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Guidelines Index
Antiemesis Table of Contents
Discussion, ReferencesAntiemesis
Practice Guidelines
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NCCN Clinical Practice Guidelines in Oncology™
Antiemesis
Version 2.2010
www.nccn.org
Version 2.2010, 04/07/2010 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Guidelines Index
Antiemesis Table of Contents
Discussion, ReferencesAntiemesis
Practice Guidelines
in Oncology – v.2.2010
®
NCCN
NCCN Antiemesis Panel Members
Steve Kirkegaard, PharmD å
Huntsman Cancer Institute at the University
of Utah
Dwight D. Kloth, PharmD, FCCP, BCOP å
Fox Chase Cancer Center
Mark G. Kris, MD †
Memorial Sloan-Kettering Cancer Center
Dean Lim, MD †
City of Hope Comprehensive Cancer Center
Michael Anne Markiewicz, PharmD å
University of Alabama at Birmingham
Comprehensive Cancer Center
Laura Boehnke Michaud, PharmD, BCOP å
The University of Texas M.D. Anderson
Cancer Center
Lida Nabati, MD £ Þ
Dana-Farber/Brigham and Women's Cancer
Center | Massachusetts General Hospital
Cancer Center
Hope S. Rugo, MD † ‡
UCSF Helen Diller Family
Comprehensive Cancer Center
Steven M. Sorscher, MD †
Siteman Cancer Center at Barnes-
Jewish Hospital and Washington
University School of Medicine
Lisa Stucky-Marshall, RN, MS, AOCN #
Robert H. Lurie Cancer Center of
Northwestern University
Barbara Todaro, PharmD å
Roswell Park Cancer Institute
Susan Urba, MD † £
University of Michigan
Comprehensive Cancer Center
‡Hematology/hematology oncology
ÞInternal medicine
†Medical Oncology
#Nurse
åPharmacology
£Supportive Care including Palliative, Pain management,
Pastoral care and Oncology social work
*Writing Committee member
*David S. Ettinger, MD/Chair †
The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins
Debra K. Armstrong, RN #
Vanderbilt-Ingram Cancer Center
Sally Barbour, PharmD, BCOP å
Duke Comprehensive Cancer Center
Michael J. Berger, PharmD, BCOP å
The Ohio State University Comprehensive
Cancer Center - James Cancer Hospital
and Solove Research Institute
Philip J. Bierman, MD † ‡
UNMC Eppley Cancer Center at The
Nebraska Medical Center
Bob Bradbury, BCPS å
H. Lee Moffitt Cancer Center & Research
Institute
Georgianna Ellis, MD †
Fred Hutchinson Cancer Research Center/
Seattle Cancer Care Alliance
*
*
Continue
Disclosure of Conflict of Interest
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Guidelines Index
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Practice Guidelines
in Oncology – v.2.2010
®
NCCN
Table of Contents
CHEMOTHERAPY INDUCED:
RADIATION-INDUCED:
ANTICIPATORY:
NCCN Antiemesis Panel Members
Summary of Guidelines Updates
Principles of Emesis Control for the Cancer Patient (AE-1)
!High Emetic Risk Intravenous Chemotherapy - Emesis Prevention (AE-2)
!Moderate Emetic Risk Intravenous Chemotherapy - Emesis Prevention (AE-3)
!Low and Minimal Emetic Risk Intravenous Chemotherapy - Emesis Prevention (AE-4)
!Oral Chemotherapy - Emesis Prevention (AE-5)
!Breakthrough Treatment for Chemotherapy Induced Nausea / Vomiting (AE-6)
!Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7)
!Emetogenic Potential of Oral Antineoplastic Agents (AE-9)
!Principles of Managing Multi-Day Emetogenic Chemotherapy Regimens (AE-A)
!Principles for Managing Breakthrough Emesis (AE-B)
!Radiation-Induced Nausea / Vomiting (AE-10)
!Anticipatory Nausea / Vomiting (AE-11)
Guidelines Index
Print the Antiemesis Guideline
These guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical
circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties
of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These
guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2010.
