• Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006 Jun 20;24(18):1-16. [110 references]

This is the current release of the guideline.

This guideline updates a previous version: American Society of Clinical Oncology. Recommendations for the use of antiemetics: Evidence-based, clinical practice guidelines. J Clin Oncol 1999 Sep;17(9):2971.

Nausea and vomiting associated with chemotherapy and radiotherapy for cancer

Management
Prevention
Risk Assessment
Treatment

Oncology
Pediatrics

Physicians

To update the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology

Adult and pediatric patients with cancer receiving chemotherapy or radiation therapy

1. Assessment of patient's risk for emesis
2. Antiemetic pharmacotherapy:
   • Agents with the highest therapeutic index:
     • Serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists
     • Corticosteroids (dexamethasone and methylprednisolone)  (Note: dexamethasone is the recommended agent)
     • Neurokinin-1 (NK₁) receptor antagonists (aprepitant)
   • Agents of lower therapeutic index (not recommended but reserved for patients with intolerance to 5-HT₃):
     • Dopamine antagonists (metoclopramide)
     • Butyrophenones, phenothiazines, and cannabinoids
   • Adjunctive drugs, including benzodiazepines (lorazepam , alprazolam) and antihistamines (diphenhydramine)
   • Combinations of antiemetics: serotonin antagonists with corticosteroids and aprepitant

• Control of emesis (vomiting), measured by counting the number of vomiting episodes
• Control of nausea (perception that emesis may occur), as judged by the patient

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases
Searches of Unpublished Data

For the 2006 update, a methodology similar to that applied in the original American Society of Clinical Oncology practice guideline for antiemetics was used. Pertinent information published from 1998 through February 2006 was reviewed. The MEDLINE database (National Library of Medicine, Bethesda, MD) was searched to identify relevant information from the published literature for this update. A series of searches was conducted using the medical subject headings or text words "vomiting," "nausea," "neoplasms," "cancer," "tumor," "tumor," and "malignant." These terms were combined with a range of medical subject headings and text words representing available antiemetics agents: "antiemetics," "5-HT3 antagonist," "serotonin antagonist," "dolasetron," "granisetron," "ondansetron," tropisetron," "dexamethasone," "methylprednisone," "metoclopramide," "prochlorperazine," "aprepitant," "palonosetron," "L-754030," "L-758298," "substance P," "MK-869," and "receptors, neurokinin-1." Finally, these searches were combined serially with medical subject headings or text words corresponding to each of the major topical sections of the guideline, including, for example, "child" or "pediatric," "refractory" or "control," "radiotherapy" or "irradiation," and "bone marrow transplantation" or "high-dose chemotherapy."

Search results were limited to human studies and English-language articles. The Cochrane Library was searched with the phrase "antiemetic." Directed searches based on the bibliographies of primary articles were also performed. Finally, Update Committee members contributed articles from their personal collections. Specific Antiemetic Update Committee members were assigned to review the collected materials corresponding to the major sections of the guideline document.

The Update Committee's literature review focused on published randomized, controlled trials and systematic reviews and meta-analyses of published phase II and phase III randomized, controlled trials. The electronic literature searches identified a systematic review on aprepitant, a systematic review and meta-analysis on the role of neurokinin-1(NK₁) receptor antagonists in the prevention of emesis and nausea due to high-dose chemotherapy with cisplatin, a meta-analysis of randomized trials assessing the efficacy of dexamethasone in controlling chemotherapy-induced nausea and vomiting, and three systematic reviews and meta-analyses of 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonists. Prepublication copies of two additional systematic reviews were made available to the Update Committee by the Cancer Care Ontario Program in Evidence-Based Care and the Oregon Evidence-Based Practice Center, respectively.

The Update Committee also considered carefully the guidelines and consensus statements that emerged from the International Antiemetic Consensus Conference, hosted by the Multinational Association of Supportive Care in Cancer (MASCC; Perugia, Italy), in March 2004.

Not stated

Expert Consensus (Committee)

Not applicable

Review of Published Meta-Analyses
Systematic Review

The American Society of Clinical Oncology (ASCO) Antiemetic Guideline Update Committee's literature review focused on published randomized, controlled trials and systematic reviews and meta-analyses of published phase II and phase III randomized, controlled trials. The Update Committee also considered carefully the guidelines and consensus statements that emerged from the International Antiemetic Consensus Conference. Wherever possible, the Committee used the consensus statements and guidelines from the Multinational Association of Supportive Care in Cancer process to supplement other resources and to assist them in the preparation of this update.

