© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`572
`Overview
`Chemotherapy-induced vomiting (emesis) and nau-
`sea can significantly affect a patient’s quality of life,
`leading to poor compliance with further chemother-
`apy treatment. Nausea and vomiting can also result
`in metabolic imbalances, degeneration of self-care
`and functional ability, nutrient depletion, anorexia,
`decline of performance and mental status, wound de-
`hiscence, esophageal tears, and withdrawal from po-
`tentially useful or curative anticancer treatment.
`1–4
`The incidence and severity of nausea and/or
`vomiting in patients undergoing chemotherapy are
`affected by numerous factors, including 1) the spe -
`cific chemotherapeutic agents used, 2) dosage of the
`agents, 3) schedule and route of administration of
`the agents, and 4) individual patient variability (e.g.,
`The NCCN
`Antiemesis
`Clinical Practice Guidelines in OncologyTM
`David S. Ettinger, MD; Debra K. Armstrong, RN;
`Sally Barbour, PharmD, BCOP; Michael J. Berger, PharmD, BCOP;
`Philip J. Bierman, MD; Bob Bradbury, BCPS; Georgianna Ellis, MD;
`Steve Kirkegaard, PharmD; Dwight D. Kloth, PharmD, FCCP , BCOP;
`Mark G. Kris, MD; Dean Lim, MD;
`Michael Anne Markiewicz, PharmD; Lida Nabati, MD;
`Carli Nesheiwat, PharmD, BCOP; Hope S. Rugo, MD;
`Steven M. Sorscher, MD; Lisa Stucky-Marshal, RN, MS;
`Barbara Todaro, PharmD; and Susan Urba, MD
`Antiemesis Clinical Practice Guidelines in
`Oncology
`Key Words
`NCCN Clinical Practice Guidelines, antiemesis, nausea and
`vomiting, chemotherapy-induced, 5-HT3–receptor antago-
`nists, NK-1–receptor antagonists (JNCCN 2009;7:572–595)
`NCCN Categories of Evidence and Consensus
`Category 1: The recommendation is based on high-level
`evidence (e.g., randomized controlled trials) and there is
`uniform NCCN consensus.
`Category 2A: The recommendation is based on lower-
`level evidence and there is uniform NCCN consensus.
`Category 2B: The recommendation is based on lower-
`level evidence
`and there is nonuniform NCCN consensus
`(but no major disagreement).
`Category 3: The recommendation is based on any level of
`evidence but reflects major disagreement.
`All recommendations are category 2A unless otherwise
`noted.
`Clinical trials: The NCCN believes that the best management
`for any cancer patient is in a clinical trial. Participation in
`clinical trials is especially encouraged.
`Please Note
`These guidelines are a statement of consensus of the
`authors regarding their views of currently accepted ap -
`proaches to treatment. Any clinician seeking to apply or
`consult these guidelines is expected to use independent
`medical judgment in the context of individual clinical cir-
`cumstances to determine any patient’s care or treatment.
`The National Comprehensive Cancer Network makes no
`representation or warranties of any kind regarding their
`content, use, or application and disclaims any responsibil-
`ity for their applications or use in any way.
`These guidelines are copyrighted by the National
`Comprehensive Cancer Network. All rights reserved.
`These guidelines and the illustrations herein may not be
`reproduced in any form without the express written per -
`mission of the NCCN © 2009.
`Disclosures for the NCCN Antiemesis
`Guidelines Panel
`At the beginning of each NCCN guidelines panel meeting,
`panel members disclosed any financial support they have
`received from industry. Through 2008, this information was
`published in an aggregate statement in JNCCN and on-line.
`Furthering NCCN’s commitment to public transparency, this
`disclosure process has now been expanded by listing all
`potential conflicts of interest respective to each individual
`expert panel member.
`Individual disclosures for the NCCN Antiemesis Guidelines
`Panel members can be found on page 595. (To view the most
`recent version of these guidelines and accompanying disclo-
`sures, visit the NCCN Web site at www.nccn.org.)
`These guidelines are also available on the Internet. For the
`latest update, please visit www.nccn.org.
`HELSINN EXHIBIT 2037
`Azurity Pharmaceuticals, Inc. v. Helsinn Healthcare S.A.
`IPR2025-00945
`Page 1 of 24
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`Antiemesis
`NCCN
`Clinical Practice Guidelines
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`573
`Journal of the National Comprehensive Cancer Network
`Text continues on p. 585
`age, sex, prior chemotherapy, history of alcohol use).
