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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®)
Antiemesis
Version 2.2014
Continue
NCCN.org
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®.
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NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®.
NCCN Guidelines Version 2.2014 Panel Members
Antiemesis
David S. Ettinger, MD/Chair †The Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins
Michael J. Berger, PharmD/Vice Chair, BCOP ΣThe Ohio State University ComprehensiveCancer Center - James Cancer Hospitaland Solove Research Institute
Debra K. Armstrong, RN, OCN #Vanderbilt-Ingram Cancer Center
Sally Barbour, PharmD, BCOP, CCP ΣDuke Cancer Institute
Philip J. Bierman, MD † ‡UNMC Eppley Cancer Center atThe Nebraska Medical Center
Bob Bradbury, BCPS ΣMoftt Cancer Center
Georgiana Ellis, MD †Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
Steve Kirkegaard, PharmD Σ
Huntsman Cancer Instituteat the University of Utah
Dwight D. Kloth, PharmD, BCOP ΣFox Chase Cancer Center
Mark G. Kris, MD †
Memorial Sloan-Kettering Cancer Center
Dean Lim, MD †City of Hope Comprehensive Cancer Center
Belinda Mandrell, PhD, RN †St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute
Laura Boehnke Michaud, PharmD, BCOP ΣThe University of Texas
M.D. Anderson Cancer Center
Kim Noonan, MS, RN, ANP, AOCN #Dana-Farber/Brigham and Women’sCancer Center | Massachusetts GeneralHospital Cancer Center
Hope S. Rugo, MD † ‡UCSF Helen Diller FamilyComprehensive Cancer Center
Bridget Scullion, PharmD, BCOP
Dana-Farber/Brigham and Women’sCancer Center | Massachusetts GeneralHospital Cancer Center
Steven M. Sorscher, MD †Siteman Cancer Center at Barnes-Jewish Hospital and WashingtonUniversity School of Medicine
Lisa Stucky-Marshall, RN, MS,AOCN #Robert H. Lurie ComprehensiveCancer Center of NorthwesternUniversity
Barbara Todaro, PharmD ΣRoswell Park Cancer Institute
Susan G. Urba, MD † £
University of MichiganComprehensive Cancer Center
NCCN
Maoko Naganuma, MSc
Dorothy A. Shead, MS Continue
NCCN Guidelines Panel Disclosures
‡ Hematology/hematology oncology
Þ Internal medicine
† Medical oncology
# Nurse
Σ Pharmacology
£ Supportive care including palliative,
pain management, pastoral care,
and oncology social work* Writing committee member
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Clinical Trials: NCCN believes that
the best management for any cancerpatient is in a clinical trial.Participation in clinical trials isespecially encouraged.
To nd clinical trials online at NCCNmember institutions, click here:nccn.org/clinical_trials/physician.html.
NCCN Categories of Evidence andConsensus: All recommendationsare Category 2A unless otherwise
specied.See NCCN Categories of Evidenceand Consensus.
NCCN Antiemesis Panel Members
Guidelines UpdatesPrinciples of Emesis Control for the Cancer Patient (AE-1)
CHEMOTHERAPY-INDUCED EMESIS:
High Emetic Risk Intravenous Chemotherapy -
Acute and Delayed 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 Multiday Emetogenic Chemotherapy Regimens (AE-A)
Principles for Managing Breakthrough Emesis (AE-B)
RADIATION-INDUCED EMESIS:
Radiation-Induced Emesis Prevention/Treatment (AE-10)
ANTICIPATORY EMESIS:
Anticipatory Emesis Prevention/Treatment (AE-11)
The NCCN 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 the NCCN 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® (NCCN®) makes no representations or
warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®
. All rights reserved. The NCCN Guidelines and the illustrations herein maynot be reproduced in any form without the express written permission of NCCN. ©2014.
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®.
NCCN Guidelines Version 2.2014 Table of Contents
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Printed by Ayu Rahmawati on 7/2/2014 9:58:56 AM. For personal use only. Not approved for distribution. Copyright © 2014 National Comprehensive Cancer Network, Inc., All Rights Reserved.
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NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 1.2014, 08/19/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®. UPDATES
NCCN Guidelines ® Version 2.2014 Updates
Antiemesis
Updates in Version 2.2014 of the NCCN Guidelines for Antiemesis from Version 1.2014 include:
AE-2
• High emetic risk intravenous chemotherapy - acute and delayed
emesis prevention:
Added “daily” to the recommendation for granisetron.
“Granisetron 2 mg PO daily or 1 mg PO BID...”
Removed “max 32 mg/day” IV dose for ondansetron.
Added olanzapine-containing regimen
◊ Olanzapine 10 mg PO days 1-4
◊ Palonosetron 0.25 mg IV day 1
◊ Dexamethasone 20 mg IV day 1
Added the following reference; Navari RM, Gray SE, Kerr AC.
Olanzapine versus aprepitant for the prevention of chemotherapy-
induced nausea and vomiting: a randomized phase III trial. J Support
Oncol 2011;9:188-195.
AE-3
• Moderate emetic risk intravenous chemotherapy - emesis prevention:
Added “daily” to the recommendation for granisetron.
“Granisetron 2 mg PO daily or 1 mg PO BID...”
Removed “max 32 mg/day” IV dose for ondansetron.Added olanzapine-containing regimen
◊ Olanzapine 10 mg PO days 1-4
◊ Palonosetron 0.25 mg IV day 1
◊ Dexamethasone 20 mg IV day 1
Added the following reference; Navari RM, Gray SE, Kerr AC.
