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Antiemesis_2011_final_11_29_1.

NCCN Guidelines Index Antiemesis Table of Contents NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™)
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011 Panel Members
David S. Ettinger, MD/Chair †
Steve Kirkegaard, PharmD å
Hope S. Rugo, MD † ‡
The Sidney Kimmel Comprehensive Cancer
Huntsman Cancer Institute at the University
UCSF Helen Diller Family
Center at Johns Hopkins
Comprehensive Cancer Center
Debra K. Armstrong, RN #
Dwight D. Kloth, PharmD, FCCP, BCOP å
Steven M. Sorscher, MD †
Vanderbilt-Ingram Cancer Center
Fox Chase Cancer Center
Siteman Cancer Center at Barnes-
Jewish Hospital and Washington

Sally Barbour, PharmD, BCOP å
Mark G. Kris, MD †
University School of Medicine
Duke Comprehensive Cancer Center
Memorial Sloan-Kettering Cancer Center
Sundae Stelts, PharmD å
Michael J. Berger, PharmD, BCOP å
Dean Lim, MD †
St. Jude Children's Hospital /
The Ohio State University Comprehensive
City of Hope Comprehensive Cancer Center
University of Tennessee Cancer
Cancer Center - James Cancer Hospital and
Solove Research Institute
Michael Anne Markiewicz, PharmD å
University of Alabama at Birmingham
Lisa Stucky-Marshall, RN, MS,
AOCN #

Philip J. Bierman, MD † ‡
Comprehensive Cancer Center
Robert H. Lurie Cancer Center of
UNMC Eppley Cancer Center at The Nebraska
Laura Boehnke Michaud, PharmD, BCOP å
The University of Texas M.D. Anderson
Cancer Center

Barbara Todaro, PharmD å
Bob Bradbury, BCPS å
Roswell Park Cancer Institute
H. Lee Moffitt Cancer Center & Research
Lida Nabati, MD £ Þ
Dana-Farber/Brigham and Women's Cancer
Susan Urba, MD † £
Center Massachusetts General Hospital
University of Michigan
Georgianna Ellis, MD †
Comprehensive Cancer Center
Fred Hutchinson Cancer Research Center/
Seattle Cancer Care Alliance

Kim Noonan, RN, NP, AOCN #
Miranda Hughes, PhD
Dana-Farber/Brigham and Women's Cancer
Dorothy A. Shead, MS
Center Massachusetts General Hospital
Cancer Center

Specialties Index‡ Hematology/hematology oncologyÞ Internal medicine† Medical Oncology# Nurse å Pharmacology£ Supportive Care including Palliative, Pain management, Pastoral care and Oncology Note: All recommendations are category 2A unless otherwise indicated.
l trials is especially encouraged.
* Writing Committee member Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011 Table of Contents
Clinical Trials: The NCCN
believes that the best management for any cancer patient is in a clinicaltrial. Participation in clinical trials is CHEMOTHERAPY INDUCED EMESIS: To find clinical trials online at NCCN NCCN Categories of Evidence and
Consensus: All recommendations
are Category 2A unless otherwisespecified.
ANTICIPATORY EMESIS: The NCCN Guidelines™ are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches totreatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individualclinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes norepresentations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. All recommendations are category 2A unless otherwise indicated.
The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
illustrations herein may not be reproduced in any form without the express written permission of NCCN. 2010.
Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011 Updates
Updates in Version 1.2011 of the NCCN Guidelines from Version 1.2010 include:
· Modified the second bullet, "Oral and intravenous antiemetic
· Footnote j added the statement: "If allergic to diphenhydramine, use
formulations have equivalent efficacy when used at the appropriate
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."
· Added a new bullet: "Lifestyle measures may help to alleviate
· Added "haloperidol 1-2 mg PO every 4-6 h prn" for low to minimal emetic
nausea/vomiting, such as eating small frequent meals, choice of foods,
amount of food consumed, and eating food at room temperature. A
dietary consult may also be useful.
· Changed the dose of haloperidol from 1-2 mg PO or IV to 0.5-2.0 mg PO or
See NCI's "Eating Problems and Ways to Manage Them."
IV every 4-6 h.
· Added the following agents under high emetic risk category:
· Changed the title to "High Emetic Risk Intravenous Chemotherapy -
> Doxorubicin > 60 mg/m2
Acute and Delayed Emesis Prevention."
> Epirubicin > 90 mg/m2
· Modified recommendation for granisetron: "Granisetron 2 mg PO or 1
> Ifosfamide ³ 10 g/m2
mg PO bid or 0.01 mg/kg (max 1 mg) IV day 1 f or transdermal patch as
· Added the following agents under moderate emetic risk category:
3.1 mg/24 h patch (containing 34.3 mg granisetron total dose) applied
> Doxorubicin £ 60 mg/m2
approximately 24-48 h prior to first dose of chemotherapy, maximum
> Epirubicin < 90 mg/m2
duration of patch is 7 days."
· Fosaprepitant 150 mg IV added as a single dose regimen.
· Added the following agents under low emetic risk category:
· Added footnote f: "Some NCCN institutions use a 5-HT3 antagonist on
· Revised footnote e: "Order of listed antiemetics is alphabetical and does > Thiotepa
not reflect preference."
· Removed gemtuzumab ozogamicin from minimal emetic risk category.
· Footnote g is new to the page: "Use of steroids is contraindicated with · Added peginterferon to minimal emetic risk category.
drugs such as interleukin-2 (IL-2, aldesleukin) and interferon.
· The general principle of breakthrough treatment is to give an additional
· Footnote g is new to the page: "Use of steroids is contraindicated with
agent from a different drug class. No one drug class has been shown to
drugs such as interleukin-2 (IL-2, aldesleukin) and interferon."
be superior for the management of breakthrough emesis, and the choice
of agent should be based on assessment of the current prevention
· Following the pathway for low emetic risk intravenous chemotherapy -
strategies used. Some patients may require several agents utilizing
emesis prevention, changed the first bullet from "Repeat daily for
differing mechanisms of action.
fractionated doses of chemotherapy" to "Repeat daily for multiday
doses of chemotherapy."

· Footnote j added the statement "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."

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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
PRINCIPLES OF EMESIS CONTROL FOR THE CANCER PATIENT
· 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 antiemetic formulations have equivalent efficacy when used at the appropriate doses.
· Consider the toxicity of the specific antiemetic(s).
· Choice of antiemetic(s) used should be based on the emetic risk of the therapy, prior experience with antiemetics, as well as patient
· There are other potential causes of emesis in cancer patients.
These may include:
> Partial or complete bowel obstruction
> Vestibular dysfunction
> Brain metastases
> Electrolyte imbalance: hypercalcemia, hyperglycemia, hyponatremia
> Uremia
> Concomitant drug treatments including opiates
> Gastroparesis: tumor or chemotherapy (vincristine etc) induced or other causes (eg, diabetes).
F Anxiety
F Anticipatory nausea/vomiting
· For use of antiemetics for nausea/vomiting that are not related to radiation and/or chemotherapy,
· For multi-drug regimens, select antiemetic therapy based on drug with the highest emetic risk.
· Consider using an H2 blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea.
· Lifestyle measures may help to alleviate nausea/vomiting, such as eating small frequent meals, choice of foods, amount of food
consumed, and eating food at room temperature. A dietary consult may also be useful. See NCI's "Eating Problems and Ways to Manage
Them." http://www.cancer.gov/cancertopics/coping/eatinghints/page2#4

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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
HIGH EMETIC RISK INTRAVENOUS CHEMOTHERAPY - ACUTE and DELAYED EM ESIS PREVENTIONa,b,c
Start before chemotherapyc,d
· Serotonin (5-HT3) antagonist:
> Dolasetron 100 mg PO or 1.8 mg/kg IV or 100 mg IV day 1f
> Granisetron 2 mg PO or 1 mg PO bid or 0.01 mg/kg (max 1 mg) IV day 1f or transdermal patch as 3.1 mg/24 h patch
(containing 34.3 mg granisetron total dose) applied approximately 24-48 h prior to first dose of chemotherapy,
maximum duration of patch is 7 days
or

> Ondansetron 16-24 mg PO or 8-24 mg (max 32 mg/day) IV day 1f
> Palonosetron 0.25 mg IV day 1
· Steroid:g
> Dexamethasone 12 mg PO or IV day 1, 8 mg PO daily days 2-4
category 1
for combined