`Approximately 70% to 80% of all patients undergo -
`ing chemotherapy experience nausea and/or vomit -
`ing,5,6 whereas 10% to 44% experience anticipatory
`nausea and/or vomiting; 7–10 patients often experi -
`ence more nausea than vomiting.11
`Pathophysiology of Emesis
`Vomiting results from stimulation of a multistep re -
`flex pathway controlled by the brain, and is triggered
`by afferent impulses to the vomiting center (located
`in the medulla) from the chemoreceptor trigger zone;
`pharynx and gastrointestinal tract (by way of vagal
`afferent 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.
`12
`The chemoreceptor trigger zone, vomiting
`center, and gastrointestinal tract have many neu-
`rotransmitter receptors. Activation of these recep -
`tors by chemotherapeutic agents or their metabo -
`lites may be responsible for chemotherapy-induced
`emesis. Principal neuroreceptors involved in the
`emetic response are serotonin (5-hydroxytryptamine
`[5-HT3]) and dopamine receptors;
`13,14 other neu-
`roreceptors include acetylcholine, corticosteroid,
`histamine, cannabinoid, opiate, and neurokinin-1
`(NK-1) receptors, which are located in the vomiting
`and vestibular centers of the brain.
`15
`Antiemetic agents can block different neuronal
`pathways, exert their effects at different points dur -
`NCCN Antiemesis Panel Members
`*David S. Ettinger, MD/Chair†
`The Sidney Kimmel Comprehensive Cancer Center at
`Johns Hopkins
`Debra K. Armstrong, RN#
`Vanderbilt-Ingram Cancer Center
`Sally Barbour, PharmD, BCOP
`∑
`Duke Comprehensive Cancer Center
`Michael J. Berger, PharmD, BCOP∑
`The Ohio State University Comprehensive Cancer Center –
`James Cancer Hospital and Solove Research Institute
`Philip J. Bierman, MD†‡
`UNMC Eppley Cancer Center at
`The Nebraska Medical Center
`Bob Bradbury, BCPS∑
`H.
`Lee Moffitt Cancer Center & Research Institute
`Georgianna Ellis, MD†
`Fred Hutchinson Cancer Research Center/
`Seattle Cancer Care Alliance
`Steve Kirkegaard, PharmD∑
`Huntsman Cancer Institute at the University of Utah
`*Dwight D. Kloth, PharmD, FCCP, BCOP∑
`Fox Chase Cancer Center
`*Mark G. Kris, MD†
`Memorial Sloan-Kettering Cancer Center
`Dean Lim, MD†
`City of Hope Comprehensive Cancer Center
`Michael Anne Markiewicz, PharmD∑
`University of Alabama at Birmingham
`Comprehensive Cancer Center
`Lida Nabati, MD£Þ
`Dana-Farber/Brigham and Women’s Cancer Center
`Carli Nesheiwat, PharmD, BCOP∑
`St. Jude Children’s Research Hospital/
`University of Tennessee Cancer Institute
`Hope S. Rugo, MD†‡
`UCSF Helen Diller Family Comprehensive Cancer Center
`Steven M. Sorscher, MD†
`Siteman Cancer Center at Barnes-Jewish Hospital and
`Washington University School of Medicine
`Lisa Stucky-Marshal, RN, MS#
`Robert H. Lurie Comprehensive Cancer Center of
`Northwestern University
`Barbara Todaro, PharmD∑
`Roswell Park Cancer Institute
`Susan Urba, MD†£
`University of Michigan Comprehensive Cancer Center
`KEY:
`*Writing Committee Member
`Specialties: †Medical Oncology; #Nurse; ∑Pharmacology; ‡He-
`matology/Hematology Oncology; £Supportive Care, Including
`Palliative, Pain Management, Pastoral Care, and Oncology
`Social Work; ÞInternal Medicine
`Page 2 of 24
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`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`574
`Antiemesis Version 3:2009
`Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`All recommendations are category 2A unless otherwise noted.
`PRINCIPLES OF EMESIS CONTROL IN THE CANCER PATIENT
`Preventing nausea/vomiting is the goal.
`The risk for nausea/vomiting in persons undergoing chemotherapy of high and moderate emetic risk lasts at
`least 4 days for high and 3 days for moderate. Patients must be protected throughout the full period of risk.
`Oral and IV antiemetic formulations have equivalent efficacy.
`Consider the toxicity of the specific antiemetic(s).
`Choice of antiemetic(s) used should be based on the emetic risk of the therapy, prior experience with
`antiemetics, and patient-specific factors.