Olanzapine versus aprepitant for the prevention of chemotherapy-
induced nausea and vomiting: a randomized phase III trial.
J Support Oncol 2011;9:188-195.
Under days 2 and 3 added: “Fosaprepitant (if given day 1 only) ±
dexamethasone 8 mg PO or IV (days 2 and 3).”
AE-4
• Low and minimal emetic risk intravenous chemotherapy - emesis
prevention:
Following Low, added “Serotonin (5-HT3) antagonist (Choose
one):”
◊ Dolasetron 100 mg PO daily
◊ Granisetron 2 mg PO daily or 1 mg PO BID
◊
Ondansetron 16-24 mg PO dailyAdded footnote e: “Order of listed antiemetics is alphabetical.”
Removed the IV administration of prochlorperazine
AE-5
• Oral chemotherapy - emesis prevention
Following Low to minimal emetic risk, added
“Serotonin (5-HT3) antagonist (Choose one):”
◊ Dolasetron 100 mg PO daily
◊ Granisetron 2 mg PO daily or 1 mg PO BID
◊ Ondansetron 16-24 mg PO daily
Removed the IV administration of prochlorperazine
AE-6• Breakthrough treatment for chemotherapy-induced nausea/vomiting:
Added atypical antipsychotic: olanzapine 10 mg PO daily for 3 days
with the following reference; Navari RM, Nagy CK, Gray SE. The
use of olanzapine versus metoclopramide for the treatment of
breakthrough chemotherapy-induced nausea and vomiting in
patients receiving highly emetogenic chemotherapy. Support Care
Cancer 2013;21:1655-1663.
Removed the IV administration of prochlorperazine
Removed the following footnote: See blackbox warning/label
indication regarding type II diabetes, hyperglycemia, and death in
elderly dementia patients.Continued on next page
Updates in Version 1.2014 of the NCCN Guidelines for Antiemesis from Version 1.2013 include:
AE-4, AE-5, and AE-6
• Added the IV administration of prochlorperazine.
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P i t d b A R h ti 7/2/2014 9 58 56 AM F l l N t d f di t ib ti C i ht © 2014 N ti l C h i C N t k I All Ri ht R d
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NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®. UPDATES
NCCN Guidelines Version 2.2014 Updates
Antiemesis
Updates in Version 1.2014 of the NCCN Guidelines for Antiemesis from Version 1.2013 include:
AE-8
• Emetogenic potential of Intravenous antineoplastic agents
Added the following agents to low emetic risk:◊ Ado-trastuzumab ematansine
◊ Omacetaxine
◊ Ziv-aibercept
AE-9
• Emetogenic potential of oral antineoplastic agents
Added the following agents to minimal to low emetic risk:
◊ Cabozantinib
◊ Dabrafenib
◊ Pomalidomide
◊ Ponatinib
◊ Trametinib
Added a footnote to temozolomide stating:
“Temozolomide ≤75 mg/m2 should be considered moderately
emetogenic with concurrent radiotherapy.”
AE-10
• Radiation-induced emesis
Replaced footnote “w” with footnote “f” ◊ Footnote “f” states “Serotonin (5-HT3) antagonists may increase
the risk of developing prolongation of the QT interval of the
electrocardiogram. See Discussion.”
Previous footnote w stated “Ondansetron may increase the
risk of developing prolongation of the QT interval of the
electrocardiogram, which can lead to an abnormal and potentially
fatal heart rhythm, including Torsade de Pointes. Patients at
particular risk for developing Torsade de Pointes include those
with underlying heart conditions, such as congenital long QT
syndrome, those who are predisposed to low levels of potassium
and magnesium in the blood, and those taking other medications
that lead to QT prolongation.”
AE-A
• Principles of managing multiday emetogenic chemotherapy regimens:
Under neurokinin antagonists: added a new bullet “Data from a
small phase III randomized study support the use of aprepitant (125
mg day 3, 80 mg days 4-7) with 5-HT3 antagonist (days 1-5) and
dexamethasone (20 mg days 1, 2) in patients with germ line cancers
treated with 5-day cisplatin-based chemotherapy.
Reference: Albany C, Brames MJ, Fausel C, et al. Randomized,double-blind, placebo-controlled, phase III cross-over study
evaluating the oral neurokinin-1 antagonist aprepitant in
combination with a 5HT3 receptor antagonist and dexamethasone in
patients with germ cell tumors receiving 5-day cisplatin combination
chemotherapy regimens: a hoosier oncology group study. J Clin
Oncol 2012;30:3998-4003.”
Printed by Ayu Rahmawati on 7/2/2014 9:58:56 AM. For personal use only. Not approved for distribution. Copyright © 2014 National Comprehensive Cancer Network, Inc., All Rights Reserved.
Printed by Ayu Rahmawati on 7/2/2014 9:58:56 AM For personal use only Not approved for distribution Copyright © 2014 National Comprehensive Cancer Network Inc All Rights Reserved
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
• 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
and 2 days for moderate after the last dose of chemotherapy. Patients need to be protected throughout the full period of risk.• Oral and intravenous 5-HT3 antagonists have equivalent efcacy when used at the appropriate doses.
• Consider the toxicity of the specic antiemetic(s).
• Choice of antiemetic(s) used should be based on the emetic risk of the therapy, prior experience with antiemetics, and 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, or hyponatremia
Uremia
Concomitant drug treatments, including opiates
Gastroparesis: tumor or chemotherapy (eg, vincristine) induced or other causes (eg, diabetes)
Psychophysiologic:
◊ Anxiety
◊ Anticipatory nausea/vomiting
• For use of antiemetics for nausea/vomiting that are not related to radiation and/or chemotherapy, see NCCN Guidelines for Palliative Care.