Neurokinin 1 antagonist
> Aprepitant 125 mg PO day 1, 80 mg PO daily days 2-3
> Fosaprepitant 115 mg IV on day 1 only, then aprepitant 80 mg PO daily days 2-3
> Fosaprepitant 150 mg IV day 1 only
· ± Lorazepam 0.5 -2 mg PO or IV or sublingual either every 4 hours or 6 hours day 1-4
· ± H2 blocker or proton pump inhibitor
a Data for post-cisplatin (³ 50 mg/m2) emesis prevention are category 1, others are category 2A.
eOrder of listed antiemetics is alphabetical and does not reflect preference.
c Antiemetic regimens should be chosen based on the drug with the highest emetic risk f Some NCCN institutions use a 5HT3 antagonist on days 2-3.
as well as patient specific risk factors.
g Use of steroids is contraindicated with drugs such as interleukin-2 (IL-2, aldesleukin) and interferon.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
MODERATE EMETIC RISK
CHEMOTHERAPY - EMESIS PREVENTIONb,c,h
DAYS 2 and 3
Start before chemotherapyc,d
· Serotonin (5-HT3) antagonist monotherapy:e
· Serotonin (5-HT3) antagonist:e
> Dolasetron 100 mg PO daily or 1.8 mg/kg or 100 mg IV
> Dolasetron 100 mg PO or 1.8 mg/kg or 100 mg IV (category 1)
> Granisetron 1-2 mg PO daily or 1 mg PO bid or 0.01 mg/kg
> Granisetron 2 mg PO or 1 mg PO bid or 0.01 mg/kg (max 1 mg) IV
(maximum 1 mg) IV
day 1 or transdermal patch as 3.1 mg/24 h patch (containing 34.3
mg granisetron total dose) applied approximately 24-48 h prior to
> Ondansetron 8 mg PO bid or 16 mg PO daily or 8 mg
first dose of chemotherapy, maximum duration of patch is 7 days
(maximum 32 mg/day) IV
> Ondansetron 16-24 mg PO or 8-12 mg (maximum 32 mg/day) IV
(category 1)
· Steroid monotherapy:
> Dexamethasone 8 mg PO or IV daily
> Palonosetron 0.25 mg IV (category 1) day 1 only
· Neurokinin 1 antagonist ± steroid (if NK-1 antagonist used
· Steroidg
on day 1)i
> Dexamethasone 12 mg PO or IV
> Aprepitant 80 mg PO ± dexamethasone
8 mg PO or IV daily
WITH / WITHOUT
· Neurokinin 1 antagonist (for selected patients, where appropriate)i
· ± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4
> Aprepitant 125 mg PO
or every 6 h prn
· ± H2 blocker or proton pump inhibitor
> Fosaprepitant 115 mg IV day 1 only
· ± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 or every gUse of steroids is contraindicated with drugs such as interleukin-2 (IL-2,
aldesleukin) and interferon.
± H2 blocker or proton pump inhibitor
Data for post-carboplatin ³ 300 mg/m , cyclophosphamide ³ 600-1000 mg/m , doxorubicin ³ 50 mg/m emesis prevention are category 1.
iAs per high emetic risk prevention, aprepitant should be added (to dexamethasone cAntiemetic regimens should be chosen based on the drug with the highest emetic and a 5-HT3 antagonist regimen) for select patients receiving other risk as well as patient specific risk factors.
chemotherapies of moderate emetic risk (for example, carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan or methotrexate)eOrder of listed antiemetics is alphabetical and does not does not reflect preference.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
LOW AND MINIMAL EMETIC RISK INTRAVENOUS CHEMOTHERAPY - EMESIS PREVENTIONc,d,k
Start before chemotherapyc,d
· Repeat daily for multiday doses of chemotherapyd
> Dexamethasone 12 mg PO or IV daily
> Metoclopramide 10-40 mg PO or IV and then either every 4 or every 6 h prnj
> Prochlorperazine 10 mg PO or IV and then every 4 or every 6 h prnj
· ± Lorazepam, 0.5-2 mg PO or IV either every 4 or every 6 h prn
· ± H2 blocker or proton pump inhibitor
No routine
cAntiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient specific risk factors.
j Monitor 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.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
ORAL CHEMOTHERAPY - EM ESIS PREVENTIONc,d,l,m
Start before chemotherapy and continue daily
·
Serotonin 5-HT3 antagonist d
> Dolasetron 100 mg PO daily
> Granisetron 2 mg PO daily or 1 mg PO bid
emetic risk
> Ondansetron 16-24 mg PO daily
· ± Lorazepam 0.5-2 mg PO or sublingual every 4 or every 6 h prn
· ± H2 blocker or proton pump inhibitor
Start before chemotherapy and continue
daily

> Metoclopramide 10-40 mg PO and then
every 4 or every 6 h prnj
> Prochlorperazine 10 mg PO and then
recommend any of
every 4 or every 6 h prn
emetic risk
> Haloperidol 1-2 mg PO every 4 or every
the oral 5-HT3
· ± Lorazepam 0.5-2 mg PO every 4 or
every 6 h prn
· ± H2 blocker or proton pump inhibitor
cAntiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient specific risk factors.
Order of listed antiemetics is alphabetical and does not reflect preference.
j Monitor 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.
m These antiemetic recommendations apply to oral chemotherapy only. When combined with IV agents in a combination chemotherapy regimen, the antiemetic recommendations for the agent with the highest level of emetogenicity should be followed. If multiple oral agents are combined, emetic risk may increase and requireprophylaxis.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
BREAKTHROUGH TREATMENT FOR CHEMOTHERAPY-INDUCED NAUSEA/VOMITINGd,n
RESPONSE TO
General principle of breakthrough treatment is to add one agent
from a different drug class prn to the current regimene
· Antipsychotic:
> Olanzapine 2.5-5 mg PO bid (category 2B)o
> Lorazepam 0.5-2 mg PO or IV either every 4 or every 6 h
Nausea and
Dronabinol 5-10 mg PO either every 3 or every 6 h
a schedule, not
> Nabilone 1-2 mg PO bid
> Metoclopramide 10-40 mg PO or IV either every 4 or every 6 hj
> Haloperidol 0.5 -2 mg PO or IV every 4-6 hj
to higher level
> Prochlorperazine 25 mg supp pr every 12 h or 10 mg PO or IV
for next cycle
every 4 or every 6 hj
Promethazine 12.5-25 mg PO or IV central line only every 4 hj
Serotonin 5-HT3 antagonists
> Dolasetron 100 mg PO daily or 1.8 mg/kg IV or 100 mg IV
to a different
> 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
e Order of listed antiemetics is alphabetical and does not reflect preference.
j Monitor 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.
o See blackbox warning/label indication regarding type II diabetes, hyperglycemia, and death in elderly dementia patients.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
EMETOGENIC POTENTIAL OF INTRAVENOUS ANTINEOPLASTIC AGENTS
High emetic risk
· AC combination defined as either doxorubicin
· Doxorubicin > 60 mg/m2
(> 90 % frequency of emesis)p,q
or epirubicin with cyclophosphamideq
· Epirubicin > 90 mg/m2
· Carmustine > 250 mg/m2
· Ifosfamide 10 g/m2
· Cisplatin ³ 50 mg/m2
· Cyclophosphamide > 1,500 mg/m2
Moderate emetic risk
· Aldesleukin > 12-15 million international units/m
· Epirubicin £ 90 mg/m
(30- 90 % frequency of emesis)p,r
· Amifostine > 300 mg/m2
· Ifosfamider < 10 g/m2
· Arsenic trioxide
· Interferon alfa ³ 10 million international units/m2
· Melphalan
· Busulfan
· Methotrexater ³ 250 mg/m2
· Carmustiner £ 250 mg/m2
· Cisplatinr < 50 mg/m2
· Cyclophosphamide £ 1,500 mg/m2
· Cytarabine > 200 mg/m2
· Doxorubicinr £ 60 mg/m2
Adapted with permission from:Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15: 103-109.
Grunberg SM, Osoba D, Hesketh PJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity---an update. Support Care Cancer 2005;13:80-84.
Epub 2004 Dec 14.
p Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxisq Continuous infusion may make this agent less emetogenic.
r These agents may be highly emetogenic in certain patients.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
EMETOGENIC POTENTIAL OF INTRAVENOUS ANTINEOPLASTIC AGENTS
· Amifostine £ 300 mg
Low emetic risk
· Methotrexate > 50 mg/m2 < 250 mg/m
· Aldesleukin £ 12 million international units/m2
(10-30 % frequency of emesis)p
· Mitomycin
· Cytarabine (low dose) 100-200 mg/m2
· Docetaxel
· Doxorubicin (liposomal)
· Etoposide
· Thiotepa
· Interferon alfa > 5 < 10 million international units/m2
· Topotecan
· Interferon alpha £ 5 million international units/m2
Minimal emetic risk
· Methotrexate £ 50 mg/m2
(< 10 % frequency of emesis)p
· Bleomycin
· Cetuximab
· Rituximab
· Cytarabine < 100 mg/m2
· Denileukin diftitox
Adapted with permission from:Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15: 103-109.
Grunberg SM, Osoba D, Hesketh PJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity---an update. Support Care Cancer 2005;13:80-84.
Epub 2004 Dec 14.
p Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxis.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
EMETOGENIC POTENTIAL OF ORAL ANTINEOPLASTIC AGENTS
Moderate to High
Busulfan ( 4 mg/day)
Cyclophosphamide ( 100 mg/m /day)
· Etoposide
· Lomustine (single day)
· Temozolomide (> 75 mg/m /day)
Minimal to Low
· Busulfan (< 4 mg/day)
· Melphalan
· Cyclophosphamide (< 100 mg/m /day)
· Nilotinib
· Dasatinib
· Pazopanib
· Erlotinib
· Sorafenib
· Sunitinib
· Temozolomide (£ 75 mg/m /day)
· Gefitinib
· Imatinib
· Topotecan
· Lapatinib
· Tretinoin
Adapted with permission from:Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997;15: 103-109.
Grunberg SM, Osoba D, Hesketh PJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity---an update. Support Care Cancer 2005;13:80-84.
Epub 2004 Dec 14.
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
TYPE OF RADIATION THERAPY
Start pretreatment for each day of RT treatment:
· Ondansetron 8 mg PO bid
RT - upper abdomen /
Granisetron 2 mg PO daily
· ± Dexamethasone 4 mg PO daily
Start pretreatment for each day of RT treatment:
·
Ondansetron 8 mg PO bid-tid
Total body irradiation
Granisetron 2 mg PO daily,
· ± Dexamethasone 4 mg PO daily
Chemotherapy and RT
See emesis prevention for chemotherapy-induced nausea/vomiting
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.

Version 1.2011, 11/30/2010 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Printed by Daniel Lim on 1/13/2011 2:06:53 AM. For personal use only. Not approved for distribution. Copyright 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
NCCN Guidelines™ Version 1.2011
Prevention:
· Use optimal antiemetic therapy during every cycle of treatment
· Hypnosis/guided imagery
· Music therapy
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

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.

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ersion 1.201
PRINCIPLES OF MANAGING MULTIDAY EMETOGENIC CHEMOTHERAPY REGIMENS
· Patients receiving multi-day chemotherapy are at risk for both acute and delayed nausea/vomiting based upon the emetogenic potential of
the individual chemotherapy agents and their sequence. It is therefore difficult to recommend a specific antiemetic 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

he period of risk for delayed emesis also depends on the specific regimen and the
chemotherapy administration has concluded, t
emetogenic potential of the last chemotherapy agent administered in the regimen.

· Examples illustrating the above include BEP (bleomycin 30 units IV weekly, etoposide 100 mg/m2 IV days 1-5 and cisplatin 20 mg/m2 IV days
1-5) versus ASHAP (doxorubicin 25 mg/m2 IV day 1, methylprednisolone 500 mg/day IV days 1-5, cisplatin 25 mg/m2 IV continuous infusion
days 1-4 followed by cytarabine 2000 mg/m2 on day 5). BEP is moderately emetogenic with risk for emesis on days 1-8) whereas ASHAP is
moderately emetogenic on days 1-4 but becomes highly emetogenic on day 5 due to the administration of high-dose cytarabine). Risk for
acute and delayed emesis for ASHAP may last up to 10 days.