`Other potential causes of emesis in cancer patients 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- (e.g., vincristine) induced
`Psychophysiologic:
`For use of antiemetics for nausea and vomiting that are not related to radiation and/or chemotherapy, see
`NCCN Clinical Practice Guidelines in Oncology: Palliative Care.*
`For multidrug regimens, select antiemetic therapy based on drug with the highest emetic risk. See Emetogenic
`Potential of Antineoplastic Agents (page 580).
`Consider using an blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea.
`Anxiety
`Anticipatory nausea and vomiting
`H2
`HIGH EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONb,c
`Higha
`Start before chemotherapy
`Aprepitant 125 mg PO day 1 or fosaprepitant 115 mg day 1,d
`80 mg PO daily days 2-3
`and
`Dexamethasone 12 mg PO or IV days 1-4
`and
`Palonosetron 0.25 mg IV day 1 (preferred, category 2B)e
`or
`Dolasetron 100 mg PO or 1.8 mg/kg IV or 100 mg IV day 1f
`or
`f
`Ondansetron 16-24 mg PO or 8-12 mg (maximum 32 mg) IV day 1f
`± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 or every 6 h prn days 1-4
`± H blocker or proton pump inhibitor
`b,c
`5-HT3 antagonist:
`Granisetron 2 mg PO or 1 mg PO bid or 0.01 mg/kg (maximum 1 mg) IV day 1 or transdermal
`patch containing 34.3 mg granisetron applied 24-48 h before first dose of chemotherapy
`or
`and
`2
`See
`Breakthrough
`Treatment
`(pages 578 and 579)
`(category 1, for
`combined regimen)
`a 2
`b
`c
`d
`e
`f
`Data for post-cisplatin ( 50 mg/m ) emesis prevention are category 1, others are category 2A.
`Antiemetic regimens should be chosen based on the drug with the highest emetic risk and on patient-specific risk factors.
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant (125 mg) 30 minutes before chemotherapy, on day 1 only of the chemotherapy-
`induced nausea and vomiting regimen as an infusion administered over 15 minutes.
`In a randomized study, a larger dose of palonosetron was used without aprepitant. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone
`versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised,
`comparative phase III trial. Lancet Oncol 2009;10:115-124.
`Order of listed antiemetics does not reflect preference.
`*To view the most recent version of these guidelines, visit the NCCN Web site at www.nccn.org.
`See Principles of Emesis Control (opposite page)
`Page 3 of 24
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`NCCN Clinical Practice Guidelines in Oncology
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`575
`Antiemesis Version 3:2009
`Version 3.2009, 04-01-09 ©2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be
`reproduced in any form without the express written permission of NCCN.
`PRINCIPLES OF EMESIS CONTROL IN THE CANCER PATIENT
`Preventing nausea/vomiting is the goal.
`The risk for nausea/vomiting in persons undergoing chemotherapy of high and moderate emetic risk lasts at
`least 4 days for high and 3 days for moderate. Patients must be protected throughout the full period of risk.
`Oral and IV antiemetic formulations have equivalent efficacy.
`Consider the toxicity of the specific antiemetic(s).
`Choice of antiemetic(s) used should be based on the emetic risk of the therapy, prior experience with
`antiemetics, and patient-specific factors.
`Other potential causes of emesis in cancer patients 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- (e.g., vincristine) induced
`Psychophysiologic:
`For use of antiemetics for nausea and vomiting that are not related to radiation and/or chemotherapy, see
`NCCN Clinical Practice Guidelines in Oncology: Palliative Care.*
`For multidrug regimens, select antiemetic therapy based on drug with the highest emetic risk. See Emetogenic
`Potential of Antineoplastic Agents (page 580).
`Consider using an blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea.
`Anxiety
`Anticipatory nausea and vomiting
`H2
`HIGH EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONb,c
`Higha
`Start before chemotherapy
`Aprepitant 125 mg PO day 1 or fosaprepitant 115 mg day 1,d
`80 mg PO daily days 2-3
`and
`Dexamethasone 12 mg PO or IV days 1-4
`and
`Palonosetron 0.25 mg IV day 1 (preferred, category 2B)e
`or
`Dolasetron 100 mg PO or 1.8 mg/kg IV or 100 mg IV day 1f
`or
`f
`Ondansetron 16-24 mg PO or 8-12 mg (maximum 32 mg) IV day 1f
`± Lorazepam 0.5-2 mg PO or IV or sublingual either every 4 or every 6 h prn days 1-4
`± H blocker or proton pump inhibitor
`b,c
`5-HT3 antagonist:
`Granisetron 2 mg PO or 1 mg PO bid or 0.01 mg/kg (maximum 1 mg) IV day 1 or transdermal
`patch containing 34.3 mg granisetron applied 24-48 h before first dose of chemotherapy
`or
`and
`2
`See
`Breakthrough
`Treatment
`(pages 578 and 579)
`(category 1, for
`combined regimen)
`a 2
`b
`c
`d
`e
`f
`Data for post-cisplatin ( 50 mg/m ) emesis prevention are category 1, others are category 2A.