• For multi-drug regimens, select antiemetic therapy based on the drug with the highest emetic risk. See Emetogenic Potential of
Intravenous Antineoplastic Agents (AE-7).
• Consider using an H2 blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea.
• Lifestyle measures may help to alleviate nausea/vomiting, such as eating small frequent meals, choosing healthful foods, controlling the
amount of food consumed, and eating food at room temperature. A dietary consult may also be useful. See NCI’s “What You ShouldKnow About Cancer Treatment, Eating Well, and Eating Problems.” (http://www.cancer.gov/cancertopics/coping/eatinghints/page2#4)
AE-1
PRINCIPLES OF EMESIS CONTROL FOR THE CANCER PATIENT
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Printed by Ayu Rahmawati on 7/2/2014 9:58:56 AM. For personal use only. Not approved for distribution. Copyright © 2014 National Comprehensive Cancer Network, Inc., All Rights Reserved.
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
Start before chemotherapyc,d
Neurokinin 1 antagonist containing regimen consisting of the following:• Serotonin (5-HT3) antagonist (Choose one):e,f
Dolasetron 100 mg POgGranisetron 2 mg PO daily or 1 mg PO BID or 0.01 mg/kg (max 1 mg) IV day 1 g or transdermal patch as
3.1 mg/24 h patch (containing 34.3 mg granisetron total dose) applied approximately 24-48 h prior to rstdose of chemotherapy; maximum duration of patch is 7 daysOndansetron 16-24 mg PO or 8-16 mg IV day 1g,h
Palonosetron 0.25 mg IV day 1 (preferred)i
AND• Steroid (Choose one): j
Dexamethasone 12 mg PO or IV day 1, 8 mg PO daily days 2-4 (with aprepitant 125 mg)
Dexamethasone 12 mg PO or IV day 1, 8 mg PO day 2, then 8 mg PO BID days 3 and 4
(with fosaprepitant 150 mg IV day 1)
AND• Neurokinin 1 antagonist (Choose one):Aprepitant 125 mg PO day 1, 80 mg PO daily days 2-3Fosaprepitant 150 mg IV day 1 only
• ± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 hours or every 6 hours days 1-4• ± H2 blocker or proton pump inhibitor
OR
• Olanzapine-containing regimenk
Olanzapine 10 mg PO days 1-4
Palonosetron 0.25 mg IV day 1Dexamethasone 20 mg IV day 1
• ± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 hours or every 6 hours days 1-4• ± H2 blocker or proton pump inhibitor
AE-2
aData for post-cisplatin (≥50 mg/m2) emesis prevention are category 1; others are category 2A.bSee Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7).c Antiemetic regimens should be chosen based on the drug with the highest emetic risk as well
as patient-specific risk factors.dSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A).eOrder of listed antiemetics is alphabetical.f Serotonin (5-HT3) antagonists may increase the risk of developing prolongation of the QT
interval of the electrocardiogram. See Discussion.
gSome NCCN Member Institutions use a 5-HT3 antagonist on days 2-3.hThe FDA recommends a maximum of 16 mg for a single dose of IV ondansetron.iData with palonosetron are based on randomized studies in combination with steroids only.
jUse of steroids is contraindicated with drugs such as interleukin-2 (ie, IL-2, aldesleukin)and interferon.
kNavari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention ofchemotherapy-induced nausea and vomiting: a randomized phase III trial. J SupportOncol 2011;9:188-195.
HIGH EMETIC RISK INTRAVENOUS CHEMOTHERAPY - ACUTE AND DELAYED EMESIS PREVENTIONa,b,c
See Breakthrough
Treatment (AE-6)
See Breakthrough Treatment (AE-6)
category 1
for combinedregimensc
ted by yu a a at o / / 0 9 58 56 o pe so a use o y ot app o ed o d st but o Copy g t © 0 at o a Co p e e s e Ca ce et o , c , g ts ese ed
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®.
Start before chemotherapyc,d
5HT3 antagonist + steroid ± NK1 antagonist regimen consisting of the following:• Serotonin (5-HT3) antagonist (category 1) (Choose one):e,f
Dolasetron 100 mg PO
Granisetron 2 mg PO daily or 1 mg PO BID or 0.01 mg/kg (max 1 mg) IV day 1
or transdermal patch as 3.1 mg/24 h patch (containing 34.3 mg granisetron
total dose) applied approximately 24 to 48 h prior to rst dose of
chemotherapy; maximum duration of patch is 7 days
Ondansetron 16-24 mg PO or 8-16 mg IVh
Palonosetron 0.25 mg IV (preferred)i
AND
• Steroid: j
Dexamethasone 12 mg PO or IV
WITH/WITHOUT• Neurokinin 1 antagonist (Choose one; for selected patients, where
appropriate)l
Aprepitant 125 mg PO
Fosaprepitant 150 mg IV
• ± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 or every 6 h PRN
• ± H2 blocker or proton pump inhibitor
AE-3
MODERATE EMETIC RISK INTRAVENOUS CHEMOTHERAPY - EMESIS PREVENTIONb,c,l
bSee Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7).c Antiemetic regimens should be chosen based on the drug with the highest emetic risk as
well as patient-specific risk factors.dSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A).eOrder of listed antiemetics is alphabetical.f Serotonin (5-HT3) antagonist may increase the risk of developing prolongation of the QT
interval of the electrocardiogram. See Discussion.h
The FDA recommends a maximum of 16 mg for a single dose of IV ondansetron.iData with palonosetron are based on randomized studies with steroids only.
jUse of steroids is contraindicated with drugs such as interleukin-2 (ie, IL-2, aldesleukin) andinterferon.
kNavari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention ofchemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol2011;9:188-195.
lData for post-carboplatin ≥300 mg/m2, cyclophosphamide ≥600-1000 mg/m2, and doxorubicin≥50 mg/m2 emesis prevention are category 1.
m As per high emetic risk prevention, aprepitant or fosaprepitant should be added (to
dexamethasone and a 5-HT3 antagonist regimen) for select patients receiving otherchemotherapies of moderate emetic risk (eg, carboplatin, doxorubicin, epirubicin, ifosfamide,irinotecan, methotrexate) (See AE-2).
