NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Antiemesis Version 1.2015 NCCN.org Continue Version 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, 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 Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Panel Members Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion David S Ettinger, MD/Chair † The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Steve Kirkegaard, PharmD Huntsman Cancer Institute at the University of Utah Eric Roeland, MD UC SanDiego Moores Cancer Center Michael J Berger, PharmD/Vice Chair, BCOP The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute Dwight D Kloth, PharmD, BCOP Fox Chase Cancer Center Hope S Rugo, MD † ‡ UCSF Helen Diller Family Comprehensive Cancer Center Sally Barbour, PharmD, BCOP, CCP Duke Cancer Institute Philip J Bierman, MD † ‡ Fred & Pamela Buffet Cancer Center Debra Brandt, DO Yale Cancer Center/Smilo Cancer Hospital Dawn E Dolan, PharmD, BCOP Mofitt Cancer Center Georgiana Ellis, MD † Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance Eun Jeong Kim, PharmD, MS Stanford Cancer Institute Mark G Kris, MD † Memorial Sloan-Kettering Cancer Center Dean Lim, MD † City of Hope Comprehensive Cancer Center Cynthia Ma, MD, PhD † Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine Belinda Mandrell, PhD, RN † St Jude Children’s Research Hospital/ University of Tennessee Cancer Institute Barbara Todaro, PharmD Roswell Park Cancer Institute Susan G Urba, MD † £ University of Michigan Comprehensive Cancer Center Laura Boehnke Michaud, PharmD, BCOP The University of Texas M.D Anderson Cancer Center Lisle M Nabell, MD University of Alabama at Birmingham Comprehensive Cancer Center Kim Noonan, MS, RN, ANP, AOCN # Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center NCCN Fayna Ferkle, PharmD Miranda Hughes, PhD Dorothy A Shead, MS NCCN Guidelines Panel Disclosures Bridget Scullion, PharmD, BCOP Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center Continue ‡ Hematology/hematology oncology Þ Internal medicine † Medical oncology # Nurse Pharmacology £ Supportive care including palliative, pain management, pastoral care, and oncology social work * Writing committee member Version 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, 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 Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Table of Contents Antiemesis NCCN Antiemesis Panel Members Guidelines Updates Principles of Emesis Control for the Cancer Patient (AE-1) CHEMOTHERAPY-INDUCED EMESIS: High Emetic Risk Intravenous Chemotherapy Acute and Delayed Emesis Prevention (AE-2) Moderate Emetic Risk Intravenous Chemotherapy - Emesis Prevention (AE-3) Low and Minimal Emetic Risk Intravenous Chemotherapy - Emesis Prevention (AE-4) Oral Chemotherapy - Emesis Prevention (AE-5) Breakthrough Treatment for Chemotherapy-Induced Nausea/Vomiting (AE-6) Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7) Emetogenic Potential of Oral Antineoplastic Agents (AE-9) Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A) Principles for Managing Breakthrough Emesis (AE-B) NCCN Guidelines Index Antiemesis Table of Contents Discussion Clinical Trials: NCCN believes that the best management for any cancer patient is in a clinical trial Participation in clinical trials is especially encouraged To ind clinical trials online at NCCN member institutions, click here: nccn.org/clinical_trials/physician.html NCCN Categories of Evidence and Consensus: All recommendations are Category 2A unless otherwise speciied See NCCN Categories of Evidence and Consensus RADIATION-INDUCED EMESIS: Radiation-Induced Emesis Prevention/Treatment (AE-10) ANTICIPATORY EMESIS: Anticipatory Emesis Prevention/Treatment (AE-11) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network® All rights reserved The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN ©2015 Version 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, 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 Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines® Version 1.2015 Updates Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion Updates in Version 1.2015 of the NCCN Guidelines for Antiemesis from Version 2.2014 include: AE-2 • The information on this page has