`Antiemetic regimens should be chosen based on the drug with the highest emetic risk and on patient-specific risk factors.
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant (125 mg) 30 minutes before chemotherapy, on day 1 only of the chemotherapy-
`induced nausea and vomiting regimen as an infusion administered over 15 minutes.
`In a randomized study, a larger dose of palonosetron was used without aprepitant. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone
`versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised,
`comparative phase III trial. Lancet Oncol 2009;10:115-124.
`Order of listed antiemetics does not reflect preference.
`*To view the most recent version of these guidelines, visit the NCCN Web site at www.nccn.org.
`See Principles of Emesis Control (opposite page)
`Page 4 of 24
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`
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`576
`Antiemesis Version 3:2009
`Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`All recommendations are category 2A unless otherwise noted.
`MODERATE EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONb,c
`Day 1 Days 2-3
`Moderatee
`Aprepitant 80 mg PO days 2-3 if used on day 1
`± Dexamethasone 12 mg PO or IV daily
`or
`Dexamethasone 12 mg PO or IV daily
`or
`5-HT3 antagonist:
`Dolasetron 100 mg PO daily or 1.8 mg/kg IV
`or
`Granisetron 1-2 mg PO daily or 1 mg PO bid or
`0.01 mg/kg (maximum 1 mg) IV
`or
`Ondansetron 8 mg PO bid or 16 mg PO daily
`or 8 mg (maximum 32 mg/d) IV
`± Lorazepam 0.5-2 mg PO or IV or sublingual
`either every 4 or 6 h prn
`± H blocker or proton pump inhibitor
`f,h
`2
`Start before chemotherapy
`Aprepitant 125 mg PO or fosaprepitant
`115 mg IV day 1 in select patients
`and
`Dexamethasone 12 mg PO or IV
`and
`5-HT3 antagonist:
`Dolasetron 100 mg PO or 1.8 mg/kg or
`100 mg IV (category 1)
`or
`Granisetron 1-2 mg PO or 1 mg PO bid
`(category 1) or 0.01 mg/kg (maximum 1
`mg) IV or transdermal patch containing
`34.3 mg granisetron applied 24-48 h
`before first dose of chemotherapy
`or
`Ondansetron 16-24 mg PO or 8-12 mg
`(maximum 32 mg/d) IV (category 1)
`or
`Palonosetron 0.25 mg IV (category 1)
`and
`± Lorazepam 0.5-2 mg PO or IV or
`sublingual either every 4 or every 6 h prn
`± H blocker or proton pump inhibitor
`b,c
`d g
`f
`2
`See
`Breakthrough
`Treatment
`(pages 578 and 579)
`Low
`Minimal Nausea/emesis (0–24 h)
`Consider using antiemetics listed under
`primary prophylaxis as treatment for low
`emetogenic-potential drugs
`LOW AND MINIMAL EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONb,c
`No routine
`prophylaxis
`See
`Breakthrough
`Treatment
`(pages 578 and 579)
`b
`c
`d
`f
`g
`h 2 2 2
`Antiemetic regimens should be chosen based on the drug with the highest emetic risk and on patient-specific risk factors.
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant (125 mg) 30 minutes before chemotherapy, on day 1 only of the chemotherapy-
`induced nausea and vomiting regimen as an infusion administered over 15 minutes.
`Order of listed antiemetics does not reflect preference.
`Aprepitant should be added (to dexamethasone and a 5-HT3 antagonist regimen) for select patients undergoing other chemotherapies of moderate emetic
`risk (e.g., carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan, methotrexate).
`Data for post-carboplatin ( 300 mg/m , cyclophosphamide 600-1000 mg/m , doxorubicin 50 mg/m ) emesis prevention are category 1.