DAY 1
OR
• Olanzapine-containing regimenk
Olanzapine 10 mg PO
Palonosetron 0.25 mg IVDexamethasone 20 mg IV
• ± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 or every 6 h PRN
• ± H2 blocker or proton pump inhibitor
OR
DAYS 2 and 3
• Serotonin (5-HT3) antagonist monotherapy (unless
palonsetron used on Day 1) (Choose one):
e,f
Dolasetron 100 mg PO daily
Granisetron 1-2 mg PO daily or 1 mg PO BID or 0.01
mg/kg (maximum 1 mg) IV
Ondansetron 8 mg PO BID or 16 mg PO daily or 8-16
mg IVh
OR • Steroid monotherapy: j
Dexamethasone 8 mg PO or IV daily
OR
• Neurokinin 1 antagonist ± steroid: (if NK-1 antagonist
used on day 1)m
Aprepitant used day 1: Aprepitant 80 mg PO ±dexamethasone 8 mg PO or IV daily
Fosaprepitant used day 1: ± 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
See
Breakthrough
Treatment
(AE-6)
• Olanzapine 10 mg PO days 2-4 (if given day 1)k
• ± Lorazepam 0.5-2 mg PO or IV or sublingual eitherevery 4 or every 6 h PRN
• ± H2 blocker or proton pump inhibitor
See
Breakthrough Treatment
(AE-6)
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
Start before chemotherapyc,d• Repeat daily for multiday doses of chemotherapyd,e
Dexamethasone 12 mg PO or IV daily j
or
Metoclopramide 10-40 mg PO or IV and then either every 4 or every 6 h PRNn
or
Prochlorperazine 10 mg PO or IV and then every 6 h PRN (maximum 40 mg/
day)n
or
Serotonin (5-HT3) antagonist (Choose one):e,f
◊ Dolasetron 100 mg PO daily
◊ Granisetron 2 mg PO daily or 1 mg PO BID
◊ Ondansetron 16-24 mg PO daily
• ± Lorazepam, 0.5-2 mg PO or IV either every 4 or every 6 h PRN
• ± H2 blocker or proton pump inhibitor
AE-4
LOW AND MINIMAL EMETIC RISK INTRAVENOUS CHEMOTHERAPY - EMESIS PREVENTIONc,d,o
c Antiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient-specific risk factors.dSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A).eOrder of listed antiemetics is alphabetical.f Serotonin (5-HT3) antagonist may increase the risk of developing prolongation of the QT interval of the electrocardiogram. See Discussion.
jUse of steroids is contraindicated with drugs such as interleukin-2 (ie, IL-2, aldesleukin) and interferon.nMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or every 6 h for dystonic reactions. If allergic to diphenhydramine, use
benztropine at 1-2 mg IV or IM x 1 dose, followed by oral dose of 1-2 mg daily or BID if needed to control the reaction.oSee Emetogenic Potential of Intravenous Antineoplastic Agents (AE-8).
Low
Minimal No routine prophylaxis
Breakthrough Treatment
for Chemotherapy-Induced
Nausea/Vomiting (AE-6)
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
Start before chemotherapy and continue dailyMetoclopramide 10-40 mg PO and then every 4 or
every 6 h PRNn
or
Prochlorperazine 10 mg PO or IV and then every 6 hPRN (maximum 40 mg/day)n
or Haloperidol 1-2 mg PO every 4 or every 6 h PRNn
or Serotonin (5-HT3) antagonist (Choose one):e,f
◊ Dolasetron 100 mg PO daily◊ Granisetron 2 mg PO daily or 1 mg PO BID ◊ Ondansetron 16-24 mg PO daily
• ± Lorazepam 0.5-2 mg PO every 4 or every 6 h PRN• ± H2 blocker or proton pump inhibitor
AE-5
ORAL CHEMOTHERAPY - EMESIS PREVENTIONc,d,p,q
High tomoderate
emetic risk
Low to
minimal
emetic risk
PRN
recommended
Nausea/
vomiting
Start before chemotherapy and continue daily• Serotonin (5-HT3) antagonist (Choose one):e,f
Dolasetron 100 mg PO dailyGranisetron 2 mg PO daily or 1 mg PO BIDOndansetron 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
Breakthrough Treatment for Chemotherapy-Induced Nausea/Vomiting (AE-6)
Continued
nausea/vomiting,
recommend any
of the oral 5-HT3
antagonists above
c Antiemetic regimens should be chosen based on the drug with the highest emeticrisk as well as patient-specific risk factors.
dSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A).eOrder of listed antiemetics is alphabetical.f Serotonin (5-HT3) antagonists may increase the risk of developing prolongation of
the QT interval of the electrocardiogram. See Discussion.
nMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV eitherevery 4 or every 6 h for dystonic reactions. If allergic to diphenhydramine, usebenztropine at 1-2 mg IV or IM x 1 dose, followed by oral dose of 1-2 mg daily orBID if needed to control the reaction.
pSee Emetogenic Potential of Oral Antineoplastic Agents (AE-9).qThese antiemetic recommendations apply to oral chemotherapy only. When
combined with IV agents in a combination chemotherapy regimen, the antiemeticrecommendations for the agent with the highest level of emetogenicity shouldbe followed. If multiple oral agents are combined, emetic risk may increase andrequire prophylaxis.