Accordingly, the panel recommends the following as general principles:
· Dexamethasone should be administered once daily (either orally or intravenously) for moderately or highly emetogenic chemotherapy and
for 2-3 days after chemotherapy for regimens that are likely to cause significant delayed-emesis Dexamethasone
should not be added when the chemotherapy regimen already includes a corticosteroid (as in ASHAP illustrated above).

· Intravenous palonosetron may be used prior to the start of a three day chemotherapy regimen instead of multiple daily doses of oral or
intravenous 5-HT3 receptor antagonists
dose ranging Phase II trial where up to 30 times the FDA approved dose (90 mcg/kg) was administered and the 3 Phase III trials that
evaluated palonosetron 0.75 mg as a single fixed dose. Compared to the approved dose of palonosetron 0.25 mg, these higher doses were
not associated with significantly different grades or durations of adverse events. In terms of efficacy, need for repeat dosing with
palonosetron, either daily or less frequently, in the setting of multiday chemotherapy is not yet known.

· Aprepitant may be used for multiday chemotherapy regimens likely to be highly emetogenic and associated with significant risk for delayed
Category 1 evidence is available for single day chemotherapy regimens only, and aprepitant should be
administered 125 mg orally 1 hour prior to chemotherapy on day one, 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. Based upon
Phase II data, aprepitant 80 mg may be safely administered 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. Note that fosaprepitant dimeglumine (115 mg) may be
substituted for aprepitant (125 mg) on day 1 only.

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 clinica

Clinical T
l trials is especially encouraged.
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NCCN Guidelines™ Version 1.2011
PRINCIPLES FOR MANAGING BREAKTHROUGH EMESIS
· Breakthrough emesis presents a difficult situation as correction of refractory ongoing nausea/vomiting is often challenging to reverse. It is
generally far easier to prevent nausea/vomiting than 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 shown
to 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 fluid repletion, simultaneously checking and correcting any possible electrolyte abnormalities.
· Prior to administering the next cycle of chemotherapy the patient should be reassessed, with attention to various possible non-
chemotherapy related reasons for breakthrough emesis with the current cycle:
> Brain metastases
> Electrolyte abnormalities
> Tumor infiltration of the bowel or other gastrointestinal abnormality
> Other comorbidities
· Prior to the next cycle of chemotherapy, reassess both the Day 1 and post-chemo antiemetic regimen which did not protect the patient during
the present cycle and consider alternatives: (Suggestions are not in order of preference)
> Addition of aprepitant if not previously included
> Add other concomitant antiemetics, eg, dopamine antagonists (metoclopramide
> Possibly adjusting 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 classified (eg, Hesketh method)
> Possibly switching to a different 5-HT3 although not necessarily likely to be effective, anecdotal and limited investigational trial data
suggest it may sometimes be efficacious.
> If the goal of chemotherapy is non-curative, consider other appropriate regimens, if any, which might be less emetogenic.
> Addition of an anxiolytic agent in combination with the antiemetic agents may be beneficial.
· If patient has dyspepsia consider antacid therapy (H2 blocker or proton pump inhibitor).
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.