Clinical Trials:
NCCN Categories of Consensus:
All recommendations are Category
2A unless otherwise specified.
See
The NCCN
believes that the best management
for any cancer patient is in a clinical
trial. Participation in clinical trials is
especially encouraged.
To find clinical trials online at NCCN
member institutions, click here:
nccn.org/clinical_trials/physician.html
NCCN Categories of Consensus
For help using these
documents, please click here
Discussion
References
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Guidelines Index
Antiemesis Table of Contents
Discussion, ReferencesAntiemesis
Practice Guidelines
in Oncology – v.2.2010
®
NCCN
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
UPDATES
Summary of the major changes in the 1.2010 version of the NCCN Antiemesis Guidelines from the 4.2009 version are:
·Changed first sub-bullet to state “The risk of nausea/vomiting for persons receiving chemotherapy of high and moderate emetic risk lasts
for at least 3 days for high and 2 days for moderate after the last dose of chemotherapy.”
·Reformatted recommendations for high emetic risk intravenous chemotherapy and added the drug classes to the page.
·Removed footnote “Fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant (125 mg) 30 minutes prior to chemotherapy, on
Day 1 only of the CINV regimen as an infusion administered over 15 minutes.”
·Removed the “preferred, category 2B” designation from palonosetron. Palonosetron remains a category 2A recommendation.
·Removed footnote “In a randomized study, a larger dose of palonosetron was used without aprepitant. Saito M, Aogi K, Sekine I, et al.
Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy:
a double-blind, double-dummy, randomized, comparative phase III trial. Lancet Oncol 2009;10:115-124.”
·Reformatted recommendations for moderate emetic risk intravenous chemotherapy to be consistent with AE-2, and added the drug
classes to the page.
·Added drug classes to breakthrough treatment for chemotherapy induced nausea/vomiting.
·Added romidepsin to the list of intravenous agents with low emetic risk.
·Estramustine was added to the list of oral agents with antiemetic prophylaxis recommended.
·Pazopanib was added to the list of oral agents with antiemetic agents given only as needed (ie, PRN).
·Second bullet: “The general principle of breakthrough treatment is to give an additional agent from a different drug class. No one
treatment is better than the other for managing breakthrough emesis.” The following statement was added “Some patients may require
several agents utilizing differing mechanisms of action.”
AE-1
AE-2
AE-3
AE-6
AE-8
AE-9
AE-B
Summary of the major changes in the 2.2010 version of the NCCN Antiemesis Guidelines from the 1.2010 version are:
·The addition of the updated Discussion section.
·Changed the format for moderate emetic risk chemotherapy, by separating Day 1 emesis prevention from Days 2 and 3.
MS-1
AE-3
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Guidelines Index
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Practice Guidelines
in Oncology – v.2.2010
®
NCCN
PRINCIPLES OF EMESIS CONTROL FOR THE CANCER PATIENT
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
AE-1
·
>
and 2 days for moderate after the last dose of chemotherapy. Patients need to be protected throughout the full period of risk.
·Oral and IV antiemetic formulations have equivalent efficacy.
·Consider the toxicity of the specific antiemetic(s).
·Choice of antiemetic(s) used should be based on the emetic risk of the therapy, prior experience with antiemetics, as well as patient
factors.
·There are other potential causes of emesis in cancer patients.
These may include:
>Partial or complete bowel obstruction
>Vestibular dysfunction
>Brain metastases
>Electrolyte imbalance: hypercalcemia, hyperglycemia, hyponatremia
>Uremia
>Concomitant drug treatments including opiates
>Gastroparesis: tumor or chemotherapy (vincristine etc) induced or other causes (eg, diabetes).
>Psychophysiologic:
FAnxiety
FAnticipatory nausea/vomiting
·For use of antiemetics for nausea/vomiting that are not related to radiation and/or chemotherapy,
·For multi-drug regimens, select antiemetic therapy based on drug with the highest emetic risk.
·Consider using an H2 blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea.
Prevention of nausea/vomiting is the goal.