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
The general principle of breakthrough treatment is to add one agent
from a different drug class to the current regimen.e
• Atypical antipsychotic:
Olanzapine 10 mg PO daily for 3 dayss
• Benzodiazepine:
Lorazepam 0.5-2 mg PO or IV either every 4 or every 6 h
• Cannabinoid:
Dronabinol 5-10 mg PO either every 3 or every 6 h
Nabilone 1-2 mg PO BID
• Other:
Haloperidol 0.5-2 mg PO or IV every 4-6 hn
Metoclopramide 10-40 mg PO or IV either every 4 or every 6 hn
Scopolamine transdermal patch 1 patch every 72 h• Phenothiazine:
Prochlorperazine 25 mg supp pr every 12 h or 10 mg PO or IV
every 6 hn
Promethazine 12.5-25 mg PO or IV central line only every 4 hn
• Serotonin 5-HT3 antagonists:f
Dolasetron 100 mg PO daily
Granisetron 1-2 mg PO daily or 1 mg PO BID or 0.01 mg/kg
(maximum 1 mg) IV
Ondansetron 16 mg PO or IV daily
• Steroid:Dexamethasone 12 mg PO or IV daily
AE-6
BREAKTHROUGH TREATMENT FOR CHEMOTHERAPY-INDUCED NAUSEA/VOMITINGd,r
dSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A).eOrder of listed antiemetics is alphabetical.f Serotonin (5-HT3) antagonists may increase the risk of developing prolongation of the QT interval of the electrocardiogram. See Discussion.nMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or every 6 h for dystonic reactions. If allergic to diphenhydramine use
benztropine at 1-2 mg IV or IM x 1 dose, followed by oral dose of 1-2 mg daily or BID if needed to control the reaction.r See Principles of Managing Breakthrough Treatment (AE-B).sNavari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients
receiving highly emetogenic chemotherapy. Support Care Cancer 2013;21:1655-1663.
RESPONSE TO
BREAKTHROUGH
ANTIEMETIC TREATMENT
SUBSEQUENT
CYCLES
Any
nausea/vomiting
Nausea and
vomiting
controlled
Nausea and/
or vomiting
uncontrolled
Continue
breakthrough
medications, on a
schedule, not PRN
Re-evaluate and
consider dose
adjustments and/or
switching to a
different therapy
Consider
changing
antiemetic therapy
to higher level
primary treatmentfor next cycle
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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-7
Low Emetic Risk (See AE-8)
Minimal Emetic Risk (See AE-8)
Oral Chemotherapy (See AE-9)
tProportion of patients who experience emesis in the absence of effective antiemetic prophylaxis.uContinuous infusion may make an agent less emetogenic.vThese agents may be highly emetogenic in certain patients.wPotential drug interactions between antineoplastic agents / antiemetic therapies and various other drugs should always be considered.
Adapted with permission from:Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103-109Grunberg SM, Warr D, Gralla RJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity-state of the art. Support Care Cancer. 2010;19:S43-47.
EMETOGENIC POTENTIAL OF INTRAVENOUS ANTINEOPLASTIC AGENTSw
High emetic risk
(>90% frequency of emesis)t,u
Moderate emetic risk
(30%-90% frequency of emesis)t,u
• AC combination dened as either
doxorubicin or epirubicin withcyclophosphamides
• Carmustine >250 mg/m2
• Cisplatin
• Aldesleukin >12-15 million IU/m2
• Amifostine >300 mg/m2
• Arsenic trioxide
• Azacitidine
• Bendamustine
• Busulfan
• Carboplatinv
• Carmustinev ≤250 mg/m2
• Cyclophosphamide >1,500 mg/m2
• Dacarbazine• Doxorubicin ≥60 mg/m2
• Clofarabine
• Cyclophosphamide ≤1500 mg/m2
• Cytarabine >200 mg/m2
• Dactinomycinv
• Daunorubicinv
• Doxorubicinv <60 mg/m2
• Epirubicinv ≤90 mg/m2
• Idarubicin
• Epirubicin >90 mg/m2
• Ifosfamide ≥2 g/m2 per dose• Mechlorethamine
• Streptozocin
• Ifosfamidev <2 g/m2 per dose
• Interferon alfa ≥10 million IU/m2
• Irinotecanv
• Melphalan
• Methotrexatev ≥250 mg/m2
• Oxaliplatin
• Temozolomide
LEVEL AGENT
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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-8
tProportion of patients who experience emesis in the absence of effective antiemetic prophylaxis.wPotential drug interactions between antineoplastic agents / antiemetic therapies and various other drugs should always be considered.
High Emetic Risk (See AE-7)
Moderate Emetic Risk (See AE-7)
Oral Chemotherapy (See AE-9)
Adapted with permission from:Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103-109Grunberg SM, Warr D, Gralla RJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity-state of the art.Support Care Cancer. 2010;19:S43-47.