been reformatted for clarity and consistency • High emetic risk intravenous chemotherapy - acute and delayed emesis prevention: Removed “Preferred” from palonosetron 0.25 mg IV day Day 1, added the following netupitant-containing regimen: ◊ Netupitant 300 mg/palonosetron 0.5 mg PO once ◊ Dexamethasone 12 mg PO day ◊ Hesketh P, Rossi G, Rizzi G et al Eficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose ranging pivotal study Ann Oncol 2014; 25: 1340–1346 Changed lorazepam from every 4-6 h to every h (also applies to AE-3 and AE-6) Added a new footnote, “If neither aprepitant nor fosaprepitant are given on day 1, then dexamethasone 20 mg PO/IV once on day 1, followed by mg BID PO/IV on days 2, 3, AE-3 • Moderate emetic risk intravenous chemotherapy - emesis prevention: Day 1, added the following netupitant-containing regimen: ◊ Netupitant 300 mg/palonosetron 0.5 mg PO once ◊ Dexamethasone 12 mg PO day ◊ Aapro M, Rugo H, Rossi G, et al A randomized phase III study evaluating the eficacy and safety of NEPA, a ixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy Ann Oncol 2014;25:1328-1333 Changed olanzapine from days 2, 3, to days 2, Modiied footnote “m”: As per high emetic risk prevention, aprepitant or fosaprepitant should be added (to dexamethasone and a 5-HT3 antagonist regimen) for select patients with additional risk factors or who have failed previous therapy with a steroid + 5HT3 antagonist alone (See AE-2) Added a new footnote, “No further therapy required if palonosetron or granisetron patch given on day 1.” AE-5 • Oral chemotherapy - emesis prevention: High to moderate emetic risk, clariied ondansetron 16-24 mg (total dose) PO daily Low to minimal emetic risk, clariied ◊ Dolasetron 100 mg PO daily added “PRN” ◊ Granisetron 1-2 mg (total dose) PO added “PRN” ◊ Ondansetron 8-16 mg (total dose) PO daily added “PRN” AE-8 • Emetogenic potential of Intravenous antineoplastic agents Added the following agents to low emetic risk: ◊ Belinostat ◊ Blinatumomab Added the following agents to minimal emetic risk: ◊ Nivolumab ◊ Obinutuzumab ◊ Pembrolizumab ◊ Ramucirumab ◊ Siltuximab AE-9 • Emetogenic potential of oral antineoplastic agents Added the following agents to moderate to high emetic risk: ◊ Ceritinib ◊ Lenvatinib ◊ Olaparib ◊ Panobinostat Added the following agents to minimal to low emetic risk: ◊ Afatinib ◊ Ibrutinib ◊ Idelalisib ◊ Palbociclib AE-11 • Anticipatory emesis prevention treatment, modiied the following recommendation “Consider anxiolytic therapy: ◊ For example, alprazolam 0.5-1 mg or lorazepam 0.5-2 mg PO TID beginning on the night before treatment and then repeated the next day 1-2 hours before chemotherapy begins AE-A • Principles of managing multiday emetogenic chemotherapy regimens: Included “transdermal” as an optional route of administration for antiemetic regimens Version 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® UPDATES Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion 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 days for high and days for moderate after the last dose of chemotherapy Patients need to be protected throughout the full period of risk • Oral and intravenous 5-HT3 antagonists have equivalent eficacy when used at the appropriate doses • Consider the toxicity of the speciic antiemetic(s) • Choice of antiemetic(s) used should be based on the emetic risk of the therapy, prior experience with antiemetics, and patient factors • There are other potential causes of emesis in cancer patients These may include: Partial or complete bowel obstruction Vestibular dysfunction Brain metastases Electrolyte imbalance: hypercalcemia, hyperglycemia, or hyponatremia Uremia Concomitant drug treatments, including opiates Gastroparesis: tumor or chemotherapy (eg, vincristine) induced or other causes (eg, diabetes) Psychophysiologic: ◊ Anxiety ◊ Anticipatory nausea/vomiting • For use of antiemetics for nausea/vomiting that are not related to radiation and/or chemotherapy, see NCCN Guidelines for Palliative Care • For multi-drug regimens, select antiemetic therapy based on the drug with the highest emetic risk See Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7) • Consider using an H2 blocker or proton pump inhibitor to prevent dyspepsia, which can mimic nausea • Lifestyle