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Discussion This discussion is being updated to correspond with the
individual patient variability (e.g., age, sex, prior chemotherapy, history newly updated algorithm. Last updated 04/12/10 of alcohol use).5, 6 Approximately 70% to 80% of all cancer patients receiving chemotherapy experience nausea and/or vomiting,7, 8 NCCN Categories of Evidence and Consensus
whereas 10% to 44% experience anticipatory nausea and/or Category 1: The recommendation is based on high-level evidence
vomiting.9-12 Patients often experience more nausea than vomiting.13 (e.g. randomized controlled trials) and there is uniform NCCN Pathophysiology of Emesis
Vomiting results from stimulation of a multistep reflex pathway Category 2A: The recommendation is based on lower-level evidence
controlled by the brain.5 Vomiting is triggered by afferent impulses to and there is uniform NCCN consensus. the vomiting center (located in the medulla) from the chemoreceptor Category 2B: The recommendation is based on lower-level evidence
trigger zone, pharynx and gastrointestinal (GI) tract (via vagal afferent and there is nonuniform NCCN consensus (but no major fibers), and cerebral cortex. Vomiting occurs when efferent impulses are sent from the vomiting center to the salivation center, abdominal muscles, respiratory center, and cranial nerves.14 Category 3: The recommendation is based on any level of evidence
but reflects major disagreement. The chemoreceptor trigger zone, vomiting center, and GI tract have All recommendations are category 2A unless otherwise noted.
many neurotransmitter receptors. Activation of these receptors by chemotherapeutic agents or their metabolites may be responsible for Overview
chemotherapy-induced emesis. The principal neuroreceptors involved in the emetic response are the serotonin (5-hydroxytryptamine [5-HT3]) Chemotherapy-induced vomiting (emesis) and nausea can significantly and dopamine receptors.15, 16 Other neuroreceptors involved in emesis affect a patient's quality of life, leading to poor compliance with further include acetylcholine, corticosteroid, histamine, cannabinoid, opiate, chemotherapy treatment. In addition, nausea and vomiting can result in and neurokinin-1 (NK-1) receptors, which are located in the vomiting metabolic imbalances, degeneration of self-care and functional ability, and vestibular centers of the brain.17 nutrient depletion, anorexia, decline of the patient's performance status and mental status, wound dehiscence, esophageal tears, and Antiemetic agents can block different neuronal pathways, exert their withdrawal from potentially useful or curative anticancer treatment.1-4 effects at different points during the course of emesis, or behave synergistically with other antiemetic agents to potentiate an antiemetic The incidence and severity of nausea and/or vomiting in patients effect. When used at a certain concentration, each antiemetic agent receiving chemotherapy are affected by numerous factors, including: predominantly blocks one receptor type. A final common pathway for (1) the specific chemotherapeutic agents used; (2) dosage of the emesis has yet to be identified. Therefore, no single agent can be agents; (3) schedule and route of administration of the agents; and (4) Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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Antiemesis
expected to provide complete protection from the various emetic chemotherapy and, overall, have poorer emesis control than older phases of chemotherapy. patients.22 Breakthrough emesis refers to vomiting that occurs despite prophylactic treatment and/or requires "rescue" with antiemetic agents. Types of Nausea and/or Vomiting
Refractory emesis refers to emesis that occurs during subsequent Chemotherapy-Induced Nausea and/or Vomiting
treatment cycles when antiemetic prophylaxis and/or rescue have failed Nausea and/or vomiting induced by chemotherapy is commonly in earlier cycles. classified as acute, delayed, anticipatory, breakthrough, or refractory. Radiation-Induced Nausea and/or Vomiting
Acute-onset nausea and/or vomiting usually occurs within a few minutes to several hours after drug administration and commonly Patients receiving whole body or upper abdominal radiation therapy resolves within the first 24 hours. The intensity of acute-onset emesis have the greatest likelihood of developing nausea and/or vomiting.23, 24 generally peaks after 5 to 6 hours. The occurrence of acute emesis is The GI tract (specifically, the small intestine) contains rapidly dividing influenced by the patient's age and gender (females and younger cells that are particularly sensitive to radiation. In addition, the potential patients [age < 50 years] are more prone to emesis), environment in for nausea and/or vomiting increases with larger daily fractional doses which chemotherapy is administered, whether the patient has a history of radiotherapy, larger total doses, and larger amounts of irradiated of chronic alcoholism (which decreases the incidence of emesis) or tissue. Total body irradiation, when given before bone marrow motion sickness, previous episodes of nausea and vomiting, dosage of transplantation, also commonly induces nausea and/or vomiting.24, 25 the emetogenic agent, and efficacy of the antiemetic regimen.18, 19 Emetogenicity of Chemotherapy
Delayed-onset nausea and/or vomiting develops in patients more than The frequency of chemotherapy-induced emesis depends primarily on 24 hours after chemotherapy administration.18, 19 It occurs commonly the emetogenic potential of the specific chemotherapeutic agents used. with the administration of cisplatin, carboplatin, cyclophosphamide, Several classifications have been developed to define the and/or doxorubicin. For cisplatin, emesis reaches its maximal intensity emetogenicity of chemotherapy; however, none has been universally 48 to 72 hours after administration and can last 6 to 7 days. accepted.14, 26-29 Anticipatory nausea and/or vomiting occurs before patients receive their Hesketh and colleagues developed a classification of the acute next chemotherapy treatment. Because it is a conditioned response, emetogenicity of anticancer chemotherapeutic agents and developed anticipatory emesis can occur only after a negative past experience an algorithm to define the emetogenicity of combination with chemotherapy. The incidence of anticipatory nausea and/or chemotherapeutic regimens.30 The classification was updated by vomiting ranges from 18% to 57%, and nausea is more common than Grunberg and colleagues; it divides chemotherapeutic agents into 4 vomiting.20, 21 Younger patients may be more susceptible to anticipatory levels according to the percentage of patients not receiving antiemetic nausea and vomiting, because they generally receive more aggressive prophylaxis who experience acute emesis.31 This classification, which is Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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updated each year with recently introduced drugs, is used in these term (e.g., imatinib). Antiemetic agents can be administered by the oral, NCCN practice guidelines. Panel members from all of the published rectal, IV, intramuscular, or transdermal route. When compared with antiemetic treatment guidelines met to prepare a single consensus other routes of administration, oral formulations of antiemetic agents document. Although this process is ongoing, the consensus guidelines are equally effective, safe, more convenient, and less costly. For have been published.32 NCCN guidelines currently outline treatment patients unable to swallow or digest tablets because of emesis, IV using 4 categories of emetogenic potential for intravenous (IV), which antiemetics are required. In selected patients who are unable to correspond to the Grunberg classification as follows: swallow, transdermal antiemetics may be of value. Although studies may show drugs to be equally effective on a population basis, individual  High emetic risk—90% or more of patients experience acute emesis patients may respond differently. Therefore, some drug options may be  Moderate emetic risk—30% to 90% of patients experience acute based on a patient's individual experience.  Low emetic risk—10% to 30% of patients experience acute emesis Serotonin (5-HT3) Receptor Antagonists
 Minimal emetic risk—fewer than 10% of patients experience acute The development of the 5-HT3–receptor antagonists (i.e., dolasetron mesylate, granisetron, ondansetron, palonosetron) represents a significant advance in antiemetic therapy.33-35 All of these agents have In addition, the NCCN guidelines attempt to define antiemetic regimens been shown to be effective in controlling the acute nausea and/or for particular chemotherapy drugs that cover the entire duration of time vomiting associated with cancer chemotherapy.35-49 a patient is at risk for nausea and vomiting. Panel members were concerned that some patients may not receive adequate prophylaxis for Palonosetron is a 5-HT3 antagonist with an approximately 100-fold delayed emesis; therefore, the algorithms were revised for high and higher binding affinity for the 5-HT3 receptor compared to the other moderate emetogenic potential agents to incorporate a dosing schedule serotonin antagonists (i.e., ondansetron, granisetron, and dolasetron). It that covers both acute and delayed emesis into a single algorithm. has a half-life of approximately 40 hours, which is significantly longer Recently, NCCN panel members categorized the emetogenic potential than other commercially available 5-HT3 antagonists.35 Initial studies in of oral antineoplastic agents. patients receiving moderately emetogenic chemotherapy showed that a single IV dose of palonosetron was comparable to a single IV dose of Types of Antiemetic Therapies
dolasetron for the prevention of acute chemotherapy-induced nausea In general, to provide maximal protection against chemotherapy- and emesis; however, IV palonosetron was superior to dolasetron in induced emesis, antiemetic therapy should be initiated before preventing delayed emesis.50 The safety and side-effect profiles of chemotherapy. The antiemetic therapy should also be continued for the palonosetron were indistinguishable from the control 5-HT3 antagonists same length of time as the duration of the emetic activity of the (ondansetron and dolasetron) using data submitted to the Food and chemotherapeutic agent being used. However, daily use of antiemetics Drug Administration (FDA). Intravenous palonosetron is FDA approved is not recommended for some therapeutic agents that are taken long as a single dose on day 1; it is recommended (category 1) for acute Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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and delayed emesis prevention when using moderate emetic risk However, IV palonosetron is effective for preventing both delayed and acute emesis. A meta-analysis of randomized controlled trials found that adding a 5-HT3 antagonist to dexamethasone did not improve the Intravenous palonosetron is superior to other 5-HT3 antagonists for antiemetic effect of dexamethasone for preventing delayed emesis.73 preventing delayed nausea.51 Repeat dosing of palonosetron in the Another study found that 5-HT3 antagonists (except palonosetron, days after chemotherapy (i.e., days 2 or 3) is likely to be safe. However, which was not studied) were not more effective than prochlorperazine in the setting of multi-day chemotherapy, need for repeat dosing with for preventing delayed emesis.13 palonosetron is not yet known (see "Managing Multi-day Emetogenic Chemotherapy Regimens"). Neurokinin-1–Receptor Antagonist
Aprepitant selectively blocks the binding of substance P at the NK-1 Many of the 5-HT3 antagonists can be delivered orally or intravenously. receptor in the central nervous system. Thus, aprepitant provides a In addition, the FDA has approved the use of a granisetron transdermal different and complementary mechanism of action to all other system for chemotherapy-induced nausea and vomiting. The patch commercially available antiemetics. Aprepitant has been shown to containing 34.3 mg of granisetron is applied approximately 24 to 48 augment the antiemetic activity of the 5-HT3–receptor antagonists and hours before the first dose of chemotherapy; the maximum duration of the corticosteroid dexamethasone to inhibit both acute and delayed the patch is 7 days. A phase III randomized study compared the patch cisplatin-induced emesis. The FDA has approved the use of aprepitant to oral granisetron in patients receiving either highly emetogenic or for preventing emesis in patients receiving moderately emetogenic moderately emetogenic chemotherapy. The patch proved non-inferior chemotherapy. An IV version of aprepitant (fosaprepitant dimeglumine), to repeat dosing of the oral antiemetic granisetron over 3 to 5 days.52, 53 which can be given on day 1 only, is also approved by the FDA. IV Many clinical trials directly comparing ondansetron, granisetron, fosaprepitant is given 30 minutes before chemotherapy on day 1 dolasetron mesylate, and palonosetron have been conducted. These only, per the package insert. trials have used various doses, routes, and schedules of When combined with 5-HT3 antagonists and dexamethasone on day 1 administration.50, 54-71 Studies have demonstrated that the 5-HT3 before cisplatin-based highly emetogenic chemotherapy and continued antagonists are equally effective and have mild, infrequent side effects. orally along with dexamethasone on days 2 and 3 after chemotherapy, A meta-analysis found no difference in efficacy between ondansetron, aprepitant significantly improved control of acute and delayed granisetron, and dolasetron mesylate.72 The addition of dexamethasone chemotherapy-induced nausea and emesis.74, 75 The oral doses of improves the efficacy of the antiemetic regimen containing 5-HT3 aprepitant are 125 mg on day 1 (before chemotherapy) and then 80 mg on days 2 and 3 (after chemotherapy).76 There are no studies showing Ondansetron, granisetron, and dolasetron are effective in preventing efficacy or safety of chronic dosing with aprepitant. It is possible that acute emesis but appear to be less effective for delayed emesis. the drug-drug interaction profile may change with chronic dosing. Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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A randomized phase III study (866 patients) showed that an aprepitant forms because of first-pass metabolism. Patients should not take regimen is better than a standard regimen for preventing vomiting in aprepitant with pimozide, terfenadine, astemizole, or cisapride; these patients receiving moderately emetogenic chemotherapy (non-cisplatin combinations are contraindicated, because they may cause "serious or based) during 120 hours after initiation of chemotherapy (complete life-threatening reactions" (see the aprepitant package insert). response, 50.8% versus 42.5%, P=.015); however, 40% of patients (receiving either regimen) still had significant nausea.77, 78 The Chemotherapeutic agents known to be metabolized by CYP3A4 include aprepitant regimen included aprepitant, ondansetron, and docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, dexamethasone; the standard regimen included ondansetron and vinorelbine, vinblastine, and vincristine. In clinical trials, aprepitant was dexamethasone. An analysis of 2 phase III randomized trials found that used concurrently with etoposide, vinorelbine, or paclitaxel; although an aprepitant regimen is useful for patients receiving moderately chemotherapy doses were not adjusted for potential drug interactions in emetogenic chemotherapy plus high-dose cisplatin.79 phase III trials, caution is urged when using any chemotherapeutic agent that is metabolized by CYP3A4. A meta-analysis (7 randomized controlled trials) in patients receiving highly emetogenic chemotherapy found that NK-1 receptor antagonists Aprepitant has been shown to interact with several used alone or with standard therapy for acute emesis were not better nonchemotherapeutic drugs (including warfarin, dexamethasone, than the control; however, for delayed emesis, NK-1 receptor methylprednisolone, oral contraceptives). Again, these interactions are antagonists were better than the control.80 A phase II study (58 more significant with orally administered forms of these drugs than with patients) found that combining palonosetron, aprepitant, and IV forms because of first-pass metabolism. dexamethasone was useful for various chemotherapeutic regimens Induction of warfarin metabolism by aprepitant may lead to clinically (moderate to moderate-highly emetogenic); 78% of patients had a significant reductions in INR (international normalized ratio) values, complete response (no emetic episodes and no rescue medication).81 A particularly for patients on therapeutic (as compared to prophylactic) similar study in 40 patients with breast cancer also found that a single warfarin regimens. These changes, although brief in duration, may day regimen of palonosetron, aprepitant, and dexamethasone was require increased patient monitoring. effective; 76% of patients had a complete response.82 Aprepitant decreases the AUC for patients taking oral contraceptives; Drug Interactions