`Start before chemotherapy
`Dexamethasone 12 mg PO or IV daily
`or
`b,c
`Repeat daily for fractionated doses of chemotherapy
`Metoclopramide 10-40 mg PO or IV either every 4 or every 6 h
`or
`Prochlorperazine 10 mg PO or IV every 4 or every 6 h
`± Lorazepam, 0.5-2 mg PO or IV either every 4 or every 6 h prn
`± H blocker or proton pump inhibitor
`i
`i
`2
`b
`c
`i
`Antiemetic regimens should be chosen based on the drug with the highest emetic risk and on patient-specific risk factors.
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Monitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or every 6 h for dystonic reactions.
`Page 5 of 24
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`
`NCCN Clinical Practice Guidelines in Oncology
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`577
`Antiemesis Version 3:2009
`Version 3.2009, 04-01-09 ©2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be
`reproduced in any form without the express written permission of NCCN.
`MODERATE EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONb,c
`Day 1 Days 2-3
`Moderatee
`Aprepitant 80 mg PO days 2-3 if used on day 1
`± Dexamethasone 12 mg PO or IV daily
`or
`Dexamethasone 12 mg PO or IV daily
`or
`5-HT3 antagonist:
`Dolasetron 100 mg PO daily or 1.8 mg/kg IV
`or
`Granisetron 1-2 mg PO daily or 1 mg PO bid or
`0.01 mg/kg (maximum 1 mg) IV
`or
`Ondansetron 8 mg PO bid or 16 mg PO daily
`or 8 mg (maximum 32 mg/d) IV
`± Lorazepam 0.5-2 mg PO or IV or sublingual
`either every 4 or 6 h prn
`± H blocker or proton pump inhibitor
`f,h
`2
`Start before chemotherapy
`Aprepitant 125 mg PO or fosaprepitant
`115 mg IV day 1 in select patients
`and
`Dexamethasone 12 mg PO or IV
`and
`5-HT3 antagonist:
`Dolasetron 100 mg PO or 1.8 mg/kg or
`100 mg IV (category 1)
`or
`Granisetron 1-2 mg PO or 1 mg PO bid
`(category 1) or 0.01 mg/kg (maximum 1
`mg) IV or transdermal patch containing
`34.3 mg granisetron applied 24-48 h
`before first dose of chemotherapy
`or
`Ondansetron 16-24 mg PO or 8-12 mg
`(maximum 32 mg/d) IV (category 1)
`or
`Palonosetron 0.25 mg IV (category 1)
`and
`± Lorazepam 0.5-2 mg PO or IV or
`sublingual either every 4 or every 6 h prn
`± H blocker or proton pump inhibitor
`b,c
`d g
`f
`2
`See
`Breakthrough
`Treatment
`(pages 578 and 579)
`Low
`Minimal Nausea/emesis (0–24 h)
`Consider using antiemetics listed under
`primary prophylaxis as treatment for low
`emetogenic-potential drugs
`LOW AND MINIMAL EMETIC RISK CHEMOTHERAPY - EMESIS PREVENTIONb,c
`No routine
`prophylaxis
`See
`Breakthrough
`Treatment
`(pages 578 and 579)
`b
`c
`d
`f
`g
`h 2 2 2
`Antiemetic regimens should be chosen based on the drug with the highest emetic risk and on patient-specific risk factors.
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Fosaprepitant dimeglumine (115 mg) may be substituted for aprepitant (125 mg) 30 minutes before chemotherapy, on day 1 only of the chemotherapy-
`induced nausea and vomiting regimen as an infusion administered over 15 minutes.
`Order of listed antiemetics does not reflect preference.
`Aprepitant should be added (to dexamethasone and a 5-HT3 antagonist regimen) for select patients undergoing other chemotherapies of moderate emetic
`risk (e.g., carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan, methotrexate).
`Data for post-carboplatin ( 300 mg/m , cyclophosphamide 600-1000 mg/m , doxorubicin 50 mg/m ) emesis prevention are category 1.
`Start before chemotherapy
`Dexamethasone 12 mg PO or IV daily
`or
`b,c
`Repeat daily for fractionated doses of chemotherapy
`Metoclopramide 10-40 mg PO or IV either every 4 or every 6 h
`or
`Prochlorperazine 10 mg PO or IV every 4 or every 6 h
`± Lorazepam, 0.5-2 mg PO or IV either every 4 or every 6 h prn
`± H blocker or proton pump inhibitor
`i
`i
`2
`b
`c
`i
`Antiemetic regimens should be chosen based on the drug with the highest emetic risk and on patient-specific risk factors.
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Monitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or every 6 h for dystonic reactions.
`Page 6 of 24
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`
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`578
`Antiemesis Version 3:2009
`Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`All recommendations are category 2A unless otherwise noted.