measures may help to alleviate nausea/vomiting, such as eating small frequent meals, choosing healthful foods, controlling the amount of food consumed, and eating food at room temperature A dietary consult may also be useful See NCI’s “Eating Hints: Before, During, and After Cancer Treatment.” (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 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® AE-1 Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion HIGH EMETIC RISK INTRAVENOUS CHEMOTHERAPY - ACUTE AND DELAYED EMESIS PREVENTIONa,b DAY 1: Select option A, B, or C (order does not imply preference) DAYS 2, 3, 4: Start before chemotherapy:c A: regimen:d select Aprepitant-containing groups (category 1): • Neurokinin-1 (NK1) antagonist: Aprepitant 125 mg PO once Fosaprepitant 150 mg IV once A:k one agent from each of the following If aprepitant PO given day 1, aprepitant 80 mg PO daily on days 2, If fosaprepitant IV given on day 1, no further aprepitant is needed on days 2, AND AND • Serotonin (5-HT3) antagonist:e Dolasetron 100 mg PO once Granisetron mg PO once, or mg PO BID, or 0.01 mg/kg (max mg) IV once, or 3.1 mg/24 h transdermal patch applied 24-48 h prior to irst dose of chemotherapy Ondansetron 16-24 mg PO once or 8-16 mg IV oncef See Palonosetron 0.25 mg IV onceg If aprepitant PO given day 1, dexamethasone mg PO/ Breakthrough AND Treatment (AE-6) h,l IV daily days 2, 3, 4l • Steroid: If fosaprepitant IV given on day 1, dexamethasone mg Dexamethasone 12 mg PO/IV once PO/IV once on day 2, then mg PO/IV BID days 3, 4l B: B: Netupitant-containing regimen:d,i Netupitant 300 mg/palonosetron 0.5 mg PO once Dexamethasone 12 mg PO/IV once Dexamethasone mg PO/IV daily on days 2, 3, C: C: Olanzapine-containing regimen:d,j Olanzapine 10 mg PO once Palonosetron 0.25 mg IV once Dexamethasone 20 mg IV once aSee Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7) bAntiemetic regimens should be chosen based on the drug with the highest specific risk factors cSee Principles of Managing Multiday Emetogenic Chemotherapy dWith or without lorazepam 0.5-2 mg PO or IV or sublingual every Olanzapine 10 mg PO daily on days 2, 3, emetic risk as well as patient- Regimens (AE-A) hours as needed days 1-4 With or without H2 blocker or proton pump inhibitor See Principles of Emesis Control for the Cancer Patient (AE-1) eSerotonin (5-HT3) antagonists may increase the risk of developing prolongation of the QT interval of the electrocardiogram See Discussion fThe FDA recommends a maximum of 16 mg for a single dose of IV ondansetron gData with palonosetron are based on randomized studies in combination with steroids only hUse of steroids is contraindicated with drugs such as interleukin-2 (ie, IL-2, aldesleukin) iHesketh PJ, Rossi G, Rizzi G, et al Eficacy and safety of NEPA, an oral combination of and interferon netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose ranging pivotal study Ann Oncol 2014;25:1340-1346 jNavari RM, Gray SE, Kerr AC Olanzapine versus aprepitant for the prevention of chemotherapyinduced nausea and vomiting: a randomized phase III trial J Support Oncol 2011;9:188-195 kSome NCCN Member Institutions use a 5-HT3 antagonist (unless palonosetron or granisetron patch given on day 1) on days 2, 3, in addition to steroid ± apprepitant l If neither aprepitant nor fosaprepitant are given on day 1, then dexamethasone 20 mg PO/IV once on day 1, followed by mg BID PO/IV on days 2, 3, 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 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® AE-2 Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion MODERATE EMETIC RISK INTRAVENOUS CHEMOTHERAPY - ACUTE AND DELAYED EMESIS PREVENTIONa,b DAY 1: Select option A, B, or C (order does not imply preference) Start before chemotherapy:c DAYS and 3: A: A: Serotonin (5-HT3) antagonist + steroid (category 1) ± NK-1 antagonistd • Serotonin (5-HT3) antagonist (Select one):e Dolasetron 100 mg PO once Granisetron mg PO once, or mg PO BID, or 0.01 mg/kg (max mg) IV once, or 3.1 mg/24 h transdermal patch applied 24-48 h prior to irst dose of chemotherapy Ondansetron 16-24 mg PO once or 8-16 mg IV oncef Palonosetron 0.25 mg IV onceg (preferred) AND • Steroid:h Dexamethasone 12 mg PO/IV once WITH/WITHOUT • Neurokinin-1 (NK1) antagonist:m Aprepitant 