thus, other methods of birth control should be used during treatment Aprepitant is simultaneously a substrate, moderate inducer, and with aprepitant and for 1 month after the last dose of aprepitant (see moderate inhibitor of cytochrome P450 enzyme 3A4 (CYP3A4); package insert). aprepitant also induces CYP2C9.83 Thus, aprepitant can alter the metabolism of certain drugs and change their plasma concentrations Certain drugs can affect the AUCs of aprepitant. Concomitant (i.e., AUCs [area under the curve]). These interactions are more administration with CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, significant with orally administered forms of these drugs than with IV erythromycin) may lead to increased aprepitant AUCs, whereas Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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concomitant administration with CYP3A4 inducers (e.g., Principles of Emesis Control
carbamazepine, rifampin, phenytoin) may lead to decreased levels of These principles are discussed in the algorithm.  The goal is to prevent nausea and/or vomiting. Other Non–5-HT3–Receptor Antagonist Antiemetics
 The risk of emesis and nausea for persons receiving chemotherapy Before the advent of the 5-HT3–receptor antagonists, the available of high and moderate emetogenic potential lasts at least 3 days for antiemetic agents included phenothiazines,84 substituted high and 2 days for moderate after the last dose of chemotherapy. benzamides,85, 86 antihistamines,87 butyrophenones,88 cortico- Patients need to be protected throughout the full period of risk. steroids,89-91 benzodiazepines,92, 93 and cannabinoids.94, 95 Most drugs  Oral and IV antiemetic formulations have equivalent efficacy. used to prevent chemotherapy-induced emesis are classified as  The toxicity of the specific antiemetic(s) should be considered. dopamine antagonists, serotonin antagonists, and other antagonists.  Antiemetic regimens should be chosen based on the drug with the Combination antiemetic therapy is more effective than single-agent highest emetic risk in the chemotherapy regimen, previous therapy. Olanzapine (thiobenzodiazepine) was found to be effective for experience with antiemetics, and patient-specific risk factors. acute and delayed emesis in a phase II trial in patients (n = 30) who received cyclophosphamide, doxorubicin, and/or cisplatin;96, 97 other In addition to emesis induced by chemotherapy, emesis in cancer studies have also showed the value of olanzapine for delayed and patients can also potentially be caused by: refractory emesis and nausea.98-101 However, olanzapine should be used with caution in elderly patients (see boxed warning/label indication Partial or complete bowel obstruction regarding death, type II diabetes, and hyperglycemia).102  Vestibular dysfunction  Brain metastases Treatment Issues
 Electrolyte imbalance: hypercalcemia, hyperglycemia, hyponatremia Selected issues that arose in the panel's deliberations on the guidelines are discussed in the following sections. As new data about the use of  Concomitant drug treatments, including opiates antiemetics in patients receiving chemotherapy become available,  Gastroparesis induced by a tumor or chemotherapy (i.e., vincristine) clinicians should consider these data when caring for such patients, or other causes (e.g., diabetes). even if the information has not been included in the guidelines. In  Psychophysiologic factors, including anxiety and anticipatory nausea contrast to other NCCN guidelines in which most of the recommendations are category 2A, many of the recommendations for  For use of antiemetics for nausea and vomiting that is not related to antiemetic management are classified as category 1, reflecting the large number of randomized controlled trials that have focused on antiemetic management. Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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 For multidrug regimens, select antiemetic therapy based on drug with with or without either an H2 blocker or a proton pump inhibitor (category the highest emetic risk.30, 31 1 for the combined regimen);24, 25, 74 note that the regimen and doses are often modified on days 2 to 4 after chemotherapy. Prevention of Acute Emesis
To prevent acute emesis, antiemetic therapy should start before the A recent randomized trial suggested that palonosetron is preferred for administration of chemotherapy and then should cover the first 24 high emetic risk chemotherapy in combination with dexamethasone.103 hours. For highly emetogenic IV drugs, the antiemetic regimens are However, this trial has been criticized because: 1) the control arm was described in the algorithm. For moderately emetogenic IV drugs, the not adequately dosed; thus, the trial "stacked the deck" in favor of regimens are described in the algorithm. For low and minimally palonosetron; 2) a larger non-FDA-approved dose of palonosetron was emetogenic IV drugs, the regimens are described in the algorithm. used; and 3) aprepitant was not used in this study. Therefore, the Emesis prevention for oral chemotherapeutic agents is described in the NCCN panel does not believe that palonosetron is preferred over the algorithm. This section discusses prechemotherapy and other 5-HT3 antagonists for high emetic risk chemotherapy. postchemotherapy emesis prevention rather than primary treatment. A Canadian meta-analysis suggests that it is not cost-effective to use 5-HT3 antagonists (i.e., ondansetron) on days 2 to 4 to prevent delayed The guidelines specify different prophylactic antiemetic regimens for emesis; however, ondansetron (when used alone) did protect against cancer patients receiving chemotherapy of different emetogenic delayed emesis in this meta-analysis.104 Palonosetron was not potential (i.e., high, moderate, low, minimal). Prophylactic antiemetics assessed in these studies. The NCCN panel recommends the use of should be administered before chemotherapy. The recommendations 5-HT3 antagonists as one of several options to prevent delayed emesis for prophylactic antiemetic treatment include drug dosages. The for moderately emetogenic agents. guidelines reflect accumulating experience with the 5-HT3 antagonists, The antiemetic regimen for moderately emetogenic IV drugs on day 1 demonstrating their effectiveness in a range of doses. Unless indicated, includes dexamethasone and a 5-HT3 antagonist with or without the order of listed antiemetics in the algorithm does not reflect lorazepam and/or either an H2 blocker or a proton pump inhibitor.5, 78 Aprepitant (or fosaprepitant) should be added (to dexamethasone and a Highly emetogenic IV drugs include carmustine > 250 mg/m2, cisplatin 5-HT3 antagonist) for select patients receiving other chemotherapies of at 50 mg/m2 or more, cyclophosphamide > 1500 mg/m2, dacarbazine, moderate emetic risk (e.g., carboplatin, cisplatin, doxorubicin, mechlorethamine, streptozocin, or anthracycline plus epirubicin, ifosfamide, irinotecan, or methotrexate), because these cyclophosphamide (AC) combinations (doxorubicin or epirubicin with agents are more emetogenic than the other moderately emetogenic cyclophosphamide). The antiemetic regimen for these highly agents.25, 30 Any one of the 5-HT3 antagonists can be used, because emetogenic drugs on day 1 includes aprepitant (or fosaprepitant), they are all category 1 for day 1. Note that IV fosaprepitant may be dexamethasone, and a 5-HT3 antagonist with or without lorazepam and substituted for oral aprepitant on day 1 only. Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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Antiemesis
The antiemetic regimen for low emetogenic IV drugs includes Postchemotherapy/Delayed Emesis Prevention
non-5-HT3 antagonists, such as dexamethasone, prochlorperazine, or The best management for delayed emesis is prevention.105 For metoclopramide, with or without lorazepam and/or either an H2 blocker chemotherapy involving agents with high emetogenic potential, the or a proton pump inhibitor. When using prochlorperazine or prophylactic treatment (i.e., dexamethasone and aprepitant) is metoclopramide, patients should be monitored for dystonic reactions. continued through the period when delayed emesis may occur. Using Diphenhydramine (25-50 mg PO or IV either every 4 or every 6 hours) this strategy, prophylaxis continues for 2 to 4 days after completion of a can be used for dystonic reactions. chemotherapy cycle. However, 5-HT3 antagonists are given on day 1 For IV regimens with high emetogenic potential, aprepitant is used at a oral dosage of 125 mg on day 1 and then 80 mg on days 2 and 3. For drugs with moderate emetogenic potential, postchemotherapy When given with aprepitant, dexamethasone is used at a dosage of 12 prevention depends on what antiemetics were used before mg on day 1; the dose can be oral or IV. All four 5-HT3–receptor chemotherapy. For example, palonosetron (category 1) is only antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron) administered on day 1.54 If aprepitant or fosaprepitant was used on day are considered to have similar effectiveness for control of acute emesis. 1, then aprepitant is continued on days 2 and 3. If appropriate, lorazepam (0.5-2 mg either every 4 or every 6 hours on days 1-4; either oral, IV, or sublingual) may be used with each of these Note that the NCCN antiemetic regimens differ on days 2 to 3.24, 25, 105 regimens (i.e., high, moderate, or low). There are 4 possible regimens on days 2-3 (lorazepam and/or either an H2 blocker or a proton pump inhibitor may be added to each of these The emetogenic potential of oral chemotherapeutic agents is shown in regimens) including: 1) aprepitant and dexamethasone; 2) aprepitant; the algorithm. Antiemetic prophylaxis is recommended for the following 3) dexamethasone; or 4) 5-HT3 antagonist, such as ondansetron, oral agents: altretamine, busulfan (4 mg/d or more), cyclophosphamide granisetron, or dolasetron.105 It is important to note that the doses of (100 mg/m2/day or more), estramustine, etoposide, lomustine (single both aprepitant (80 mg PO) and dexamethasone (8 mg PO or IV) are day), procarbazine, and temozolomide (75 mg/m2/day or more). decreased when used on days 2-3 (when compared with the doses Prophylaxis uses oral 5-HT3 antagonists (such as dolasetron, given on day 1). Note that palonosetron is not given on days 2-3. granisetron, or ondansetron) with or without lorazepam and/or either an H2 blocker or a proton pump inhibitor. If routine prophylaxis is not The NCCN, MASCC (Multinational Association of Supportive Care in recommended, then either metoclopramide or prochlorperazine may be Cancer), and ASCO (American Society of Clinical Oncology) guidelines given before chemotherapy is started and then on an as needed basis all recommend using aprepitant to prevent delayed nausea and/or only (i.e., PRN) with or without lorazepam and/or either an H2 blocker vomiting when giving AC regimens.24, 25 Several randomized trials have or a proton pump inhibitor. shown that dexamethasone is efficacious for preventing delayed emesis; however, only one trial found that use of a 5-HT3 antagonist is effective.105 The MASCC and NCCN (but not ASCO) guidelines also Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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recommend using dexamethasone for preventing delayed emesis when chemotherapy, the antiemetic regimen (both the day 1 and giving AC regimens.105 postchemotherapeutic) that did not protect the patient during the present cycle should be assessed and alternatives should be Breakthrough Treatment
considered. Consider using antacid therapy (e.g., proton pump Breakthrough emesis presents a difficult situation, because refractory inhibitors, H2 blockers) if patients have dyspepsia, because patients ongoing nausea and/or vomiting is often challenging to reverse. sometimes have difficulty discriminating heartburn from nausea. Generally, it is much easier to prevent nausea and/or vomiting than to treat it. Thus, routine around-the-clock administration of antiemetics Radiation-Induced Nausea and/or Vomiting
should be strongly considered to prevent emesis, rather than PRN (as Prophylaxis for radiation-induced nausea and/or vomiting is based on required) dosing. The general principle of breakthrough treatment is to the site of radiation and whether it is combined with chemotherapy.109 give an additional agent as needed from a different drug class.24 When radiation is combined with chemotherapy, prophylaxis is dictated However, no one treatment is better than another for managing by the emetogenic potential of the chemotherapy regimen. breakthrough emesis.106 Some patients may require several agents using different mechanisms of action. The oral route is not likely to be Radiation to the upper abdomen may be treated with oral ondansetron feasible because of ongoing vomiting; therefore, rectal or IV therapy is (8 mg 2 times daily), with or without oral dexamethasone, based on the often required. Nasal sprays (e.g., metoclopramide) might be useful for results of a randomized study comparing oral ondansetron with placebo treatment of breakthrough emesis, because they provide acute delivery in patients receiving daily fractionated radiotherapy including the of agents.107, 108 Multiple concurrent agents, perhaps in alternating abdomen. In this study, 67% of patients given ondansetron had schedules or by alternating routes, may be necessary. complete control of emesis compared with 45% of patients who received placebo.110 A study showed that the addition of oral Dopamine antagonists (e.g., metoclopramide), haloperidol, dexamethasone (4 mg daily) to the ondansetron regimen decreases corticosteroids, and agents such as lorazepam may be required. emesis and nausea, although the effect is modest.111 Another option is Nabilone (which is a cannabinoid) is approved by the FDA for nausea oral granisetron (2 mg every day) with or without oral dexamethasone. and vomiting in patients who have not responded to conventional antiemetic agents. Adequate hydration or fluid repletion should be Total body irradiation may be treated with either ondansetron (8 mg 2 to ensured, and any possible electrolyte abnormalities should be 3 times daily) or granisetron; either agent can be given with or without assessed and corrected. Before administering the next cycle of oral dexamethasone (2 mg 3 times daily).111 The dose of granisetron is chemotherapy, the patient should be reassessed with attention to either 2 mg oral every day or 3 mg IV every day112, 113 (category 2B various possible nonchemotherapy-related reasons for breakthrough recommendation, because this dose of granisetron is higher than the emesis with the current cycle (i.e., brain metastases, electrolyte dose typically used). No prophylaxis is recommended for patients abnormalities, tumor infiltration of the bowel or other GI abnormality, receiving irradiation to other sites. and other comorbidities. In addition, before the next cycle of Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, 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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Antiemesis
