MASCC/ESMO Antiemetic Guideline 2013

(1)

MASCC/ESMO Antiemetic Guideline 2013

Multinational Association

of Supportive Care in Cancer

Organizing and Overall Meeting Chairs:

Richard J. Gralla, MD Fausto Roila, MD Maurizio Tonato, MD

(2)

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- alex.molasiotis@polyu.edu.hk or

alex.molassiotis@manchester.ac.uk

(3)

•  

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 -

(4)

PARTICIPANTS IN THE PERUGIA

ANTIEMETIC GUIDELINE PROCESS: MASCC/ESMO

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

(5)

CONTINENTS AND COUNTRIES OF PARTICIPANTS

IN ANTIEMETIC GUIDELINE PROCESS: MASCC/ESMO

Asia Africa Australia/Oceania Europe North America Japan South Africa Australia Denmark Germany France Italy Switzerland United Kingdom Canada

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₊

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5HT3 = serotonin receptor antagonist DEX =

DEXAMETHASONE FOS= FOSAPREPITANT APR = APREPITANT;

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

PALO DEX

DEX

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

+

(7)

+

₊

+

DEX = DEXAMETHASONE APR= APREPITANT

SUMMARY DELAYED NAUSEA AND VOMITING

EMETIC RISK GROUP

ANTIEMETICS

High

+

Anthracycline +

Cyclophosphamide (AC)

Moderate (other than AC)

Low

Minimal

DEX* APR*

APR or none** DEX

(8)

ANTIEMETIC GUIDELINES: MASCC/ESMO

- The Process -

1)  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 to change 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.

(9)

- Committees and their Areas (1/2) -

I. Emetic classification of antineoplastic agents

II. Acute emesis: Highly emetic chemotherapy

III. Delayed emesis: Highly emetic chemotherapy

IV. Acute emesis: Moderately emetic chemotherapy

(10)

- Committees and their Areas (2/2) -

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

IXA. Radiotherapy-induced emesis

IXB. Antiemetics in children receiving chemotherapy

X. Future Considerations: Research Directions, Study

Design, Economic Considerations

(11)

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.

Keeping the Guidelines Accurate, Up-to-Date, and Valid ANTIEMETIC GUIDELINES: MASCC/ESMO

(12)

MASCC/ESMO Antiemetic Guidelines

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

(13)

MASCC/ESMO Antiemetic Guidelines

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

HIGH Cisplatin Mechlorethamine Streptozocin Cyclophosphamide > 1500 mg/m2 Carmustine Dacarbazine MODERATE Oxaliplatin Cytarabine > 1000 mg/m2 Carboplatin Ifosfamide Cyclophosphamide < 1500 mg/m2 Azacitidine Alemtuzumab Doxorubicin Daunorubicin Epirubicin Idarubicin Irinotecan Bendamustine Clofarabine

(14)

MASCC/ESMO Antiemetic Guidelines

Committee I (3/5): Emetic Risk Groups – Single IV Agents

LOW Paclitaxel Docetaxel Mitoxantrone Topotecan Etoposide Pemetrexed Methotrexate

Doxorubicin HCL liposome injection Temsirolimus Ixabepilone Mitomycin Gemcitabine Cytarabine < 1000 mg/m2 5-Fluorouracil Bortezomib Cetuximab Trastuzumab Catumaxumab Panitumumab Temsirolimus

(15)

MASCC/ESMO Antiemetic Guidelines

Committee I (4/5): Emetic Risk Groups – Single IV Agents

MINIMAL Bleomycin Busulfan Cladribine Fludarabine Vinblastine Vincristine Vinorelbine Bevacizumab 2-Chlorodeoxyadenosine

(16)

MASCC/ESMO Antiemetic Guidelines 2011

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

HIGH Hexamethylmelamine _Procarbazine

MODERATE Cyclophosphamide _Temozolomide Vinorelbine _Imatinib

LOW Capecitabine Tegafur Uracil Etoposide Sunitinib Fludarabine Everolimus Lapatinib Lenalidomide Thalidomide MINIMAL Chlorambucil Hydroxyurea Melphalan Methotrexate 6-Thioguanine Gefitinib Sorafenib Erlotinib L-Phenylalanine mustard

(17)

COMMITTEE II:

Guideline for the Prevention of Acute Nausea and Vomiting

Following Chemotherapy of High Emetic Risk:

To prevent acute nausea and vomiting following chemotherapy of high emetic risk, a three-drug regimen including single doses

of a 5-HT₃ receptor antagonist, dexamethasone, and aprepitant (or fosaprepitant) given before chemotherapy is recommended.