125 mg PO once Fosaprepitant 150 mg IV once B: Netupitant-containing regimen:d,n Netupitant 300 mg/palonosetron 0.5 mg PO once Dexamethasone 12 mg PO/IV once C: Olanzapine-containing regimen:d,j Olanzapine 10 mg PO once Palonosetron 0.25 mg IV once Dexamethasone 20 mg IV once • Serotonin (5-HT3) antagonist monotherapyo (Select one):e Dolasetron 100 mg PO daily on days 2, Granisetron 1-2 mg PO daily or mg PO BID or 0.01 mg/kg (maximum mg) IV daily on days 2, Ondansetron mg PO BID or 16 mg PO daily or 8-16 mg IV daily on days 2, 3f OR • Steroid monotherapy:h Dexamethasone mg PO/IV daily on days 2, OR • NK1 antagonist ± steroid: h,m,l Aprepitant used day 1: Aprepitant 80 mg PO daily on days 2, ± dexamethasone mg PO/IV daily on days 2, Fosaprepitant used day 1: ± dexamethasone mg PO or IV daily on days 2, B: See Breakthrough Treatment (AE-6) ± Dexamethasone mg PO/IV daily on days 2, C: Olanzapine 10 mg PO daily days 2, RM, Gray SE, Kerr AC Olanzapine versus aprepitant for the prevention of chemotherapyinduced nausea and vomiting: a randomized phase III trial J Support Oncol 2011;9:188-195 If neither aprepitant nor fosaprepitant are given on day 1, dexamethasone 20 mg PO/IV once on day 1, specific risk factors cSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A) followed by mg BID PO/IV on days 2, 3, mAs per high emetic risk prevention, aprepitant or fosaprepitant should be added (to dexamethasone dWith or without lorazepam 0.5-2 mg PO or IV or sublingual every hours as needed days 1-4 and a 5-HT3 antagonist regimen) for select patients with additional risk factors or who have failed With or without H2 blocker or proton pump inhibitor See Principles of Emesis Control for the Cancer previous therapy with a steroid + 5HT3 antagonist alone (See AE-2) Patient (AE-1) eSerotonin (5-HT3) antagonists may increase the risk of developing prolongation of the QT interval of the nAapro M, Rugo H, Rossi G, et al A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapyelectrocardiogram See Discussion fThe FDA recommends a maximum of 16 mg for a single dose of IV ondansetron induced nausea and vomiting following moderately emetogenic chemotherapy Ann Oncol gData with palonosetron are based on randomized studies in combination with steroids only 2014;25:1328-1333 hUse of steroids is contraindicated with drugs such as interleukin-2 (ie, IL-2, aldesleukin) and interferon o No further therapy required if palonsetron or granisetron patch given on day 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 aSee Emetogenic Potential of Intravenous Antineoplastic Agents (AE-7) bAntiemetic regimens should be chosen based on the drug with the highest emetic risk as well as patient- jNavari l Version 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® AE-3 Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion LOW AND MINIMAL EMETIC RISK INTRAVENOUS CHEMOTHERAPY - EMESIS PREVENTIONb,c,p Low Minimal Start before chemotherapy (order does not imply preference) b,c,d Repeat daily for multiday doses of chemotherapy Dexamethasone 12 mg PO/IV dailyh or Metoclopramide 10-40 mg PO/IV and then either every or every h PRNq or Prochlorperazine 10 mg PO/IV and then every h PRN (maximum 40 mg/day)q or Serotonin (5-HT3) antagoniste (select one): ◊ Dolasetron 100 mg PO daily ◊ Granisetron 1-2 mg (total dose) PO daily ◊ Ondansetron 8-16 mg PO daily Breakthrough Treatment for Chemotherapy-Induced Nausea/Vomiting (AE-6) No routine prophylaxis bAntiemetic regimens should be chosen based on the drug with the highest emetic risk as well as cSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A) dWith or without lorazepam 0.5-2 mg PO or IV or sublingual every hours as needed days 1-4 patient-specific risk factors With or without H2 blocker or proton pump inhibitor See Principles of Emesis Control for the Cancer Patient (AE-1) eSerotonin (5-HT3) antagonist may increase the risk of developing prolongation of the QT interval of the electrocardiogram See Discussion hUse of steroids is contraindicated with drugs such as interleukin-2 (ie, IL-2, aldesleukin) and interferon pSee Emetogenic Potential of Intravenous Antineoplastic Agents (AE-8) qMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every or every h for dystonic reactions If allergic to diphenhydramine, benztropine