`No nausea/
`emesis
`Any nausea/
`emesis
`No change in antiemetic regimen
`Continue breakthrough
`medications, on a schedule, not prn
`Consider changing antiemetic therapy to
`higher-level primary treatment
`SUBSEQUENT CYCLESRESPONSE TO BREAKTHROUGH
`ANTIEMETIC TREATMENT
`BREAKTHROUGH TREATMENT FOR CHEMOTHERAPY INDUCED NAUSEA/VOMITING
`Nausea and emesis
`controlled
`Nausea and/or
`emesis uncontrolled
`General principle of breakthrough treatment is to give an additional agent from a different
`drug class prn
`Prochlorperazine 25 mg supp pr every 12 h or 10 mg PO or IV every 4 or 6 h
`or
`Metoclopramide 10-40 mg PO or IV either every 4 or 6 h
`or
`Lorazepam 0.5-2 mg PO either every 4 or 6 h
`or
`i
`i
`Dolasetron 100 mg PO daily or 1.8 mg/kg IV or 100 mg IV
`or
`Ondansetron 16 mg PO or 8 mg IV daily
`or
`Granisetron 1-2 mg PO daily or 1 mg PO bid or 0.01 mg/kg (maximum 1 mg) IV or
`transdermal patch containing 34.3 mg granisetron
`or
`Haloperidol 1-2 mg PO every 4-6 h prn
`or
`Dronabinol 5-10 mg PO either every 3 or 6 h
`or
`Nabilone 1-2 mg PO bid
`or
`Dexamethasone 12 mg PO or IV daily
`or
`Olanzapine 2.5-5 mg PO bid (category 2B)
`or
`Promethazine 12.5-25 mg PO or IV every 4 h
`k
`c
`i
`j
`k
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Monitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or 6 h for dystonic reactions.
`See Principles of Managing Breakthrough Emesis (page 584).
`See blackbox warning/label indication regarding type II diabetes, hyperglycemia, and death in elderly dementia patients.
`c,j
`See Principles of Emesis Control (page 574)
`Page 7 of 24
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`NCCN Clinical Practice Guidelines in Oncology
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`579
`Antiemesis Version 3:2009
`Version 3.2009, 04-01-09 ©2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be
`reproduced in any form without the express written permission of NCCN.
`No nausea/
`emesis
`Any nausea/
`emesis
`No change in antiemetic regimen
`Continue breakthrough
`medications, on a schedule, not prn
`Consider changing antiemetic therapy to
`higher-level primary treatment
`SUBSEQUENT CYCLESRESPONSE TO BREAKTHROUGH
`ANTIEMETIC TREATMENT
`BREAKTHROUGH TREATMENT FOR CHEMOTHERAPY INDUCED NAUSEA/VOMITING
`Nausea and emesis
`controlled
`Nausea and/or
`emesis uncontrolled
`General principle of breakthrough treatment is to give an additional agent from a different
`drug class prn
`Prochlorperazine 25 mg supp pr every 12 h or 10 mg PO or IV every 4 or 6 h
`or
`Metoclopramide 10-40 mg PO or IV either every 4 or 6 h
`or
`Lorazepam 0.5-2 mg PO either every 4 or 6 h
`or
`i
`i
`Dolasetron 100 mg PO daily or 1.8 mg/kg IV or 100 mg IV
`or
`Ondansetron 16 mg PO or 8 mg IV daily
`or
`Granisetron 1-2 mg PO daily or 1 mg PO bid or 0.01 mg/kg (maximum 1 mg) IV or
`transdermal patch containing 34.3 mg granisetron
`or
`Haloperidol 1-2 mg PO every 4-6 h prn
`or
`Dronabinol 5-10 mg PO either every 3 or 6 h
`or
`Nabilone 1-2 mg PO bid
`or
`Dexamethasone 12 mg PO or IV daily
`or
`Olanzapine 2.5-5 mg PO bid (category 2B)
`or
`Promethazine 12.5-25 mg PO or IV every 4 h
`k
`c
`i
`j
`k
`See Principles for Managing Multi-Day Emetogenic Chemotherapy Regimens (page 583).
`Monitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every 4 or 6 h for dystonic reactions.
`See Principles of Managing Breakthrough Emesis (page 584).
`See blackbox warning/label indication regarding type II diabetes, hyperglycemia, and death in elderly dementia patients.
`c,j
`See Principles of Emesis Control (page 574)
`Page 8 of 24
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`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`580
`Antiemesis Version 3:2009
`Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
`All recommendations are category 2A unless otherwise noted.
