Overview of the updated antiemetic guidelines for chemotherapy-induced nausea and vomiting

nausea and vomitingRudolph M. Navari, MD, PhDIndiana University School of Medicine–South Bend, South Bend, IN Nausea and vomiting associated with cancer chemotherapy are experienced by 70%–80% of patients receiving chemotherapy and can result in significant morbidity. Chemotherapy-induced nausea and vomiting (CINV) adversely affects patient quality of life, often leading to poor compliance with the treatment regimen and serious metabolic complications. Several classes of antiemetic drugs are available to prevent or treat CINV. Older agents include phenothiazines, antihistamines, and corticosteroids. Serotonin (5-HT3) receptor antagonists became available in the 1990s for use in preventing CINV. Recently, the NK1 receptor antagonist aprepitant was introduced for use in combination therapy regimens. Despite this introduction of new and more effective antiemetic agents, emesis remains a significant complication of chemotherapy. Updated antiemetic guidelines were published in 2007 by the National Comprehensive Cancer Network and in 2006 by the American Society of Clinical Oncology. Updates for clinicians who treat patients with CINV are now available and are reviewed here.
C hemotherapy-induced nausea wound dehiscence.1,11 Patients who are dehydrated, debilitated, or malnourished, as well as those who have an electrolyte imbalance or those who have re- cently undergone surgery or radiation therapy, are at greater risk of experiencing serious complications dergoing chemotherapy experience emesis, with Despite the recent introduction of new and 10%–44% experiencing anticipatory emesis.1,2 more effective antiemetic agents, emesis remains CINV results in significant morbidity and neg- a significant complication of chemotherapy. Up- atively impacts patient quality of life.3–5 CINV dated antiemetic guidelines were published in 2007 may cause nonadherence to chemotherapy or by the National Comprehensive Cancer Network dose reductions due to anticipatory nausea and (NCCN) and in 2006 by the American Society of Increased risk of CINV is associated with the Manuscript received February 15, 2007; accepted March 1, following factors: age < 50 years, female gender, vomiting during previous chemotherapy, preg- Funding for this publication was provided by Roche Labora- nancy-induced nausea/vomiting, history of mo- Correspondence to: Rudolph M. Navari, MD, PhD, Professor tion sickness, and anxiety.9,10 CINV can result in of Medicine, Assistant Dean, and Director, Indiana University weakness, weight loss, electrolyte imbalance, dehy- School of Medicine–South Bend, 100 Raclin-Carmichael Hall, dration, or anorexia and is associated with a variety 1234 Notre Dame Avenue, South Bend, IN 46617; telephone: of complications, including fractures, esophageal 574-631-3793; fax: 574-631-4939; e-mail: rnavari@nd.edu. tears, decline in behavioral and mental status, and Commun Oncol 2007;4(suppl 1):3–11 2007 Elsevier Inc. Al rights reserved.
Pathophysiology of
nausea and vomiting
Types, causes, and risk
categories of CINV
derly patients (> 65 years of age) are or requires “rescue” is called break- 4 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting TABLE 1
Emetic risk of antineoplastic agents
High emetic risk
Moderate emetic risk
Low emetic risk
Minimal emetic risk
(> 90% frequency
(30%–90% frequency
(10%–30% frequency
(< 10% frequency of
of emesis)*
of emesis)*
of emesis)*
* Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxis† Daily use of antiemetics is not recommended based on clinical experienceAdapted, with permission from the American Society of Clinical Oncology,19 with additional information.1 Principles in the
management of CINV
unless specifically stated.1,17 The 2006 forth several principles of effective an- dition to patient-specific risk factors.
emetic risk (the risk of emesis persists Antiemetic agents
Antiemetic recommendations by emetic-risk categories Emetic-risk category
ASCO guidelines
NCCN guidelines
Three-drug combination of a 5-HT3 receptor Before chemotherapy, a 5-HT3 receptor antagonist antagonist, dexamethasone, and aprepitant (ondansetron, granisetron, dolasetron, or palono- setron*), dexamethasone (12 mg), and aprepitant (125 mg) recommended, with or without lorazepam For patients receiving cisplatin and all other For prevention of delayed emesis, dexamethasone agents of high emetic risk, the two-drug (8 mg) on days 2–4 plus aprepitant (80 mg) on combination of dexamethasone and aprepitant days 2 and 3 recommended, with or without recommended for prevention of delayed emesis For patients receiving an anthracycline and For patients receiving an anthracycline and cyclophosphamide, the three-drug combination cyclophosphamide and selected patients receiving a 5-HT3 receptor antagonist, dexamethasone, and other chemotherapies of moderate emetic risk (eg, aprepitant recommended before chemotherapy; carboplatin, cisplatin, doxorubicin, epirubicin, single-agent aprepitant recommended on days 2 ifosfamide, irinotecan, or methotrexate), a 5-HT3 receptor antagonist (ondansetron, granisetron, For patients receiving other chemotherapies of dolasetron, or palonosetron*), dexamethasone moderate emetic risk, the two-drug combination of (12 mg), and aprepitant (125 mg) recommended, a 5-HT3 receptor antagonist and dexamethasone with or without lorazepam, before chemotherapy; recommended before chemotherapy; single-agent for other patients, aprepitant is not recommended dexamethasone or a 5-HT3 receptor antagonist For prevention of delayed emesis, dexamethasone suggested on days 2 and 3 for prevention of (8 mg) or a 5-HT3 receptor antagonist on days 2–4 or, if used on day 1, aprepitant (80 mg) on days 2 and 3, with or without dexamethasone (8 mg) on days 2–4, recommended, with or without Dexamethasone (8 mg) suggested; no routine Metoclopramide, with or without diphenhydramine; preventive use of antiemetics for delayed emesis dexamethasone (12 mg); or prochlorperazine No antiemetic administered routinely before or No routine prophylaxis; consider using antiemetics listed under primary prophylaxis as treatment * Order of listed antiemetics does not reflect preferenceASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network; 5-HT3 = 5-hydroxytryptamineAdapted, with permission, from the American Society of Clinical Oncology18 Reproduced and adapted with permission from the NCCN 1.2007 Antiemesis Guidelines.1 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the guideline, go online to www.nccn.org.
Intravenous (IV)
* The FDA-approved IV dose of granisetron is 0.01 mg/kg.
Adapted, with permission, from the American Society of Clinical 6 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting Efficacy and safety
of antiemetic agents
in clinical trials
Pharmacologic management
by emetogenic potential
the historic control group (0%; P < 8 COMMUNITY ONCOLOGY ■ April 2007
Updated antiemetic guidelines for chemotherapy-induced nausea and vomiting References
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nausea and vomiting in patients with breast with ondansetron in preventing chemother- cancer after moderately emetogenic chemo- Affiliation: Dr. Navari is Professor of Medicine, Assistant Dean, and Director, Indiana Univer- apy-induced nausea and vomiting following therapy. J Clin Oncol 2005;23:2822–2830.
sity School of Medicine–South Bend, South role of psychological variables in post-che- Conflicts of interest: None disclosed.
motherapy nausea: anxiety and expectation. April 2007 ■ COMMUNITY ONCOLOGY 11

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