at 1-2 mg IV or IM x dose, followed by oral dose of 1-2 mg daily or BID if needed to control the reaction use 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 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® AE-4 Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis NCCN Guidelines Index Antiemesis Table of Contents Discussion ORAL CHEMOTHERAPY - EMESIS PREVENTIONb,c,r,s High to moderate emetic risk Low to minimal emetic risk Start before chemotherapy and continue daily (order does not imply preference)d • Serotonin (5-HT3) antagonist (Choose one):e Dolasetron 100 mg PO daily Granisetron 1-2 mg (total dose) PO daily Ondansetron 16-24 mg (total dose) PO daily PRN recommended Nausea/ vomiting Breakthrough Treatment for Chemotherapy-Induced Nausea/Vomiting (AE-6) Start before chemotherapy and continue daily (order does not imply preference)d Metoclopramide 10-40 mg PO and then every or every h PRNq or Prochlorperazine 10 mg PO and then every h PRN (maximum 40 mg/day)q or Haloperidol 1-2 mg PO every or every h PRNq or Serotonin (5-HT3) antagonist (Choose one):e ◊ Dolasetron 100 mg PO daily PRN ◊ Granisetron 1-2 mg (total dose) PO daily PRN ◊ Ondansetron 8-16 mg (total dose) PO daily PRN qMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every or every h for dystonic reactions If allergic to diphenhydramine, use bAntiemetic regimens should be chosen based on the drug with the highest emetic benztropine at 1-2 mg IV or IM x dose, followed by oral dose of 1-2 mg daily or risk as well as patient-specific risk factors BID if needed to control the reaction cSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A) rSee Emetogenic Potential of Oral Antineoplastic Agents (AE-9) dWith or without lorazepam 0.5-2 mg PO or IV or sublingual every hours as sThese antiemetic recommendations apply to oral chemotherapy only When needed days 1-4 With or without H2 blocker or proton pump inhibitor combined with IV agents in a combination chemotherapy regimen, the antiemetic See Principles of Emesis Control for the Cancer Patient (AE-1) recommendations for the agent with the highest level of emetogenicity should eSerotonin (5-HT3) antagonists may increase the risk of developing prolongation of be followed If multiple oral agents are combined, emetic risk may increase and the QT interval of the electrocardiogram See Discussion require 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 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® AE-5 Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis BREAKTHROUGH TREATMENT FOR CHEMOTHERAPY-INDUCED NAUSEA/VOMITING c,t The general principle of breakthrough treatment is to add one agent from a different drug class to the current regimen (order does not imply preference) • Atypical antipsychotic: Olanzapine 10 mg PO daily for daysu • Benzodiazepine: Lorazepam 0.5-2 mg PO/SL/IV every h • Cannabinoid: Dronabinol 5-10 mg PO every 3-6 h Nabilone 1-2 mg PO BID • Other: Haloperidol 0.5-2 mg PO/IV every 4-6 hq Any Metoclopramide 10-40 mg PO/IV every 4-6 hq nausea/ vomiting Scopolamine transdermal patch patch every 72 h • Phenothiazine: Prochlorperazine 25 mg supp pr every 12 h or 10 mg PO/IV every hq Promethazine 25 mg supp pr every h or 12.5-25 mg PO/IV (central line only) every 4-6 hq • Serotonin 5-HT3 antagonists:e Dolasetron 100 mg PO daily Granisetron 1-2 mg PO daily or mg PO BID or 0.01 mg/kg (maximum mg) IV daily Ondansetron 16 mg PO/IV daily • Steroid: Dexamethasone 12 mg PO/IV daily NCCN Guidelines Index Antiemesis Table of Contents Discussion RESPONSE TO BREAKTHROUGH ANTIEMETIC TREATMENT Nausea and vomiting controlled SUBSEQUENT CYCLES Continue breakthrough medications, on a schedule, not PRN Consider changing antiemetic therapy to higher level primary treatment for next cycle Nausea and/ or vomiting uncontrolled Re-evaluate and consider dose adjustments and/or switching to a different therapy cSee Principles of Managing Multiday Emetogenic Chemotherapy Regimens (AE-A) eSerotonin (5-HT3) antagonists may increase the risk of developing prolongation of the QT interval of the electrocardiogram See Discussion qMonitor for dystonic reactions; use diphenhydramine 25-50 mg PO or IV either every or every h for dystonic reactions If allergic to diphenhydramine use benztropine at 1-2 mg IV or