Expert Consensus

The entire Update Committee met once to discuss strategy and to assign roles for the update. A writing committee collated different sections of the update prepared by the Update Committee members and edited the manuscript.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review

A final draft of the updated guideline was circulated to the full Update Committee for review and approval. The updated document was reviewed and approved by the American Society for Clinical Oncology (ASCO) Health Services Committee and by the ASCO Board of Directors.

Note from the National Guideline Clearinghouse and the American Society of Clinical Oncology: This guideline update presents the "current recommendation" for each of the topics considered in the original guideline: "no change" is indicated if a recommendation has not been revised after analysis of the literature search and Update Committee review.

Overview

The three-drug combination of a 5-hydroxytryptamine-3 (5-HT₃) serotonin receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy of high emetic risk. For persons receiving chemotherapy of high emetic risk, there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics. These agents should be reserved for patients intolerant of or refractory to 5-HT₃ serotonin receptor antagonists, neurokinin-1 receptor antagonists, and dexamethasone. The three-drug combination of a 5-HT₃ receptor serotonin antagonist, dexamethasone, and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide. For patients receiving other chemotherapy of moderate emetic risk, the Update Committee continues to recommend the two-drug combination of a 5-HT₃ receptor serotonin antagonist and dexamethasone. In all patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis. The Update Committee no longer recommends the combination of a 5-HT₃ serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk.

2006 Practice Recommendations

Emesis Caused by Intravenously Administered Antineoplastic Agents

Emesis, measured by counting the number of vomiting episodes after treatment, is the most important clinical trial end point for studies of antiemetic drugs. Studies have documented that the occurrence of complete response (no emetic episodes and no rescue medications administered after antineoplastic therapy) is a highly accurate and reliable measure. This outcome has also been demonstrated to correlate with the patients' perception of emesis. Nausea (the perception that emesis may occur) can be judged only by the patient. Although the incidence of nausea correlates with the incidence of vomiting, nausea generally occurs more frequently than vomiting. The Update Committee recommends the use of complete response for the guideline development process. Recent trials of aprepitant and palonosetron in patients receiving therapies of high or moderate emetic risk have recorded the incidence of vomiting, use of rescue therapy, and nausea for 5 days after antineoplastic treatment. The Update Committee recommends that the assessment of vomiting (no emesis and no rescue administered) and nausea for the 5 days after treatment be standard primary end points for antiemetic clinical trials in oncology.

Summary of Recommendations for Antiemetics in Oncology: Antiemetic Agents

Abbreviations: 5-HT₃, 5-hydroxytryptamine-3; NK₁, neurokinin 1.

Summary of Recommendations for Antiemetics in Oncology: Antiemetic Regimens

Abbreviations: 5-HT₃, 5-hydroxytryptamine-3; NK₁, neurokinin 1; AC, anthracycline and cyclophosphamide

Special Emetic Problems

Prevention of Anticipatory Emesis

Current recommendation. No change from original guideline. Use of the most active antiemetic regimens appropriate for the chemotherapy being administered to prevent acute or delayed emesis is suggested. Such regimens must be used with the initial chemotherapy, rather than after assessing the patient's emetic response with less effective treatment.

Treatment of Anticipatory Emesis

Current recommendation. No change from original guideline. If anticipatory emesis occurs, behavioral therapy with systematic desensitization is effective and is suggested.

Summary of Recommendations for Antiemetics in Oncology: Special Emetic Problems

Abbreviation: 5-HT₃, 5-hydroxytryptamine-3

Summary of Recommendations for Antiemetics in Oncology: Radiation-Induced Emesis

Abbreviation: 5-HT₃, 5-hydroxytryptamine-3

Drug Regimens for the Prevention of Chemotherapy-Induced Emesis by Emetic Risk Category (see Tables 8 and 9 in the original guideline document for doses, schedules, and routes of administration)

Abbreviation: 5-HT₃, 5-hydroxytryptamine-3

*For patients receiving a combination of an anthracycline and cyclophosphamide.

