting in patients receiving low or minimal risk antineoplastic agents*:

No antiemetic should be administered for the prevention of delayed emesis induced by low or minimally emetic chemotherapy.




COMMITTEE VI (3/3):

*While unusual at this emetic level, if a patient experiences emesis it is advised that with subsequent chemotherapy treatments the regimen for the next higher emetic level should be given.

Guideline for patients receiving multiple-day cisplatin:Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone for acute nausea and vomiting and dexamethasone for delayed nausea and vomiting.

Level of confidence: High; Level of consensus: High

For cisplatin given on days 1-5, the addition of an NK1 receptor antagonist (aprepitant or fosaprepitant) could be considered starting no later that day 3. The optimal administration schedule for the NK1 receptor antagonist is not yet defined.

Level of confidence: Low; Level of consensus: Low


COMMITTEE VII:

No guideline was felt to be appropriate for rescue antiemesis or high-dose (i.e. transplant) chemotherapy.

5-HT3 receptor antagonists should be dosed day 1-5, except for palonosetron that should be dosed on days 1, 3 and 5 only.

NOTE:

Guidelines for prevention of anticipatory nausea and vomiting

The best approach for anticipatory emesis is the best possible control of acute and delayed emesis.

MASCC Level of confidence: High

MASCC Level of consensus: High


COMMITTEE VIII (1/2):

Guideline for the prevention of anticipatory nausea and vomiting

Behavioral therapies, in particular progressive muscle relaxation training, systematic desensitization and hypnosis, can be used to treat anticipatory nausea and vomiting.

Level of confidence: HighLevel of consensus: High

Benzodiazepines are the only drugs that reduced the occurrence of anticipatory nausea and vomiting but their efficacy tended to decrease as chemotherapy treatments continue.

Level of confidence: ModerateLevel of consensus: Moderate


COMMITTEE VIII (2/2):

Committee IXA (1/5): Levels of Emetic Risk with Radiation Therapy


RISK LEVEL* AREA OF TREATMENT

HIGH TBI, Total nodal irradiation

MODERATE Upper abdomen, UBI, HBI

LOWCranium, craniospinal,

H & N, lower thorax region, pelvis

MINIMAL Extremities, breast

TBI: total body irradiation, HBI: half body irradiation, UBI: upper body irradiation * 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

Guideline for the prevention of nausea and vomiting in Patients receiving highly emetic radiation therapy: TBI, Total nodal irradiation

Patients receiving highly emetic radiation therapy should receive a 5-HT3 receptor antagonist plus dexamethasone.

Level of confidence: High (Moderate with the addition of dexamethasone)



COMMITTEE IXA (2/5):

Guideline for the prevention of nausea and vomiting in patients receiving moderately emetic radiation therapy: Upper abdomen, HBI, UBI

Patients receiving moderately emetic radiation therapy should receive a 5-HT3 receptor antagonist and optional short course dexamethasone.

Level of confidence: High (Moderate with the addition of dexamethasone)




Guideline for the prevention of nausea and vomiting in patients receiving radiation therapy of low emetic risk: Cranium, craniospinal, H & N, lower thorax region, pelvis

Patients receiving radiation therapy of low emetic risk should receive prophylaxis or rescue with a 5-HT3 receptor antagonist.

Level of confidence: Moderate (Low for rescue)




Guideline for the prevention of nausea and vomiting in patients receiving radiation therapy of minimal emetic risk: Extremities, breast

Patients receiving radiation therapy of minimal emetic risk should receive rescue with a dopamine receptor-antagonist or a 5-HT3 receptor antagonist.

Level of confidence: Low




Guideline for the prevention of nausea and vomiting following chemotherapy of high and moderate emetic risk in children:

All pediatric patients should receive antiemetic prophylaxis with a combination of a 5-HT3 receptor antagonist and dexamethasone.

Level of confidence: Moderate



COMMITTEE IXB (1/3):Antiemetics in Children

Guideline for the prevention of delayed nausea and vomiting following chemotherapy of high and moderate emetic risk in children:

No appropriate studies are available for the prevention of delayed nausea and vomiting in children and therefore no formal recommendation is possible.

Many panelists feel that in the absence of studies, children should be treated in a manner similar to that of adults receiving chemotherapy of this risk. Doses should be adjusted appropriately for children.



Guideline for the prevention of nausea and vomiting following chemotherapy of minimal and low emetic risk in children:

No appropriate studies are available in this setting for children, and therefore no formal recommendation is possible.

Many panelists feel that in the absence of studies, children should be treated in a manner similar to that of adults receiving chemotherapy of this risk. Doses should be adjusted appropriately for children.



mascc/esmo antiemetic guideline 2013 multinational association of supportive care in cancer...

Documents

md slide

md maurizio tonato

md jrn herrstedt

md richard gralla

md fausto roila

masccesmo antiemetic

md alexander molassiotis

md enzo ballatori