© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
MASCC/ESMO Antiemetic Guideline 2011
Multinational Association
of Supportive Care in Cancer
Organizing and Overall Meeting Chairs:
Richard J. Gralla, MD
Fausto Roila, MD
Maurizio Tonato, MD
Jørn Herrstedt, MD
© 2011 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:
Rebecca Clark-Snow - rclark_snow@yahoo.com
Chair, MASCC Antiemetic Study Group
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
• 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 April 2011.
- A few comments on this guideline set -
ANTIEMETIC GUIDELINE CONSENSUS: MASCC/ESMO
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
David Warr, MD
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
United States of America
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
5HT3 DEX APR
5HT3 DEX APR
PALO DEX
DEX
+ +
+ +
+
5HT3 =
serotonin receptor
antagonist
DEX =
DEXAMETHASONE
APR =
APREPITANT
PALO =
PALONOSETRON
SUMMARY ACUTE NAUSEA AND VOMITING
EMETIC RISK GROUP ANTIEMETICS
High + +
Anthracycline +
Cyclophosphamide (AC) + +
Moderate (other than AC) +
Low or or
Minimal No routine prophylaxis
5HT3 DEX APR
5HT3 DEX APR
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
DEX
The Antiemetic Subcommittee of The Multinational Association of Supportive Care in Cancer.
Ann Oncol 2010; www.mascc.org.
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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.
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
ANTIEMETIC GUIDELINES: MASCC/ESMO
- 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
V. Delayed emesis: Moderately emetic chemotherapy
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
ANTIEMETIC GUIDELINES: MASCC/ESMO
- 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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
Process for the future:
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
MASCC/ESMO Antiemetic Guidelines 2011
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
MASCC/ESMO Antiemetic Guidelines 2011
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
MASCC/ESMO Antiemetic Guidelines 2011
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
Catumaxomab
Panitumumab
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
MASCC/ESMO Antiemetic Guidelines 2011
Committee I (4/5): Emetic Risk Groups – Single IV Agents
MINIMAL
Bleomycin
Busulfan
Cladribine
Fludarabine
Vinblastine
Vincristine
Vinorelbine
Bevacizumab
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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.
Level of confidence: High
Level of consensus: Moderate
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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.
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
5HT3 DEX APR
5HT3 DEX APR
PALO DEX
DEX
+ +
+ +
+
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-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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
Recommended Corticosteroid* (dexamethasone) Dosing
DEXAMETHASONE Dose and Schedule
High Risk
- Acute Emesis
20 mg once
(12 mg when used with aprepitant or
fosaprepitant)**
- Delayed Emesis
8 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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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: 115 mg IV, once on
the day of chemotherapy
- Delayed Emesis Aprepitant 80 mg orally, once daily for the 2 days after chemotherapy
* 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 first day of oral aprepitant (125 mg) only. If
either aprepitant or fosaprepitant 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.
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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.
MASCC Level of confidence: Moderate
MASCC Level of consensus: Moderate
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
COMMITTEE V (3/3):
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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.
COMMITTEE VI (2/3):
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
chemotherapy treatments the regimen for the next higher emetic level should be given.
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
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:
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
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
COMMITTEE VIII (2/2):
© 2011 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.
COMMITTEE IXA (1/5)
- Levels of Emetic Risk with Radiation Therapy -
RISK LEVEL