Drug Regimens for the Prevention of Emesis Selected by the Emetic Risk Category of the Radiation Administered

Abbreviation: 5-HT₃, 5-hydroxytryptamine-3

None provided

The type of evidence supporting the recommendations is not specifically stated.

Appropriate administration of antiemetics while considering patient's emetic risk categories and other characteristics.

Serotonin receptor antagonists (5-HT₃). These agents share similar adverse effect patterns, with mild headache, transient asymptomatic elevations in serum transaminase, and constipation reported.

Single-dose corticosteroids. Adverse effects of single dexamethasone doses are rare, although elevations of serum glucose levels, epigastric burning, and sleep disturbances occur.

Neurokinase 1 receptor antagonists: Concomitant administration of aprepitant with chemotherapy agents such as cyclophosphamide and docetaxel (which in part are cleared by CYP3A4) theoretically could decrease the clearance of these drugs, resulting in prolonged exposure and toxicity, or in the case of cyclophosphamide, decreased exposure to its active metabolite. There has been no evidence in patients with cancer receiving standard doses and schedules of aprepitant with chemotherapy that these theoretical issues have any clinical sequelae.

Metoclopramide and 5-HT3 Serotonin Receptor Antagonists. Several trials have reported efficacy for oral metoclopramide administered in combination with dexamethasone. This agent is generally well tolerated, with few acute dystonic reactions in adults. Akathisia (restlessness) may occur.

Subgroups Most Likely to be Harmed

Dopamine antagonists. Dopamine antagonists, especially when administered over several consecutive days, cause a high incidence of dystonic reactions and are not a good choice for general multiple-day use in the pediatric population.

• The American Society of Clinical Oncology (ASCO) considers adherence to these guidelines to be voluntary. The ultimate determination regarding their application is to be made by the physician in light of each patient's individual circumstances. In addition, these guidelines describe evaluations and administration of therapies in clinical practice; they cannot be assumed to apply to interventions performed in the context of clinical trials, given that such clinical studies are designed to test innovative management strategies in a disease for which better treatment is sorely needed. However, by reviewing and synthesizing the latest literature, this practice guideline serves to identify questions for further research and the settings in which investigational therapy should be considered.
• The risk of emesis with radiotherapy varies with the treatment administered. Only a minority of patients receives radiation therapy of high emetic risk, and, in that group of patients, the problem can be difficult to prevent or control. Controversy exists, caused by a lack of systematic study, concerning definitions of emetic risk groups. As with chemotherapy-induced emesis, it is the identification of these risk groups that indicates whether antiemetic therapy should be administered routinely on a preventative basis, or whether antiemetics should be reserved for treatment as needed by individual patients. The radiation oncology literature indicates that treatment field is one of the major determinants of emetic risk. More difficult to define, but also important considerations for risk, are the dose of radiotherapy administered per fraction and the pattern of fractionation. Using available data and clinical experience, the Update Committee reached consensus on definitions of four radiotherapy-induced emesis risk groups (see Table 10 in the original guideline document). This represents a modification from the 1999 guideline.

An implementation strategy was not provided.

Getting Better
Living with Illness

Effectiveness
Patient-centeredness

• Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006 Jun 20;24(18):1-16. [110 references]

Not applicable: The guideline was not adapted from another source.

1999 Sep (revised 2006 Jun 20)

American Society of Clinical Oncology - Medical Specialty Society

American Society of Clinical Oncology

2006 ASCO Antiemetic Guideline Update Expert Panel

Panel Members: Mark G. Kris, MD (Chair); Richard J. Gralla, MD; Maurice J. Chesney; Lawrence W. Chinnery; Rebecca Clark-Snow, RN, BSN, OCN; Petra Feyer, MD; Steven M. Grunberg, MD; Paul J. Hesketh, MD; Jim M. Koeller, MS; Gary R. Morrow, PhD, MS

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest.

*These authors have no disclosures to report.

No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about the American Society of Clinical Oncology's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

This is the current release of the guideline.

This guideline updates a previous version: American Society of Clinical Oncology. Recommendations for the use of antiemetics: Evidence-based, clinical practice guidelines. J Clin Oncol 1999 Sep;17(9):2971.

This summary was completed by ECRI on January 3, 2000. It was verified by the guideline developer on January 18, 2000. This NGC summary was updated by ECRI on July 25, 2006.

This summary is based on the original guideline, which is subject to the American Society of Clinical Oncology's copyright restrictions.