antiemesis nccn guidelines.pdf

8/10/2019 antiemesis NCCN Guidelines.pdf

http://slidepdf.com/reader/full/antiemesis-nccn-guidelinespdf 1/50

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 ®.

http://nccn.org/

http://nccn.org/



NCCN Guidelines Index

Antiemesis Table of Contents

Discussion


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

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.

http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

http://www.nccn.org/disclosures/panel_list.asp?ID=49

http://www.nccn.org/disclosures/panel_list.asp?ID=49




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.


NCCN Guidelines Version 2.2014 Table of Contents

Antiemesis



Discussion


http://www.nccn.org/clinical_trials/clinicians.aspx










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):”



◊ Ondansetron 16-24 mg PO daily


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 following footnote: See blackbox warning/label

indication regarding type II diabetes, hyperglycemia, and death in

elderly dementia patients.Continued on next page


AE-4, AE-5, and AE-6

• Added the IV administration of prochlorperazine.


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







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


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





NCCN Guidelines Version 2.2014

Antiemesis



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.

• 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




http://www.nccn.org/professionals/physician_gls/pdf/palliative.pdf

http://www.cancer.gov/cancertopics/coping/eatinghints/page2#4

http://www.cancer.gov/cancertopics/coping/eatinghints/page2#4

http://www.nccn.org/professionals/physician_gls/pdf/palliative.pdf





Antiemesis



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.

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







Antiemesis



Discussion


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


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


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


See

Breakthrough Treatment

(AE-6)







Antiemesis



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.

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



◊ Ondansetron 16-24 mg PO daily

• ± Lorazepam, 0.5-2 mg PO or IV either every 4 or every 6 h PRN


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)







Antiemesis



Discussion




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.







Antiemesis



Discussion




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







Antiemesis



Discussion




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







Antiemesis



Discussion




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







Antiemesis



Discussion




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







Antiemesis



Discussion



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)







Antiemesis



Discussion




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)







Antiemesis



Discussion




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








Antiemesis



Discussion




• 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








Antiemesis



Discussion




• 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






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





NCCN Guidelines IndexA i i T bl f C








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-18

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.



http://www.clevelandclinicmeded.com/medicalpubs/pharmacy/novdec2002/5ht.htm




http://www.merck.com/product/usa/pi_circulars/e/emend_iv/emend_iv_pi_pdf



http://data.memberclicks.com/site/mascc/MASCC_Guidelines_English_2011.pdf

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm149533.htm



NCCN Guidelines Index Antiemesis Table of Contents

Discussion

NCCN Guidelines Version 2.2014Antiemesis






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-31

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 .

antiemesis nccn guidelines.pdf

Documents