Treatment of breakthrough radiation-induced emesis is similar to difficult to recommend a specific antiemetic regimen for each day, chemotherapy-induced emesis. Patients who do not receive primary especially because acute and delayed emesis may overlap after the prophylaxis and experience breakthrough nausea and/or vomiting may initial day of chemotherapy until the last day of chemotherapy. The be treated with ondansetron, similar to primary prophylaxis. period of risk for delayed emesis after chemotherapy administration has concluded also depends on the specific regimen and the emetogenic Anticipatory Nausea and/or Vomiting
potential of the last chemotherapy agent administered in the regimen. The most effective way to treat anticipatory nausea and/or vomiting is For multi-drug regimens, antiemetic therapy should be selected based to prevent it by using optimal antiemetic therapy during every cycle of on the drug with the highest emetic risk. General principles for treatment.24, 114 Behavioral therapy has been used in patients with managing multi-day emetogenic chemotherapy regimens anticipatory nausea and/or vomiting.115-120 Systematic desensitization recommended by the panel are described in the algorithm. may also be helpful.116 Hypnosis with guided imagery is another behavioral technique that has shown some success in treating this Dexamethasone should be administered once daily either orally or intravenously for every day of moderately or highly emetogenic chemotherapy and for 2-3 days after chemotherapy for regimens that The antianxiety agents, lorazepam and alprazolam, have been are likely to cause significant delayed emesis. However, combined with antiemetics for anticipatory nausea and/or dexamethasone should not be added when the chemotherapy regimen vomiting.114,121, 122 The usual starting dose of alprazolam for anxiety is already includes a corticosteroid. 0.25 to 0.5 mg orally A 5-HT3 receptor antagonist should be administered each day before 3 times daily, beginning on the night before treatment. In elderly the first dose of moderately or highly-emetogenic chemotherapy. patients, patients with debilitating disease, and patients with advanced Intravenous palonosetron may be used before the start of a 3-day liver disease, the usual starting dose of alprazolam is 0.25 mg orally 2 chemotherapy regimen instead of multiple daily doses of oral or or 3 times daily for treatment of anxiety. This dose may be gradually intravenous 5-HT3 receptor antagonists.127, 128 Repeat dosing of increased if needed. Note that the elderly are especially sensitive to the palonosetron 0.25 mg IV is likely to be safe, based upon the dose effects of benzodiazepines. The dose should be gradually reduced ranging phase II trial where up to 30 times the FDA-approved dose (90 when decreasing or discontinuing alprazolam therapy. mcg/kg) was administered and the 3 phase III trials that evaluated palonosetron 0.75 mg as a single fixed dose.50, 54, 129, 130 Compared to Managing Multi-Day Emetogenic Chemotherapy
the approved dose of palonosetron of 0.25 mg, these higher doses Regimens
were not associated with significantly different grades or durations of Patients receiving multi-day chemotherapy are at risk for both acute adverse events. Of note, patients receiving highly emetogenic multi-day and delayed nausea and vomiting based on the emetogenic potential of cisplatin-based chemotherapy for testicular cancer received multiple- the individual chemotherapy agents and their sequence.24, 75, 123-126 It is day dosing of palonosetron and dexamethasone, which prevented Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-10
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Antiemesis
nausea and emesis.131 In terms of efficacy, need for repeat dosing with palonosetron, either daily or less frequently, in the setting of multi-day chemotherapy is not yet known. Aprepitant may be used for multi-day chemotherapy regimens likely to be highly emetogenic and associated with significant risk for delayed 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.75 Repeated dosing of aprepitant over multiple cycles is tolerated.75 Based on phase II data, aprepitant 80 mg may be safely administered on days 4 and 5 after chemotherapy.76 It is not yet known if dosing aprepitant after day 3 improves control of nausea or emesis in this clinical setting. Note that fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant (125 mg) on day 1 only. Version 1.2011,11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-11
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References
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17. Dodds LJ. The control of cancer chemotherapy-induced nausea 25. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of and vomiting. J Clin Hosp Pharm 1985;10:143-166. Available at: Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006;24:2932-2947. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16717289. 18. Kris MG, Gralla RJ, Clark RA, et al. Incidence, course, and severity of delayed nausea and vomiting following the administration of high- 26. Laszlo J. Treatment of nausea and vomiting caused by cancer dose cisplatin. J Clin Oncol 1985;3:1379-1384. Available at: chemotherapy. Cancer Treat Rev 1982;9 Suppl B:3-9. Available at: 19. Roila F, Boschetti E, Tonato M, et al. Predictive factors of delayed 27. Strum SB, McDermed JE, Pileggi J, et al. Intravenous emesis in cisplatin-treated patients and antiemetic activity and metoclopramide: prevention of chemotherapy-induced nausea and tolerability of metoclopramide or dexamethasone. A randomized single- vomiting. A preliminary evaluation. Cancer 1984;53:1432-1439. blind study. Am J Clin Oncol 1991;14:238-242. Available at: Available at: http://www.ncbi.nlm.nih.gov/pubmed/6692333. 28. Lindley CM, Bernard S, Fields SM. Incidence and duration of 20. Moher D, Arthur AZ, Pater JL. Anticipatory nausea and/or vomiting. chemotherapy-induced nausea and vomiting in the outpatient oncology Cancer Treat Rev 1984;11:257-264. Available at: population. J Clin Oncol 1989;7:1142-1149. Available at: 21. Jacobsen PB, Redd WH. The development and management of 29. Aapro M. Methodological issues in antiemetic studies. Invest New chemotherapy-related anticipatory nausea and vomiting. Cancer Invest Drugs 1993;11:243-253. Available at: 1988;6:329-336. Available at: 30. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying 22. Morrow GR. Clinical characteristics associated with the the acute emetogenicity of cancer chemotherapy. J Clin Oncol development of anticipatory nausea and vomiting in cancer patients 1997;15:103-109. Available at: undergoing chemotherapy treatment. J Clin Oncol 1984;2:1170-1176. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6491699. 31. Grunberg SM, Osoba D, Hesketh PJ, et al. Evaluation of new 23. Harding R, Young R, Anno G. Radiotherapy-induced emesis. In: antiemetic agents and definition of antineoplastic agent emetogenicity-- Andrews P, Sanger G, eds. Emesis in Anti-Cancer Therapy. London: an update. Support Care Cancer 2005;13:80-84. Available at: Chapman & Hall Medical; 1993:163-178. 24. Roila F, Hesketh PJ, Herrstedt J. Prevention of chemotherapy- and 32. Koeller JM, Aapro MS, Gralla RJ, et al. Antiemetic guidelines: radiotherapy-induced emesis: results of the 2004 Perugia International creating a more practical treatment approach. Support Care Cancer Antiemetic Consensus Conference. Ann Oncol 2006;17:20-28. 2002;10:519-522. Available at: Available at: http://www.ncbi.nlm.nih.gov/pubmed/16314401. Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-2
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33. Hesketh PJ, Gandara DR. Serotonin antagonists: a new class of 40. Marty M. A comparative study of the use of granisetron, a selective antiemetic agents. J Natl Cancer Inst 1991;83:613-620. Available at: 5-HT3 antagonist, versus a standard anti-emetic regimen of chlorpromazine plus dexamethasone in the treatment of cytostatic-induced emesis. The Granisetron Study Group. Eur J Cancer 1990;26 34. Andrews PL, Bhandari P, Davey PT, et al. Are all 5-HT3 receptor Suppl 1:S28-32. Available at: antagonists the same? Eur J Cancer 1992;28A Suppl 1:2-6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1320915. 41. Marty M, Pouillart P, Scholl S, et al. Comparison of the 5- 35. Grunberg SM, Koeller JM. Palonosetron: a unique 5-HT3-receptor hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) antagonist for the prevention of chemotherapy-induced emesis. Expert with high-dose metoclopramide in the control of cisplatin-induced Opin Pharmacother 2003;4:2297-2303. Available at: emesis. N Engl J Med 1990;322:816-821. Available at: 36. Grunberg SM, Stevenson LL, Russell CA, McDermed JE. Dose 42. Soukop M. A comparison of two dose levels of granisetron in ranging phase I study of the serotonin antagonist GR38032F for patients receiving high-dose cisplatin. The Granisetron Study Group. prevention of cisplatin-induced nausea and vomiting. J Clin Oncol Eur J Cancer 1990;26 Suppl 1:S15-19. Available at: 1989;7:1137-1141. Available at: 43. Roila F, Tonato M, Cognetti F, et al. Prevention of cisplatin-induced 37. Chevallier B. Efficacy and safety of granisetron compared with high- emesis: a double-blind multicenter randomized crossover study dose metoclopramide plus dexamethasone in patients receiving high- comparing ondansetron and ondansetron plus dexamethasone. J Clin dose cisplatin in a single-blind study. The Granisetron Study Group. Eur Oncol 1991;9:675-678. Available at: J Cancer 1990;26 Suppl 1:S33-36. Available at: 44. Fraschini G. Antiemetic activity of ondansetron in cancer patients 38. Cupissol DR, Serrou B, Caubel M. The efficacy of granisetron as a receiving non-cisplatin chemotherapy. Semin Oncol 1992;19:41-47. prophylactic anti-emetic and intervention agent in high-dose cisplatin- Available at: http://www.ncbi.nlm.nih.gov/pubmed/1387249. induced emesis. Eur J Cancer 1990;26 Suppl 1:23-27. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2169782. 45. Kamanabrou D. Intravenous granisetron--establishing the optimal dose. The Granisetron Study Group. Eur J Cancer 1992;28A Suppl 1:6- 39. De Mulder PH, Seynaeve C, Vermorken JB, et al. Ondansetron 11. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1320919. compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, 46. Sledge GW, Einhorn L, Nagy C, House K. Phase III double-blind randomized, double-blind, crossover study. Ann Intern Med comparison of intravenous ondansetron and metoclopramide as 1990;113:834-840. Available at: antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy. Cancer 1992;70:2524-2528. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1423181. Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-3
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47. Chevallier B. The control of acute cisplatin-induced emesis--a induced nausea and vomiting. J Oncol Pharm Pract 2009;15:223-231. comparative study of granisetron and a combination regimen of high- Available at: http://www.ncbi.nlm.nih.gov/pubmed/19304880. dose metoclopramide and dexamethasone. Granisetron Study Group. Br J Cancer 1993;68:176-180. Available at: 54. Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double- 48. Navari RM, Kaplan HG, Gralla RJ, et al. Efficacy and safety of blind randomized phase III trial comparing single doses of palonosetron granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in with ondansetron. Ann Oncol 2003;14:1570-1577. Available at: the prevention of nausea and vomiting induced by high-dose cisplatin. J Clin Oncol 1994;12:2204-2210. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7931490. 55. Bonneterre J, Hecquet B. Granisetron (IV) compared with ondansetron (IV plus oral) in the prevention of nausea and vomiting 49. Riviere A. Dose finding study of granisetron in patients receiving induced by moderately-emetogenic chemotherapy. A cross-over study. high-dose cisplatin chemotherapy. The Granisetron Study Group. Br J Bull Cancer 1995;82:1038-1043. Available at: Cancer 1994;69:967-971. Available at: 56. Jantunen IT, Kataja VV, Johansson RT. Ondansetron and 50. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved tropisetron with dexamethasone in the prophylaxis of acute vomiting prevention of moderately emetogenic chemotherapy-induced nausea induced by non-cisplatin-containing chemotherapy. Acta Oncol and vomiting with palonosetron, a pharmacologically novel 5-HT3 1992;31:573-575. Available at: receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 2003;98:2473-2482. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14635083. 57. Jantunen IT, Muhonen TT, Kataja VV, et al. 5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately 51. Aapro MS. Palonosetron as an anti-emetic and anti-nausea agent in emetogenic chemotherapy--a randomised study. Eur J Cancer oncology. Ther Clin Risk Manag 2007;3:1009-1020. Available at: 1993;29A:1669-1672. Available at: 52. Grunberg S, Gabrial N, Clark G. Phase III trial of transdermal 58. Martoni A, Angelelli B, Guaraldi M, et al. An open randomised granisetron patch (Sancuso) compared to oral granisetron (OG) for cross-over study on granisetron versus ondansetron in the prevention chemotherapy-induced nausea and vomiting (CINV) after multi-day of acute emesis induced by moderate dose cisplatin-containing moderately emetogenic (MEC) or highly emetogenic (HEC) regimens. Eur J Cancer 1996;32A:82-85. Available at: chemotherapy [abstract P-18] [abstract]. Presented at the MASCC/ISOO 20th Anniversary International Symposium Supportive Care in Cancer; St. Gallen, Switzerland. 687. 59. Campora E, Simoni C, Rosso R. [Tropisetron versus ondansetron in the prevention and control of emesis in patients undergoing 53. Howell J, Smeets J, Drenth HJ, Gill D. Pharmacokinetics of a chemotherapy with FAC/FEC for metastatic or surgically treated breast granisetron transdermal system for the treatment of chemotherapy- Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-4
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Antiemesis
carcinoma]. Minerva Med 1994;85:25-31. Available at: 66. Navari R, Gandara D, Hesketh P, et al. Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol 1995;13:1242- 60. Gebbia V, Cannata G, Testa A, et al. Ondansetron versus 1248. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7738628. granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial. Cancer 67. Stewart A, McQuade B, Cronje JD, et al. Ondansetron compared 1994;74:1945-1952. Available at: with granisetron in the prophylaxis of cyclophosphamide-induced emesis in out-patients: a multicentre, double-blind, double-dummy, randomised, parallel-group study. Emesis Study Group for 61. Mantovani G, Maccio A, Bianchi A, et al. Comparison of Ondansetron and Granisetron in Breast Cancer Patients. Oncology granisetron, ondansetron, and tropisetron in the prophylaxis of acute 1995;52:202-210. Available at: nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial. Cancer 1996;77:941-948. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8608488. 68. Audhuy B, Cappelaere P, Martin M, et al. A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous 62. Noble A, Bremer K, Goedhals L, et al. A double-blind, randomised, doses of dolasetron mesilate and granisetron in patients receiving high crossover comparison of granisetron and ondansetron in 5-day dose cisplatin chemotherapy. Eur J Cancer 1996;32A:807-813. fractionated chemotherapy: assessment of efficacy, safety and patient Available at: http://www.ncbi.nlm.nih.gov/pubmed/9081358. preference. The Granisetron Study Group. Eur J Cancer 1994;30A:1083-1088. Available at: 69. Fauser AA, Duclos B, Chemaissani A, et al. Therapeutic equivalence of single oral doses of dolasetron mesilate and multiple doses of ondansetron for the prevention of emesis after moderately 63. Ruff P, Paska W, Goedhals L, et al. Ondansetron compared with emetogenic chemotherapy. European Dolasetron Comparative Study granisetron in the prophylaxis of cisplatin-induced acute emesis: a Group. Eur J Cancer 1996;32A:1523-1529. Available at: multicentre double-blind, randomised, parallel-group study. The Ondansetron and Granisetron Emesis Study Group. Oncology 1994;51:113-118. Available at: 70. Hesketh P, Navari R, Grote T, et al. Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute 64. Ondansetron versus granisetron, both combined with cisplatin-induced emesis in patients with cancer. Dolasetron dexamethasone, in the prevention of cisplatin-induced emesis. Italian Comparative Chemotherapy-induced Emesis Prevention Group. J Clin Group of Antiemetic Research. Ann Oncol 1995;6:805-810. Available Oncol 1996;14:2242-2249. Available at: at: http://www.ncbi.nlm.nih.gov/pubmed/8589019. 65. Marty M, Kleisbauer JP, Fournel P, et al. Is Navoban (tropisetron) 71. Lofters WS, Pater JL, Zee B, et al. Phase III double-blind as effective as Zofran (ondansetron) in cisplatin-induced emesis? The comparison of dolasetron mesylate and ondansetron and an evaluation French Navoban Study Group. Anticancer Drugs 1995;6 Suppl 1:15-21. of the additive role of dexamethasone in the prevention of acute and Available at: http://www.ncbi.nlm.nih.gov/pubmed/7749165. delayed nausea and vomiting due to moderately emetogenic Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-5
