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
| Recommendations |
Category |
Current Recommendations |
| 5-HT3 serotonin receptor antagonists |
Agent equivalence |
At equivalent doses for the prevention of acute emesis, 5-HT3 serotonin, serotonin receptor antagonists have equivalent safety and efficacy and can be used interchangeably. |
| Drug dosage |
No change from the original guideline. Use only established doses. |
| Drug schedule |
No change from the original guideline. Single doses are preferred. |
| Route of administration |
No change from the original guideline. At biologically equivalent doses, oral formulations are equally effective and safe as intravenous antiemetics. |
| Corticosteroids |
Agent equivalence and route of administration |
No change from the original guideline. At equivalent doses, corticosteroids have equivalent safety and efficacy and can be used interchangeably. Dexamethasone is preferred because of its extensive clinical study and wide availability. |
| Drug dose and schedule |
Single doses of dexamethasone are recommended. |
| NK1 receptor antagonist (aprepitant) |
Drug dose and schedule |
Only the established dose and schedule of aprepitant should be used. |
Abbreviations: 5-HT3, 5-hydroxytryptamine-3; NK1, neurokinin 1.
Summary of Recommendations for Antiemetics in Oncology: Antiemetic Regimens
| Recommendation Category |
Current Recommendations |
| Specific emetic risk categories |
High (>90%) emetic risk. The three-drug combination of a 5-HT3 serotonin receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy. In all patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended. The Update Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone on days 2 and 3. |
| Moderate (>30% to 90%) emetic risk. The three-drug combination of a 5-HT3 receptor serotonin antagonist, dexamethasone, and aprepitant is recommended for patients receiving AC. For patients receiving chemotherapy of moderate emetic risk other than AC, the Update Committee recommends the two-drug combination of a 5-HT3 receptor serotonin antagonist and dexamethasone. In patients receiving AC, aprepitant as a single agent is recommended on days 2 and 3. For all other chemotherapies of moderate emetic risk, single-agent dexamethasone or a 5-HT3 serotonin receptor antagonist is suggested for the prevention of emesis on days 2 and 3. |
| Low (10% to 30%) emetic risk. Dexamethasone 8 mg is suggested. No routine preventive use of antiemetics for delayed emesis is suggested. |
| Minimal (<10%) emetic risk. No change from the original guideline. No antiemetic should be administered routinely before or after chemotherapy. |
| Combination chemotherapy. No change from the original guideline. Patients should be administered antiemetics appropriate for the chemotherapeutic agent of greatest emetic risk. |
| Multiple consecutive days of chemotherapy. No change from the original guideline. It is suggested that antiemetics appropriate for the risk class of the chemotherapy, as outlined above, be administered for each day of the chemotherapy and for 2 days after, if appropriate. |
| Antiemetic agents: lower therapeutic index. 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, NK1 receptor antagonists, and dexamethasone. |
| Antiemetic agents: adjunctive drugs. Lorazepam and diphenhydramine are useful adjuncts to antiemetic drugs, but are not recommended as single agents. |
| Antiemetic agents: combinations of antiemetics. It is recommended that 5-HT3 serotonin receptor antagonists be administered with dexamethasone and aprepitant in patients receiving chemotherapy of high emetic risk and in patients receiving AC. A 5-HT3 serotonin receptor antagonist combined with dexamethasone should be used in patients receiving agents of moderate emetic risk other than AC. |
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
| Recommendation Category |
Current Recommendations |
| Emesis in pediatric oncology patients |
The combination of a 5-HT3 antagonist plus a corticosteroid is suggested before chemotherapy in children receiving chemotherapy of high or moderate emetic risk. Due to variation of pharmacokinetic parameters in children, higher weight-based doses of 5-HT3 antagonists than those used in adults may be required for antiemetic protection. |
| High-dose chemotherapy |
No change from original guideline. A 5-HT3 serotonin receptor antagonist antiemetic combined with dexamethesone is suggested. Aprepitant should be considered although evidence to support its use specifically in these patients is lacking. |
| Vomiting and nausea despite recommended prophylaxis |
No change from original guideline. The Update Committee suggests that clinicians (1) conduct a careful re-evaluation of emetic risk, disease status, concurrent illnesses, and medications; (2) ascertain that the best regimen is being administered for the emetic risk; (3) consider adding lorazepam or alprazolam to the regimen; and (4) consider substituting a high-dose intravenous metoclopramide for the 5-HT3 antagonist or adding a dopamine antagonist to the regimen. |
Abbreviation: 5-HT3, 5-hydroxytryptamine-3
Summary of Recommendations for Antiemetics in Oncology: Radiation-Induced Emesis
| Recommendation Category |
Current Recommendations |
| High risk: total-body irradiation |
No change from original guideline. The Update Committee suggests giving a 5-HT3 serotonin receptor antagonist with or without a corticosteroid before each fraction and for at least 24 hours after. |
| Moderate emetic risk: upper abdomen (intermediate risk) hemibody irradiation, upper abdomen, abdominal-pelvic, mantle, craniospinal irradiation, and cranial radiosurgery |
The Update Committee recommends a 5-HT3 serotonin receptor antagonist before each fraction. |
| Low emetic risk: lower thorax, cranium (radiosurgery), and craniospinal |
No change from original guideline. The Update Committee recommends a 5-HT3 serotonin receptor antagonist before each fraction. |
| Minimal emetic risk: radiation of breast, head and neck, cranium, and extremities |
No change from original guideline. The Update Committee suggests that treatment be administered on an as-needed basis only. Dopamine or 5-HT3 serotonin receptor antagonists are advised. Antiemetics should be continued prophylactically for each remaining radiation treatment day. |
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)
| Emetic Risk Category (incidence of emesis without antiemetics) |
Antiemetic Regimens and Schedules |
| High (>90%) |
5-HT3 serotonin receptor antagonist: day 1 |
| Dexamethasone: days 1, 2, 3 |
| Aprepitant: days 1, 2, 3 |
| Moderate (30% to 90%) |
5-HT3 serotonin receptor antagonist: day 1 |
| Dexamethasone: day 1 |
| (Aprepitant: days 1, 2, 3)* |
| Low (10% to 30%) |
Dexamethasone: day 1 |
| Minimal (<10%) |
Prescribe as needed (see text in the original guideline document for details of agent selection) |
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
| Radiation Emetic Risk |
Irradiated Area |
Recommendations |
| High (> 90%) |
Total body |
Prophylaxis with 5-HT3 serotonin receptor antagonist +/- dexamethasone with each fraction and 24 hours after |
| Moderate (60% to 90%) |
Upper abdomen |
Prophylaxis with 5-HT3 serotonin receptor antagonist |
| Low (30% to 60%) |
Lower thorax, pelvis, cranium (radiosurgery), and craniospinal |
Prophylaxis or rescue with 5-HT3 serotonin receptor antagonist |
| Minimal (< 30%) |
Head and neck, extremities, cranium, breast |
Rescue with dopamine receptor antagonist or 5-HT3 serotonin receptor antagonist |
Abbreviation: 5-HT3, 5-hydroxytryptamine-3