The risk of nausea/vomiting for persons receiving chemotherapy of high and moderate emetic risk lasts for at least 3 days for high
See NCCN Palliative Care Guidelines
See Emetogenic Potential of Intravenous
Antineoplastic Agents (AE-7)
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Guidelines Index
Antiemesis Table of Contents
Discussion, ReferencesAntiemesis
Practice Guidelines
in Oncology – v.2.2010
®
NCCN
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
AE-2
aHigh
b,cStart before chemotherapy
d·Serotonin (5-HT3) antagonist:
>Dolasetron 100 mg PO or 1.8 mg/kg IV or 100 mg IV day 1
or
>Granisetron 2 mg PO or 1 mg PO bid or 0.01 mg/kg (max 1 mg) IV day 1 or transdermal patch
containing 34.3 mg granisetron applied approximately 24-48 h prior to first dose of chemotherapy,
maximum duration of patch is 7 days
or
>Ondansetron 16-24 mg PO or 8-12 mg (max 32 mg/day) IV day 1
or
>Palonosetron 0.25 mg IV day 1
AND
·Steroid:
>Dexamethasone 12 mg PO or IV day 1, 8 mg PO daily days 2-4
AND
·Neurokinin 1 antagonist:
>Aprepitant 125 mg PO day 1, 80 mg PO daily days 2-3
or
>Fosaprepitant 115 mg IV on day 1 only, then aprepitant 80 mg PO daily days 2-3
·± Lorazepam 0.5 -2 mg PO or IV or sublingual either every 4 hours or 6 hours day 1-4
·± H2 blocker or proton pump inhibitor
b,cHIGH EMETIC RISK INTRAVENOUS CHEMOTHERAPY - EMESIS PREVENTION
category 1
for combined
cregimens
See
Breakthrough
Treatment
(AE-6)
a 2Data for post-cisplatin (³ 50 mg/m ) emesis prevention are category 1, others are category 2A.
bAntiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient specific risk factors.
c
dOrder of listed antiemetics does not reflect preference.
See Principles for Managing Multi-day Emetogenic Chemotherapy Regimens (AE-A).
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b,cMODERATE EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONINTRAVENOUS
e Moderate
e 2Data for post-carboplatin ³ 300 mg/m , cyclophosphamide ³ 600-1000
2 2mg/m , doxorubicin ³ 50 mg/m emesis prevention are category 1.
fAs per high emetic risk prevention, aprepitant should be added (to
dexamethasone and a 5-HT3 antagonist regimen) for select patients
receiving other chemotherapies of moderate emetic risk (for example,
carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan or
methotrexate) ( ).See AE-2
b
as well as patient specific risk factors.
c
dOrder of listed antiemetics does not reflect preference.
Antiemetic regimens should be chosen based on the drug with the highest emetic risk
See Principles for Managing Multi-day Emetogenic Chemotherapy Regimens (AE-A).
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
AE-3
b,cStart before chemotherapy
·
>
(category 1)
or
>Granisetron 1-2 mg PO or 1 mg PO bid (category 1)
or 0.01 mg/kg (maximum 1 mg) IV or transdermal
patch containing 34.3 mg granisetron applied
approximately 24-48 h prior to first dose of
chemotherapy; maximum duration of patch is 7 d
or
>Ondansetron 16-24 mg PO or 8-12 mg (maximum 32
mg/day) IV (category 1)
or
>Palonosetron 0.25 mg IV (category 1) day 1 only
AND
·Steroid
>Dexamethasone 12 mg PO or IV
WITH / WITHOUT
·Neurokinin 1 antagonist (for selected patients, where
fappropriate)
>Aprepitant 125 mg PO
or
>Fosaprepitant 115 mg IV day 1 only
·± Lorazepam 0.5-2 mg PO or IV or sublingual either
every 4 or every 6 h prn
·± H2 blocker or proton pump inhibitor
dSerotonin (5-HT3) antagonist:
Dolasetron 100 mg PO or 1.8 mg/kg or 100 mg IV
DAY 1
·
>
100 mg IV
or
>Granisetron 1-2 mg PO daily or 1 mg PO
bid or 0.01 mg/kg (maximum 1 mg) IV
or
>Ondansetron 8 mg PO bid or 16 mg PO
daily or 8 mg (maximum 32 mg/day) IV
OR
·Steroid monotherapy:
>Dexamethasone 8 mg PO or IV daily