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Antiemesis
chemotherapy. J Clin Oncol 1997;15:2966-2973. Available at: 72. Jordan K, Hinke A, Grothey A, et al. A meta-analysis comparing the 78. Warr DG, Hesketh PJ, Gralla RJ, et al. Efficacy and tolerability of efficacy of four 5-HT3-receptor antagonists for acute chemotherapy- aprepitant for the prevention of chemotherapy-induced nausea and induced emesis. Support Care Cancer 2007;15:1023-1033. Available vomiting in patients with breast cancer after moderately emetogenic at: http://www.ncbi.nlm.nih.gov/pubmed/17205281. chemotherapy. J Clin Oncol 2005;23:2822-2830. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15837996. 73. Huang JQ, Zheng GF, Deuson R, et al. Do 5-hydroxytryptamine3 receptor antagonists (5-HT3) improve the antiemetic effect of 79. Gralla RJ, Warr DG, Carides AD, et al. Effect of aprepitant on dexamethasone for preventing delayed chemotherapy-induced nausea antiemetic protection in patients receiving moderately emetogenic and vomiting (CINV)? A meta-analysis of randomized controlled trials chemotherapy plus high-dose cisplatin: Analysis of combined data from [abstract]. J Clin Oncol 2004;22 (Suppl 14): Abstract 6037. Available at: 2 phase III randomized clinical trials [abstract]. J Clin Oncol 2004;22 (Suppl 14):Abstract 8137. Available at: http://meeting.ascopubs.org/cgi/content/abstract/22/14_suppl/8137. 74. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced 80. Tremont-Lukats IW, Gonzalez-Barboteo J, Bruera E, Brescia FJ. nausea and vomiting: a multinational, randomized, double-blind, Meta-analysis of neurokinin-1 receptor antagonists (NK-1 RA) for placebo-controlled trial in patients receiving high-dose cisplatin--the chemotherapy-induced nausea and vomiting (CINV) [abstract]. J Clin Aprepitant Protocol 052 Study Group. J Clin Oncol 2003;21:4112-4119. Oncol 2004;22 (Suppl 14):Abstract 8047. Available at: Available at: http://www.ncbi.nlm.nih.gov/pubmed/14559886. 75. de Wit R, Herrstedt J, Rapoport B, et al. The oral NK(1) antagonist, 81. Grote T, Hajdenberg J, Cartmell A, et al. Combination therapy for aprepitant, given with standard antiemetics provides protection against chemotherapy-induced nausea and vomiting in patients receiving nausea and vomiting over multiple cycles of cisplatin-based moderately emetogenic chemotherapy: palonosetron, dexamethasone, chemotherapy: a combined analysis of two randomised, placebo- and aprepitant. J Support Oncol 2006;4:403-408. Available at: controlled phase III clinical trials. Eur J Cancer 2004;40:403-410. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14746859. 82. Grunberg SM, Dugan M, Muss H, et al. Effectiveness of a single- 76. Chawla SP, Grunberg SM, Gralla RJ, et al. Establishing the dose of day three-drug regimen of dexamethasone, palonosetron, and the oral NK1 antagonist aprepitant for the prevention of chemotherapy- aprepitant for the prevention of acute and delayed nausea and vomiting induced nausea and vomiting. Cancer 2003;97:2290-2300. Available at: caused by moderately emetogenic chemotherapy. Support Care Cancer 2009;17:589-594. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19037667. 77. Warr DG, Eisenberg P, Hesketh PJ, et al. Effect of aprepitant for the prevention of nausea and vomiting after one cycle of moderately 83. Shadle CR, Lee Y, Majumdar AK, et al. Evaluation of potential emetogenic chemotherapy: A randomized double-blind trial in 866 inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 patients [abstract]. J Clin Oncol 2004;22 (Suppl 14):Abstract 8007. Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-6
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Antiemesis
activity. J Clin Pharmacol 2004;44:215-223. Available at: 91. Cassileth PA, Lusk EJ, Torri S, et al. Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. Arch Intern Med 1983;143:1347-1349. Available at: 84. Wampler G. The pharmacology and clinical effectiveness of phenothiazines and related drugs for managing chemotherapy-induced emesis. Drugs 1983;25 Suppl 1:35-51. Available at: 92. Kris MG, Gralla RJ, Clark RA, et al. Consecutive dose-finding trials adding lorazepam to the combination of metoclopramide plus dexamethasone: improved subjective effectiveness over the 85. Gralla RJ, Itri LM, Pisko SE, et al. Antiemetic efficacy of high-dose combination of diphenhydramine plus metoclopramide plus metoclopramide: randomized trials with placebo and prochlorperazine dexamethasone. Cancer Treat Rep 1985;69:1257-1262. Available at: in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 1981;305:905-909. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7024807. 93. Kris MG, Gralla RJ, Clark RA, et al. Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or 86. Gralla RJ, Tyson LB, Bordin LA, et al. Antiemetic therapy: a review diphenhydramine when used in combination with metoclopramide plus of recent studies and a report of a random assignment trial comparing dexamethasone. A double-blind, randomized trial. Cancer metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treat Rep 1987;60:2816-2822. Available at: 1984;68:163-172. Available at: 94. Herman TS, Einhorn LH, Jones SE, et al. Superiority of nabilone 87. Bakowski MT. Advances in anti-emetic therapy. Cancer Treat Rev over prochlorperazine as an antiemetic in patients receiving cancer 1984;11:237-256. Available at: chemotherapy. N Engl J Med 1979;300:1295-1297. Available at: 88. Grossman B, Lessin LS, Cohen P. Droperidol prevents nausea and 95. Steele N, Gralla RJ, Braun DW, Young CW. Double-blind vomiting from cis-platinum. N Engl J Med 1979;301:47. Available at: comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treat Rep 1980;64:219-224. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6250699. 89. Aapro MS, Alberts DS. High-dose dexamethasone for prevention of cis-platin-induced vomiting. Cancer Chemother Pharmacol 1981;7:11- 96. Navari RM, Einhorn LH, Loehrer PJ, et al. A phase II trial of 14. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6122510. olanzapine for the prevention of chemotherapy induced nausea and vomiting (CINV) [abstract]. J Clin Oncol 2004;22 (Suppl 14):Abstract 90. Aapro MS, Plezia PM, Alberts DS, et al. Double-blind crossover 8046. Available at: study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide. J Clin Oncol 1984;2:466-471. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6539363. 97. Navari RM, Einhorn LH, Passik SD, et al. A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier Oncology Group study. Support Care Cancer Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-7
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NCCN Guidelines™ Version 1.2011
Antiemesis
2005;13:529-534. Available at: 105. Roila F, Warr D, Clark-Snow RA, et al. Delayed emesis: moderately emetogenic chemotherapy. Support Care Cancer 2005;13:104-108. Available at: 98. Srivastava M, Brito-Dellan N, Davis MP, et al. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom Manage 2003;25:578-582. Available at: 106. Massa E, Astara G, Madeddu C, et al. Palonosetron plus dexamethasone effectively prevents acute and delayed chemotherapy-induced nausea and vomiting following highly or moderately 99. Passik SD, Navari RM, Jung S-H, et al. A phase I trial of olanzapine emetogenic chemotherapy in pre-treated patients who have failed to (Zyprexa) for the prevention of delayed emesis in cancer patients: a respond to a previous antiemetic treatment: comparison between Hoosier Oncology Group study. Cancer Invest 2004;22:383-388. elderly and non-elderly patient response. Crit Rev Oncol Hematol Available at: http://www.ncbi.nlm.nih.gov/pubmed/15493359. 2009;70:83-91. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18723369. 100. Passik SD, Kirsh KL, Theobald DE, et al. A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in 107. Grunberg S, Clark-Snow RA, Koeller J. Chemotherapy-induced cancer patients. J Pain Symptom Manage 2003;25:485-488. Available nausea and vomiting: contemporary approaches to optimal at: http://www.ncbi.nlm.nih.gov/pubmed/12727048. management : Proceedings from a symposium at the 2008 Multinational Association of Supportive Care in Cancer (MASCC) 101. Passik SD, Lundberg J, Kirsh KL, et al. A pilot exploration of the Annual Meeting. Support Care Cancer 2010. Available at: antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage 2002;23:526-532. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12067777. 108. Ormrod D, Goa KL. Intranasal metoclopramide. Drugs 1999;58:315-322; discussion 323-314. Available at: 102. Morita T, Tei Y, Shishido H, Inoue S. Olanzapine-induced delirium in a terminally ill cancer patient. J Pain Symptom Manage 2004;28:102-103. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15276190. 109. Maranzano E, Feyer P, Molassiotis A, et al. Evidence-based recommendations for the use of antiemetics in radiotherapy. Radiother 103. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone Oncol 2005;76:227-233. Available at: versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009;10:115- 110. Franzen L, Nyman J, Hagberg H, et al. A randomised placebo 124. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19135415. controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 1996;7:587-592. Available at: 104. Geling O, Eichler H-G. Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence 111. Wong RK, Paul N, Ding K, et al. 5-hydroxytryptamine-3 receptor and drug cost implications. J Clin Oncol 2005;23:1289-1294. Available antagonist with or without short-course dexamethasone in the at: http://www.ncbi.nlm.nih.gov/pubmed/15718327. prophylaxis of radiation induced emesis: a placebo-controlled Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-8
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Antiemesis
randomized trial of the National Cancer Institute of Canada Clinical Altern Complement Med 2006;12:489-495. Available at: Trials Group (SC19). J Clin Oncol 2006;24:3458-3464. Available at: 119. Figueroa-Moseley C, Jean-Pierre P, Roscoe JA, et al. Behavioral 112. Belkacemi Y, Ozsahin M, Pene F, et al. Total body irradiation prior interventions in treating anticipatory nausea and vomiting. J Natl Compr to bone marrow transplantation: efficacy and safety of granisetron in the Canc Netw 2007;5:44-50. Available at: prophylaxis and control of radiation-induced emesis. Int J Radiat Oncol Biol Phys 1996;36:77-82. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8823261. 120. Molassiotis A, Yung HP, Yam BM, et al. The effectiveness of progressive muscle relaxation training in managing chemotherapy- 113. Okamoto S, Takahashi S, Tanosaki R, et al. Granisetron in the induced nausea and vomiting in Chinese breast cancer patients: a prevention of vomiting induced by conditioning for stem cell randomised controlled trial. Support Care Cancer 2002;10:237-246. transplantation: a prospective randomized study. Bone Marrow Available at: http://www.ncbi.nlm.nih.gov/pubmed/11904789. Transplant 1996;17:679-683. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8733681. 121. Razavi D, Delvaux N, Farvacques C, et al. Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant 114. Aapro MS, Molassiotis A, Olver I. Anticipatory nausea and chemotherapy: a double-blind, placebo-controlled study assessing the vomiting. Support Care Cancer 2005;13:117-121. Available at: usefulness of alprazolam. J Clin Oncol 1993;11:1384-1390. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8315437. 115. Ezzo J, Vickers A, Richardson MA, et al. Acupuncture-point 122. Malik IA, Khan WA, Qazilbash M, et al. Clinical efficacy of stimulation for chemotherapy-induced nausea and vomiting. J Clin lorazepam in prophylaxis of anticipatory, acute, and delayed nausea Oncol 2005;23:7188-7198. Available at: and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol 1995;18:170-175. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7900711. 116. Morrow GR, Morrell C. Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. N Engl J Med 123. Ellebaek E, Herrstedt J. Optimizing antiemetic therapy in multiple- 1982;307:1476-1480. Available at: day and multiple cycles of chemotherapy. Curr Opin Support Palliat Care 2008;2:28-34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18685391. 117. Redd WH, Andrykowski MA. Behavioral intervention in cancer treatment: controlling aversion reactions to chemotherapy. J Consult 124. Einhorn LH, Rapoport B, Koeller J, et al. Antiemetic therapy for Clin Psychol 1982;50:1018-1029. Available at: multiple-day chemotherapy and high-dose chemotherapy with stem cell transplant: review and consensus statement. Support Care Cancer 2005;13:112-116. Available at: 118. Ezzo J, Streitberger K, Schneider A. Cochrane systematic reviews examine P6 acupuncture-point stimulation for nausea and vomiting. J Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®. REF-9
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Antiemesis
125. Navari RM. Prevention of emesis from multiple-day and high-dose germ cell cancer. Support Care Cancer 2007;15:1293-1300. Available chemotherapy regimens. J Natl Compr Canc Netw 2007;5:51-59. at: http://www.ncbi.nlm.nih.gov/pubmed/17436025. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17239326. 126. Herrstedt J, Sigsgaard TC, Nielsen HA, et al. Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy. Support Care Cancer 2007;15:417-426. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17093916. 127. Musso M, Scalone R, Bonanno V, et al. Palonosetron (Aloxi) and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving multiple-day chemotherapy. Support Care Cancer 2009;17:205-209. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18839220. 128. Celio L, Denaro A, Canova S, et al. Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting. Tumori 2008;94:447-452. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18822676. 129. Aapro MS, Grunberg SM, Manikhas GM, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 2006;17:1441-1449. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16766588. 130. Eisenberg P, MacKintosh FR, Ritch P, et al. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol 2004;15:330-337. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14760130. 131. Einhorn LH, Brames MJ, Dreicer R, et al. Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for Version 1.2011, 11/30/10 National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines™ and this illustration may not be reproduced in any form without the express written permission of NCCN®.REF-10