EMETOGENIC POTENTIAL OF INTRAVENOUS ANTINEOPLASTIC AGENTSw
LEVEL AGENT
Low emetic risk
(10%-30% frequency of emesis)t
• Ado-trastuzumab emtansine
• Amifostine ≤300 mg• Aldesleukin ≤12 million IU/m2
• Brentuximab vedotin
• Cabazitaxel
• Carlzomib
• Cytarabine (low dose)
100-200 mg/m2
• Docetaxel
• Doxorubicin (liposomal)
• Eribulin
• Etoposide
• 5-FU• Floxuridine
• Gemcitabine
• Interferon alfa >5 <10 million
international units/m2
• Ixabepilone
• Methotrexate
>50 mg/m2 <250 mg/m2
• Mitomycin
• Mitoxantrone
• Omacetaxine
• Paclitaxel• Paclitaxel-albumin
• Pemetrexed
• Pentostatin
• Pralatrexate
• Romidepsin
• Thiotepa
• Topotecan
• Ziv-aibercept
Minimal emetic risk(<10% frequency of emesis)t
• Alemtuzumab• Asparaginase
• Bevacizumab
• Bleomycin
• Bortezomib
• Cetuximab
• Cladribine
(2-chlorodeoxyadenosine)
• Cytarabine <100 mg/m2
• Decitabine
• Denileukin diftitox• Dexrazoxane
• Fludarabine
• Interferon alpha ≤5 million
IU/m2
• Ipilimumab
• Methotrexate ≤50 mg/m2
• Nelarabine
• Ofatumumab
• Panitumumab
• Pegaspargase• Peginterferon
• Pertuzumab
• Rituximab
• Temsirolimus
• Trastuzumab
• Valrubicin
• Vinblastine
• Vincristine
• Vincristine (liposomal)
• Vinorelbine
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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-9
wPotential drug interactions between antineoplastic agents / antiemetic therapies and various other drugs should always be considered.xTemozolomide ≤75 mg/m2/day should be considered moderately emetogenic with concurrent radiotherapy.
Adapted with permission from:Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15:103-109Grunberg SM, Warr D, Gralla RJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity-state of the art. Support Care Cancer. 2010;19:S43-47.
High Emetic Risk (See AE-7)
Moderate Emetic Risk (See AE-7)
Low Emetic Risk (See AE-8)
Minimal Emetic Risk (See AE-8)
EMETOGENIC POTENTIAL OF ORAL ANTINEOPLASTIC AGENTSw
LEVEL AGENT
Moderate to high • Altretamine
• Busulfan (≥4 mg/day)
• Crizotinib
• Cyclophosphamide
(≥100 mg/m2 /day)
• Estramustine
• Etoposide
• Lomustine (single day)
• Mitotane
• Procarbazine
• Temozolomide (>75 mg/m2 /day)
• Vismodegib
Minimal to low • Axitinib
• Bexarotene
• Bosutinib
• Busulfan (<4 mg/day)
• Cabozantinib
• Capecitabine
• Chlorambucil
• Cyclophosphamide(<100 mg/m2 /day)
• Dasatinib
• Dabrafenib
• Erlotinib
• Everolimus
• Fludarabine
• Getinib
• Hydroxyurea
• Imatinib
• Lapatinib
• Lenalidomide
• Melphalan
• Mercaptopurine
• Methotrexate• Nilotinib
• Pazopanib
• Pomalidomide
• Ponatinib
• Regorafenib
• Ruxolitinib
• Sorafenib
• Sunitinib
• Temozolomide (≤75 mg/m2 /day)x
• Thalidomide
• Thioguanine
• Topotecan
• Trametinib• Tretinoin
• Vandetanib
• Vemurafenib
• Vorinostat
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
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.
Radiation-inducednausea/vomiting
AE-10Version 1.2014, 08/19/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of NCCN ®.
eOrder of listed antiemetics is alphabetical.f Serotonin (5-HT3) antagonists may increase the risk of developing prolongation of the QT interval of the electrocardiogram. See Discussion.
RADIATION-INDUCED EMESIS PREVENTION/TREATMENT
EMETOGENIC
POTENTIAL
TYPE OF RADIATION THERAPY BREAKTHROUGH TREATMENT
Radiation therapy (RT) -
upper abdomen/localized
sites
Total body irradiation(TBI)
Chemotherapy and RT
(including TBI)
Start pretreatment for each day of RT treatment:e
• Granisetron 2 mg PO daily
or
• Ondansetron 8 mg PO BID
• ± Dexamethasone 4 mg PO daily
Start pretreatment for each day of RT treatment:e
• Granisetron 2 mg PO dailyor
• Ondansetron 8 mg PO BID-TIDf
• ± Dexamethasone 4 mg PO daily
See emesis prevention for chemotherapy-induced nausea/vomiting
(High AE-2, Moderate AE-3, Low AE-4, and Oral AE-5)
See Breakthrough
Treatment (AE-6)
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
Prevention is key:
• Use optimal antiemetic therapy during every cycle of treatment
Behavioral therapy:
• Relaxation/systematic desensitization
• Hypnosis/guided imagery
• Music therapy
Acupuncture/acupressure
Alprazolam 0.5-2 mg PO TID beginning on the night before treatment
or
Lorazepam 0.5-2 mg PO on the night before and morning of treatment
See Primary and Breakthrough Treatments for Chemotherapy-Induced Nausea/Vomiting (Antiemesis TOC)
AE-11
ANTICIPATORY EMESIS PREVENTION/TREATMENT
Anticipatorynausea/vomiting
See Principles of Emesis Control
for the Cancer Patient (AE-1)
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
Summary:
• Patients receiving multiday chemotherapy are at risk for both acute and delayed nausea/vomiting based on the emetogenic potential of the
individual chemotherapy agents administered on any given day and their sequence. It is therefore difcult to recommend a specicantiemetic regimen for each day, especially since acute and delayed emesis may overlap after the initial day of chemotherapy until the last
day of chemotherapy.