`EMETOGENIC POTENTIAL OF ANTINEOPLASTIC AGENTS
`AC combination defined as either doxorubicin
`or epirubicin with cyclophosphamide
`Altretamine
`Carmustine > 250 mg/m
`Cisplatin 50 mg/m
`2
`2
`AGENTLEVEL
`Adapted with permission from Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Onc
`1997;15:103-109, and 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.
`High emetic risk
`(> 90% frequency of emesis)l
`Moderate emetic risk
`(30%-90% frequency of emesisl
`Cyclophosphamide > 1500 mg/m
`Dacarbazine
`Mechlorethamine
`Procarbazine (oral)
`Streptozocin
`2
`Aldesleukin > 12-15 million units/m
`Amifostine > 300 mg/m
`Arsenic trioxide
`Azacitidine
`Bendamustine
`Busulfan > 4 mg/d
`Carboplatin
`Carmustine 250 mg/m
`Cisplatin < 50 mg/m
`Cyclophosphamide 1500 mg/m
`Cyclophosphamide (oral)
`Cytarabine > 1 g/m
`Dactinomycin
`Daunorubicin
`2
`2
`2
`2
`2
`2
`Doxorubicin
`Epirubicin
`Etoposide (oral)
`Idarubicin
`Ifosfamide
`Imatinib (oral)
`Irinotecan
`Lomustine
`Melphalan > 50 mg/m
`Methotrexate 250 to > 1000 mg/m
`Oxaliplatin > 75 mg/m
`Temozolomide (oral)
`Vinorelbine (oral)
`m
`2
`2
`2
`l
`m
`Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxis
`Daily use of antiemetics is not recommended based on clinical experience.
`Low emetic risk
`(10%-30% frequency of emesis)l
`Amifostine 300 mg
`Bexarotene
`Capecitabine
`Cytarabine (low dose) 100-200 mg/m
`Docetaxel
`Doxorubicin (liposomal)
`Etoposide
`Fludarabine (oral)
`5-Fluorouracil
`Gemcitabine
`2
`Ixabepilone
`Methotrexate > 50 mg/m < 250 mg/m
`Mitomycin
`Mitoxantrone
`Nilotinib
`Paclitaxel
`Paclitaxel-albumin
`Pemetrexed
`Topotecan
`Vorinostat
`2 2
`Minimal emetic risk
`(< 10% frequency of emesis)l
`Hydroxyurea (oral)
`Lapatinib
`Lenalidomide
`Melphalan (oral low-dose)
`Methotrexate 50 mg/m
`Nelarabine
`Panitumumab
`Pentostatin
`Rituximab
`Sorafenib
`Sunitinib
`Temsirolimus
`Thalidomide
`Thioguanine (oral)
`Trastuzumab
`Valrubicin
`Vinblastine
`Vincristine
`Vinorelbine
`2
`Alemtuzumab
`Alpha Interferon
`Asparaginase
`Bevacizumab
`Bleomycin
`Bortezomib
`Busulfan
`Cetuximab
`Chlorambucil (oral)
`Cladribine (2-chlorodeoxyadenosine)
`Decitabine
`Denileukin diftitox
`Desatinib
`Dexrazoxane
`Erlotinib
`Fludarabine
`Gefitinib
`Gemtuzumab ozogamicin
`EMETOGENIC
`POTENTIAL
`TYPE OF RADIATION THERAPY EMESIS PREVENTION BREAKTHROUGH TREATMENT
`Radiation-induced
`nausea/vomiting
`RT - upper abdomen
`RT - other sites
`Chemotherapy and RT
`Total body irradiation
`None
`Start pretreatment for each day of RT
`treatment:
`Ondansetron 8 mg PO bid-tid
`or
`Granisetron 2 mg PO daily
`± Dexamethasone 2 mg PO tid
`Start pretreatment for each day of RT treatment:
`Ondansetron 8 mg PO bid-tid
`or
`Granisetron 2 mg PO daily, or 3 mg IV daily
`(category 2B)
`± Dexamethasone 2 mg PO tid
`See Breakthrough
`Treatment
`(pages 578 and 579)
`Ondansetron, 8 mg PO bid-tid
`See emesis prevention for chemotherapy-
`induced nausea/vomiting
`(High [page 575], Moderate [page 576], and Low
`[page 577])
`See Principles of Emesis Control (page 574)
`Page 9 of 24
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`NCCN Clinical Practice Guidelines in Oncology
`© Journal of the National Comprehensive Cancer Network | Volume 7 Number 5 | May 2009
`581
`Antiemesis Version 3:2009
`Version 3.2009, 04-01-09 ©2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be
`reproduced in any form without the express written permission of NCCN.