Level of confidence : High

Level of consensus: High

(18)

COMMITTEE III:

Guideline for the Prevention of Delayed Nausea and Vomiting

Following Chemotherapy of High Emetic Risk:

In patients receiving cisplatin treated with a combination of

aprepitant (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 confidence: High

Level of consensus: Moderate

(19)

COMMITTEE IV (1/3):

Guideline for the Prevention of Acute Nausea and Vomiting

Following 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.

Level of confidence:

High

Level of consensus: High

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

(20)

COMMITTEE IV (2/3):

Guideline for the Prevention of Acute Nausea and Vomiting

Following Chemotherapy of Moderate Emetic Risk:

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: moderate

Level of consensus: moderate

(21)

COMMITTEE IV (3/3):

Guideline for the Prevention of Acute Nausea and Vomiting

Following Chemotherapy of Moderate Emetic Risk:

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

Level of consensus: High

(22)

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AGENT ROUTE ANTIEMETICS

Ondansetron IV 8 mg or 0.15 mg/Kg Oral 16 mg* Granisetron IV 1 mg or 0.01 mg/Kg Oral 2 mg (or 1 mg**) Dolasetron Oral 100 mg*** Tropisetron IV 5 mg Oral 5 mg Palonosetron IV 0.25 mg Oral 0.5 mg

Recommended Doses of Serotonin Receptor

(5-HT

₃

) Antagonists for Acute Emesis

* Randomized studies have tested the 8 mg twice daily schedule ** The 1 mg dose preferred by some panelists

(23)

**Recommended Corticosteroid* (dexamethasone) Dosing**

DEXAMETHASONE Dose and Schedule

High Risk

- Acute Emesis (12 mg when used with aprepitant or 20 mg once

fosaprepitant)**

- Delayed Emesis (8 mg once daily when used with aprepitant 8 mg bid for 3 - 4 days 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

(24)

Recommended NK

₁

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 Emesis

Aprepitant 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 adminisered 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].

(25)

COMMITTEE V (1/3):

Guideline for the Prevention of Delayed Nausea and Vomiting

Following Chemotherapy of Moderate Emetic Risk:

Patients who receive moderately emetic chemotherapy known to be associated with a significant incidence of delayed nausea and

vomiting should receive antiemetic prophylaxis for delayed emesis.

Level of confidence: High

Level of consensus: High

(26)

COMMITTEE V (2/3):

Guideline for the Prevention of Delayed Nausea and Vomiting

Following Chemotherapy of Moderate Emetic Risk:

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

(27)

Guideline for the Prevention of Delayed Nausea and Vomiting

Following Chemotherapy of Moderate Emetic Risk:

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

Level of consensus: Moderate

(28)

COMMITTEE VI (1/3):

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

Level of consensus: Moderate

(29)

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.

Level of confidence: No confidence possible

Level of consensus: High

*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.

(30)

COMMITTEE VI (3/3):

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.

Level of confidence: No confidence possible

Level of consensus: High

*While unusual at this emetic level, if a patient experiences emesis it is advised that with subsequent

(31)

COMMITTEE VII:

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

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.

(32)

COMMITTEE VIII

(1/2):

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

(33)

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: High

Level 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: Moderate

Level of consensus: Moderate

(34)

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

LOW Cranium, 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

(35)

COMMITTEE IXA (2/5):

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)

(36)

COMMITTEE IXA (3/5):

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)

(37)

COMMITTEE IXA (4/5):

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-HT₃receptor antagonist.

Level of confidence: Moderate

(Low for rescue)

(38)

COMMITTEE IX (5/5):

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

Level of consensus: High

(39)

COMMITTEE IXB (1/3)

- Antiemetics in children -

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

Level of consensus: High

(40)

COMMITTEE IXB (2/3)

- 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.

(41)

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.