• After chemotherapy administration concludes, the period of risk for delayed emesis also depends on the specic regimen and the
emetogenic potential of the last chemotherapy agent administered in the regimen.
• Practical issues also need to be considered when designing the antiemetic regimen, taking into account the administration setting (eg,
inpatient versus outpatient), preferred route of administration (IV versus oral), duration of action of the serotonin antagonist and appropriate
associated dosing intervals, tolerability of daily antiemetics (eg, corticosteroids), and adherence/compliance issues.
General Principles:
• Corticosteroids:
Dexamethasone should be administered once daily (either orally or intravenously) for moderately or highly emetogenic chemotherapy andfor 2 to 3 days after chemotherapy for regimens that are likely to cause signicant delayed emesis.
Dexamethasone dose may be modied or omitted when the chemotherapy regimen already includes a corticosteroid.
Side effects associated with prolonged dexamethasone administration should be carefully considered.
• Serotonin Antagonists:
A serotonin antagonist should be administered prior to the rst (and subsequent) doses of moderately or highly emetogenic
chemotherapy. The frequency of repeated administration of the serotonin antagonist depends on the agent chosen.
Palonosetron:
◊ A single intravenous palonosetron dose of 0.25 mg may be sufcient prior to the start of a 3-day chemotherapy regimen instead of
multiple daily doses of another oral or intravenous serotonin antagonist.
◊ Repeat dosing of palonosetron 0.25 mg IV is likely to be safe, based on available evidence.
◊ In terms of efcacy, the need for repeat dosing with palonosetron, either daily or less frequently, in the setting of multiday chemotherapy
is not yet known.
AE-A
(1 OF 2)
1The panel acknowledges that evidence is lacking to support every clinical scenario. Decisions should be individualized for each chemotherapy regimen and eachpatient. An extensive knowledge of the available clinical data, pharmacology, pharmacodynamics, and pharmacokinetics of the antiemetics and the chemotherapy andexperience with patients (regarding tolerability and efficacy) are all paramount to successfully implementing these guidelines into clinical practice.
Continued on next page
PRINCIPLES OF MANAGING MULTIDAY EMETOGENIC CHEMOTHERAPY REGIMENS1
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
• Neurokinin Antagonists:
Aprepitant or fosaprepitant may be used for multiday chemotherapy regimens likely to be highly emetogenic and associated with
signicant risk for delayed nausea and emesis.Category 1 evidence is available for single-day chemotherapy regimens only with aprepitant administered orally (as a 3-day regimen) in
combination with a serotonin antagonist and corticosteroid (as noted on AE-2 and AE-3). Alternatively, for highly emetogenic regimens,
fosaprepitant 150 mg IV with recommended dexamethasone dosing may be given on day 1 with no need for oral aprepitant on days 2 and 3.
If the oral aprepitant regimen is chosen, phase II data exists to support administration of aprepitant on days 4 and 5 after multiday
chemotherapy. It is not yet known if dosing aprepitant after day 3 improves control of nausea or emesis in this clinical setting.
If the intravenous fosaprepitant regimen is chosen, pharmacokinetic data suggest that the single 150 mg intravenous dose provides
antiemetic coverage for a similar period (up to 72 hours post chemotherapy). Studies investigating repeat dosing of intravenous
fosaprepitant are not yet available.
Data from a small phase III randomized study support the use of aprepitant (125 mg day 3, 80 mg days 4-7) with 5-HT3 antagonist (days 1-5)
and dexamethasone (20 mg days 1, 2) in patients with germ line cancers treated with a 5-day cisplatin-based chemotherapy. Reference:
Albany C, Brames MJ, Fausel C, et al. Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oralneurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors
receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol 2012;30:3998-4003.
AE-A
(2 OF 2)
1The panel acknowledges that evidence is lacking to support every clinical scenario. Decisions should be individualized for each chemotherapy regimen and eachpatient. An extensive knowledge of the available clinical data, pharmacology, pharmacodynamics, and pharmacokinetics of the antiemetics and the chemotherapy andexperience with patients (regarding tolerability and efficacy) are all paramount to successfully implementing these guidelines into clinical practice.
PRINCIPLES OF MANAGING MULTIDAY EMETOGENIC CHEMOTHERAPY REGIMENS1
NCCN G id li V i 2 2014
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NCCN Guidelines Version 2.2014
Antiemesis
NCCN Guidelines Index
Antiemesis Table of Contents
Discussion
Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines ® and this illustration may not be reproduced in any form without the express written permission of 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.
• Breakthrough emesis presents a difcult situation, as correction of refractory ongoing nausea/vomiting is often challenging to reverse. It is
generally far easier to prevent nausea/vomiting than it is to treat it.
• The general principle of breakthrough treatment is to give an additional agent from a different drug class. No one drug class has been shownto be superior for the management of breakthrough emesis, and the choice of agent should be based on assessment of the current prevention
strategies used. Some patients may require several agents utilizing differing mechanisms of action.
• One should strongly consider routine, around-the-clock administration rather than PRN dosing.
• The PO route is not likely to be feasible due to ongoing vomiting; therefore, rectal or IV therapy is often required.
• Multiple concurrent agents, perhaps in alternating schedules or by alternating routes, may be necessary. Dopamine antagonists (eg,
metoclopramide, haloperidol), corticosteroids, and agents such as lorazepam may be required.
• Ensure adequate hydration or uid repletion, simultaneously checking and correcting any possible electrolyte abnormalities.