`EMETOGENIC POTENTIAL OF ANTINEOPLASTIC AGENTS
`AC combination defined as either doxorubicin
`or epirubicin with cyclophosphamide
`Altretamine
`Carmustine > 250 mg/m
`Cisplatin 50 mg/m
`2
`2
`AGENTLEVEL
`Adapted with permission from Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Onc
`1997;15:103-109, and 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.
`High emetic risk
`(> 90% frequency of emesis)l
`Moderate emetic risk
`(30%-90% frequency of emesisl
`Cyclophosphamide > 1500 mg/m
`Dacarbazine
`Mechlorethamine
`Procarbazine (oral)
`Streptozocin
`2
`Aldesleukin > 12-15 million units/m
`Amifostine > 300 mg/m
`Arsenic trioxide
`Azacitidine
`Bendamustine
`Busulfan > 4 mg/d
`Carboplatin
`Carmustine 250 mg/m
`Cisplatin < 50 mg/m
`Cyclophosphamide 1500 mg/m
`Cyclophosphamide (oral)
`Cytarabine > 1 g/m
`Dactinomycin
`Daunorubicin
`2
`2
`2
`2
`2
`2
`Doxorubicin
`Epirubicin
`Etoposide (oral)
`Idarubicin
`Ifosfamide
`Imatinib (oral)
`Irinotecan
`Lomustine
`Melphalan > 50 mg/m
`Methotrexate 250 to > 1000 mg/m
`Oxaliplatin > 75 mg/m
`Temozolomide (oral)
`Vinorelbine (oral)
`m
`2
`2
`2
`l
`m
`Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxis
`Daily use of antiemetics is not recommended based on clinical experience.
`Low emetic risk
`(10%-30% frequency of emesis)l
`Amifostine 300 mg
`Bexarotene
`Capecitabine
`Cytarabine (low dose) 100-200 mg/m
`Docetaxel
`Doxorubicin (liposomal)
`Etoposide
`Fludarabine (oral)
`5-Fluorouracil
`Gemcitabine
`2
`Ixabepilone
`Methotrexate > 50 mg/m < 250 mg/m
`Mitomycin
`Mitoxantrone
`Nilotinib
`Paclitaxel
`Paclitaxel-albumin
`Pemetrexed
`Topotecan
`Vorinostat
`2 2
`Minimal emetic risk
`(< 10% frequency of emesis)l
`Hydroxyurea (oral)
`Lapatinib
`Lenalidomide
`Melphalan (oral low-dose)
`Methotrexate 50 mg/m
`Nelarabine
`Panitumumab
`Pentostatin
`Rituximab
`Sorafenib
`Sunitinib
`Temsirolimus
`Thalidomide
`Thioguanine (oral)
`Trastuzumab
`Valrubicin
`Vinblastine
`Vincristine
`Vinorelbine
`2
`Alemtuzumab
`Alpha Interferon
`Asparaginase
`Bevacizumab
`Bleomycin
`Bortezomib
`Busulfan
`Cetuximab
`Chlorambucil (oral)
`Cladribine (2-chlorodeoxyadenosine)
`Decitabine
`Denileukin diftitox
`Desatinib
`Dexrazoxane
`Erlotinib
`Fludarabine
`Gefitinib
`Gemtuzumab ozogamicin
`EMETOGENIC
`POTENTIAL
`TYPE OF RADIATION THERAPY EMESIS PREVENTION BREAKTHROUGH TREATMENT
`Radiation-induced
`nausea/vomiting
`RT - upper abdomen
`RT - other sites
`Chemotherapy and RT
`Total body irradiation
`None
`Start pretreatment for each day of RT
`treatment:
`Ondansetron 8 mg PO bid-tid
`or
`Granisetron 2 mg PO daily
`± Dexamethasone 2 mg PO tid
`Start pretreatment for each day of RT treatment:
`Ondansetron 8 mg PO bid-tid
`or
`Granisetron 2 mg PO daily, or 3 mg IV daily
`(category 2B)
`± Dexamethasone 2 mg PO tid
`See Breakthrough
`Treatment
`(pages 578 and 579)
`Ondansetron, 8 mg PO bid-tid
`See emesis prevention for chemotherapy-
`induced nausea/vomiting
`(High [page 575], Moderate [page 576], and Low
`[page 577])
`See Principles of Emesis Control (page 574)
`Page 10 of 24
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`© Journal of