IM x dose, followed by oral dose of 1-2 mg daily or BID if needed to control the reaction tSee Principles of Managing Breakthrough Treatment (AE-B) uNavari RM, Nagy CK, Gray SE The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy Support Care Cancer 2013;21:1655-1663 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 1.2015, 04/01/15 © National Comprehensive Cancer Network, Inc 2015, All rights reserved The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® AE-6 Printed by Helena Hedejova on 4/3/2015 4:42:28 AM For personal use only Not approved for distribution Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved NCCN Guidelines Version 1.2015 Antiemesis on days to (51%) and on days to (83%); the most common adverse events were mild headache and constipation.167 A recent study assessed palonosetron given for 1, 2, or days in combination with dexamethasone for patients receiving multiday high-dose chemotherapy prior to stem cell transplantation for multiple myeloma (N=73); during the 7-day emesis prevention period, about 40-45% of patients had no emesis (with no differences observed between palonosetron treatment groups), and no serious adverse events were reported However, even among the patients who received either or days of palonosetron, only 20% had a complete response (ie, emesis free without rescue medication).168 Another study found that a palonosetron/dexamethasone regimen appeared to be more effective for multiday chemotherapy than an ondansetron/dexamethasone regimen; patients received a second dose of palonosetron for breakthrough emesis, which was effective in 67% of patients who experienced nausea or vomiting.164 Further studies are needed to define whether a need exists for repeat dosing of palonosetron in the setting of multiday chemotherapy The potential role of NK-1 antagonists in the antiemetic management of multiday chemotherapy regimens has been investigated in several studies In one study, the addition of the NK-1 antagonist aprepitant to granisetron and dexamethasone was evaluated in patients receiving multiday high and moderate emetogenic chemotherapy (N=78); in this study, the 3-drug antiemetic regimen was given during chemotherapy, and aprepitant and dexamethasone was given for an additional days following chemotherapy.169 CR (during the time period from day until days after chemotherapy) was observed in 58% and 73% of patients who received high and moderate emetogenic regimens, respectively.169 In a recent multicenter phase II study, an extended 7-day regimen with aprepitant (125 mg PO day 1, 80 mg PO days 2–7) combined with a 5HT3 receptor antagonist (days 1–5) and dexamethasone (8 mg PO NCCN Guidelines Index Antiemesis Table of Contents Discussion days 1–8) was evaluated in patients with germ line tumors undergoing chemotherapy cycles with 5-day cisplatin-based regimens (N=50).170 During cycle of chemotherapy, 96% of patients had no emesis on day and 82% had no emesis during days to In addition, 71% had no nausea on day of cycle 1, and 27% had no nausea during days to Over 80% of patients had no emesis on any given day of any given chemotherapy cycle No unexpected or serious adverse events were reported.170 In a recent double-blind, randomized, placebo-controlled phase III cross-over trial, the efficacy of adding aprepitant (versus placebo) to an antiemetic regimen with 5-HT3 receptor antagonist and dexamethasone was evaluated in patients with testicular cancer undergoing cycles of a 5-day cisplatin combination chemotherapy regimen (N=71; n=69 evaluable).171 Patients were randomized to receive aprepitant (125 mg PO day 3, 80 mg PO days 4–7) or placebo, combined with a 5-HT3 antagonist (days 1–5) and dexamethasone (20 mg days 1, 2) during the first cycle, and then crossed over to the opposite antiemetic regimen during the second cycle of chemotherapy Thus, patients served as their own controls after receiving either aprepitant or placebo for cycle Palonosetron was excluded from the options for 5-HT3 antagonists due to its longer half-life.171 The primary endpoint of the study was CR (no emetic episodes and no rescue medication) during the overall study period (days 1–8) The CR rate for the overall study period was significantly higher with aprepitant compared with placebo (42% vs 13%; P