OR
·Neurokinin 1 antagonist ± steroid (if NK-1
fantagonist used on day 1)
>Aprepitant 80 mg PO ± dexamethasone
8 mg PO or IV daily
·± Lorazepam 0.5-2 mg PO or IV or sublingual
either every 4 or every 6 h prn
·± H2 blocker or proton pump inhibitor
dSerotonin (5-HT3) antagonist monotherapy:
Dolasetron 100 mg PO daily or 1.8 mg/kg or
DAYS 2 and 3
See
Breakthrough
Treatment
(AE-6)
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Guidelines Index
Antiemesis Table of Contents
Discussion, ReferencesAntiemesis
Practice Guidelines
in Oncology – v.2.2010
®
NCCN
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Low
Minimal
b,cStart before chemotherapy
·
>Dexamethasone 12 mg PO or IV daily
or
g>Metoclopramide 10-40 mg PO or IV and then either every 4 or every 6 h prn
or
g>Prochlorperazine 10 mg PO or IV and then every 4 or every 6 h prn
·± Lorazepam, 0.5-2 mg PO or IV either every 4 or every 6 h prn
·± H2 blocker or proton pump inhibitor
Repeat daily for fractionated doses of chemotherapy
AE-4
b,cLOW AND MINIMAL EMETIC RISK INTRAVENOUS CHEMOTHERAPY - EMESIS PREVENTION
b
c
gMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or every 6 h for dystonic reactions.
Antiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient specific risk factors.
See Principles for Managing Multi-day Emetogenic Chemotherapy Regimens (AE-A).
See Principles of Emesis Control
for the Cancer Patient (AE-1)
No routine
prophylaxis
Breakthrough Treatment For
Chemotherapy Induced
Nausea/vomiting (AE-6)
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b,c,hORAL CHEMOTHERAPY - EMESIS PREVENTION
Prophylaxis
recommended
PRN
recommended
Start before chemotherapy
d·Serotonin 5-HT3 antagonist:
>
or
>Granisetron 2 mg PO daily or 1 mg PO BID daily
or
>Ondansetron 16-24 mg PO daily
·± Lorazepam 0.5-2 mg PO or sublingual every 4 or every 6 h prn
·± H2 blocker or proton pump inhibitor
Dolasetron 100 mg PO daily
Nausea/
vomiting
No routine prophylaxis
Start before chemotherapy
>
gevery 4 or every 6 h prn
or
>Prochlorperazine 10 mg PO and then
gevery 4 or every 6 h prn
·± Lorazepam 0.5-2 mg PO every 4 or
every 6 h prn
·± H2 blocker or proton pump inhibitor
Metoclopramide 10-40 mg PO and then
bAntiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient specific risk factors.
c
dOrder of listed antiemetics does not reflect preference.
gMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or every 6 h for dystonic reactions.
hThese antiemetic recommendations apply to oral chemotherapy only. When combined with IV agents in a combination chemotherapy regimen, the antiemetic
recommendations for the perhaps stating that if oral and IV are combined, the agent with the highest level of emetogenicity should be followed. If multiple oral agents
are combined, emetic risk may be increased and require prophylaxis.
See Principles for Managing Multi-day Emetogenic Chemotherapy Regimens (AE-A).
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
AE-5
Continued nausea/vomiting,
recommend any of the oral
5-HT3 antagonists above
Breakthrough Treatment
For Chemotherapy Induced
Nausea/vomiting (AE-6)
See Emetogenic Potential of Oral Antineoplastic Agents (AE-9)
Breakthrough
Treatment For
Chemotherapy Induced
Nausea/vomiting (AE-6)
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Guidelines Index
Antiemesis Table of Contents
Discussion, ReferencesAntiemesis
Practice Guidelines
in Oncology – v.2.2010
®
NCCN
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Any
nausea/
vomiting
General principle of breakthrough treatment is to add one agent
dfrom a different drug class prn to the current regimen
·Antipsychotic:
g>Haloperidol 1-2 mg PO every 4