Source: http://enotes.us/CancerAntiEmesisRx2011.pdf

Introducing pd

EHR Integration in Point of Service Systems: Patient Care Storyboard The Patient Medication Profile The Pharmaceutical Information Network (PIN) is one component of the EHR; it is the central repository of the patient's Medication Profile. Medication and allergy information is loaded into the EHR from pharmacies,

risksummit.eu

Symposium on Risk versus Hazard Symposium on Risk versus Hazard Risk versus Hazard – How to Regulate in the 21st Century Ragnar E. Lofstedt* In Europe, debate as to whether one should regulate chemicals based on intrinsic hazard or assessment of risk, or possibly a combination of both, has been gaining momentum. This article first provides a brief history of this risk versus hazard debate. Secondly, it ex-amines how European regulators are currently handling the regulation of two chemical compounds, namely Bisphenol A and Deca BDE (a brominated flame retardant), based on forty-five expert interviews with regulators, policy makers and industry representatives in eight Member States, as well as with European Commission officials. The paper shows that there is no clear consensus as to when risk or hazard considerations should be the basis for regulatory decision-making, with wide discrepancies between Member States (e.g. the UK is overall more risk based than Sweden) and between regulatory agencies within Member States. The penultimate section puts forward a series of recommendations to help regula-tors and policy makers develop more consistent and science based regulations for Europe.