• Prior to administering the next cycle of chemotherapy the patient should be reassessed, with attention given to various possible non-
chemotherapy-related reasons for breakthrough emesis with the current cycle:
Brain metastases
Electrolyte abnormalitiesTumor inltration of the bowel or other gastrointestinal abnormality
Other comorbidities
• Prior to the next cycle of chemotherapy, reassess both the day 1 and post-chemotherapy antiemetic regimen, which did not protect the
patient during the present cycle, and consider alternatives: (Suggestions are not in order of preference)
Add aprepitant if not previously included.
Add other concomitant antiemetics, (eg, dopamine antagonists such as metoclopramide or haloperidol).
Possibly adjust dose(s), either intensity or frequency, of the 5-HT3 antagonist. Based on the patient’s experiences, the chemotherapy
regimen in question may actually be more emetogenic than generally classied (eg, Hesketh method).
Possibly switch to a different 5-HT3. Although not necessarily likely to be effective, anecdotal and limited investigational trial data suggest
it may sometimes be efcacious.If the goal of chemotherapy is non-curative, consider other appropriate regimens, if any, that might be less emetogenic.
It may be benecial to add an anxiolytic agent in combination with the antiemetic agents.
• Consider antacid therapy if patient has dyspepsia (H2 blocker or proton pump inhibitor).
AE-B
PRINCIPLES FOR MANAGING BREAKTHROUGH EMESIS
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Version 2.2014, 04/18/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-1
NCCN Guidelines Index Antiemesis Table of Contents
Discussion
NCCN Guidelines Version 2.2014Antiemesis
Discussion
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN
consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform
NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN
consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN
disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Table of Contents
Overview ..................................................................................... MS-2
Pathophysiology of Emesis ...................................................... MS-2
Nausea ........................................................................................ MS-2
Types of Nausea and/or Vomiting ............................................ MS-3
Chemotherapy-Induced Nausea and/or Vomiting ..................... MS-3
Radiation-Induced Nausea and/or Vomiting ............................. MS-3
Emetogenicity of Chemotherapy .............................................. MS-3
Types of Antiemetic Therapies ................................................. MS-4
Serotonin (5-HT3) Receptor Antagonists .................................. MS-4
Neurokinin-1–Receptor Antagonist ........................................... MS-7
Other Non–5-HT3–Receptor Antagonist Antiemetics ................ MS-9
Treatment Issues ...................................................................... MS-10
Principles of Emesis Control ................................................... MS-11
Prevention of Acute and Delayed Emesis ............................... MS-11
Breakthrough Treatment ......................................................... MS-14
Radiation-Induced Nausea and/or Vomiting ............................ MS-15
Anticipatory Nausea and/or Vomiting ...................................... MS-15
Managing Multiday Emetogenic Chemotherapy Regimens ... MS-16
References ................................................................................ MS-19
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NCCN Guidelines IndexA i i T bl f C
NCCN Guidelines Version 2.2014
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Antiemesis Table of ContentsDiscussionAntiemesis
nausea and emesis. As per the labeled indication, aprepitant should be
administered 125 mg orally 1 hour prior to chemotherapy on day 1,
along with a 5-HT3 receptor antagonist and dexamethasone. Aprepitant
80 mg should be administered daily on days 2 and 3 after the start of
chemotherapy along with dexamethasone.158 Repeated dosing of
aprepitant over multiple cycles of cisplatin-based chemotherapy was
shown to be feasible and well tolerated; importantly, protection from
emesis and from significant nausea was maintained during the
subsequent cycles of emetogenic chemotherapy.95,158 Based on phaseII data, aprepitant 80 mg may be safely administered beyond day 3 of
initiating chemotherapy.96,170 Alternatively, for highly emetogenic
chemotherapy regimens, fosaprepitant 150 mg IV with dexamethasone
may be given on day 1 with no need for oral aprepitant on days 2 and 3
with recommended dosing of dexamethasone.
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NCCN Guidelines Index Antiemesis Table of Contents
Discussion
NCCN Guidelines Version 2.2014Antiemesis
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167. Einhorn LH, Brames MJ, Dreicer R, et al. Palonosetron plus
dexamethasone for prevention of chemotherapy-induced nausea andvomiting in patients receiving multiple-day cisplatin chemotherapy forgerm cell cancer. Support Care Cancer 2007;15:1293-1300. Availableat: http://www.ncbi.nlm.nih.gov/pubmed/17436025 .
168. Giralt SA, Mangan KF, Maziarz RT, et al. Three palonosetronregimens to prevent CINV in myeloma patients receiving multiple-dayhigh-dose melphalan and hematopoietic stem cell transplantation. AnnOncol 2010. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/20935058 .
169. Jordan K, Kinitz I, Voigt W, et al. Safety and efficacy of a tripleantiemetic combination with the NK-1 antagonist aprepitant in highlyand moderately emetogenic multiple-day chemotherapy. Eur J Cancer2009;45:1184-1187. Available at:http://www.ncbi.nlm.nih.gov/pubmed/19135359 .
170. Olver IN, Grimison P, Chatfield M, et al. Results of a 7-day
aprepitant schedule for the prevention of nausea and vomiting in 5-daycisplatin-based germ cell tumor chemotherapy. Support Care Cancer2013;21:1561-1568. Available at:http://www.ncbi.nlm.nih.gov/pubmed/23274926 .
171. Albany C, Brames MJ, Fausel C, et al. Randomized, double-blind,placebo-controlled, phase III cross-over study evaluating the oralneurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor
antagonist and dexamethasone in patients with germ cell tumorsreceiving 5-day cisplatin combination chemotherapy regimens: ahoosier oncology group study. J Clin Oncol 2012;30:3998-4003. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22915652 .