Guidelines on Radiation- and Chemotherapy-Induced Nausea and Vomiting

Updated: Jun 28, 2016
  • Author: Winston W Tan, MD, FACP; more...
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Overview

Overview

Nausea and vomiting (N/V) is a common complication of cancer treatment and a common cause of anxiety and distress in patients, in some cases even prior to their first chemotherapy session. It is important for oncologist/hematologists and their teams to recognize the significance of N/V and to create a strategy to address it. Prevention of N/V is ideal. Once N/V occurs, every effort should be made to eliminate it, or at least to minimize it.

Emesis can result from radiation therapy or chemotherapy. The treatment team should review the potential emetogenic potential of each chemotherapy and radiation therapy regimen, based on published information. In addition, however, each patient should be individually assessed for this risk before the initiation of treatment and should be re-assessed regularly throughout treatment. The ability of an agent to cause immediate and delayed N/V should be reviewed, so that the administration of antiemetogenic agents can be timed appropriately.

 The following organizations have released guidelines for the management of emesis resulting from treatment of cancer:

  • National Comprehensive Cancer Network (NCCN)
  • Multinational Association for Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO)
  • American Society of Clinical Oncology (ASCO)
  • Oncology Nursing Society (ONS)

The NCCN, MASCC/ESMO, and ASCO guidelines include management recommendations for both chemotherapy-induced nausea and vomiting (CINV) and radiation-induced nausea and vomiting (RINV). [1, 2, 3] The ONS recommendations are limited to CINV. [4]

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Chemotherapy-Induced Nausea and Vomiting

Treatment recommendations are based on four types of chemotherapy-induced nausea and vomiting (CINV), as follows:

  • Acute: Onset of emesis within a few minutes to several hours after chemotherapy is administered and usually peaking in the first 4-6 hours
  • Delayed: Onset of emesis more than 24 hours after chemotherapy is administered
  • Anticipatory: Onset of emesis prior to chemotherapy administration as a conditioned response in patients who have experienced emesis during a previous cycle of chemotherapy
  • Breakthrough/refractory: Emesis despite prophylactic/breakthrough medications

All the guidelines use the following system to classify chemotherapy agents into the following risk groups:

  • High emetic risk:  ≥90% or more of patients experience emesis
  • Moderate emetic risk: 30% to 90% of patients experience emesis
  • Low emetic risk: 10% to 30% of patients experience emesis
  • Minimal emetic risk: <10% of patients experience emesis

The MASCC/ESMO and ASCO risk ratings for individual chemotherapy agents are similar, [2, 3] as are the NCCN risk ratings, although the NCCN list of agents is more extensive. [1] The combination of an anthracycline and cyclophosphamide (AC) is rated at high risk by all three organizations. [1, 2, 3] ASCO recommends that in patients receiving combination chemotherapy, antiemetic treatment should be determined according to the agent posing the greatest degree of emetic risk. [3]

NCCN guidelines state that the best management of acute or delayed CINV is prevention; patients should be protected before receiving chemotherapy and for the full period of risk (up to 4 days) afterward. General recommendations for prevention are as follows [1] :

  • Prevention of acute emesis should start before chemotherapy and continue for the first 24 hours
  • Choice of antiemetic agent should be based on the emetic risk of the chemotherapy regimen
  • Prevention of delayed emesis is a continuation of prophylactic treatment for 2 to 4 days following completion of chemotherapy
  • Because breakthrough/refractory emesis is difficult to reverse, prevention using routine around-the-clock administration of antiemetics is preferred over as-needed (PRN) dosing
  • Prevention is also key to the management of anticipatory emesis
  • Relaxation/systematic desensitization, hypnosis with guided imagery, and music therapy are behavioral interventions that may be considered for anticipatory emesis; acupuncture/acupressure are additional options
  • The addition of lorazepam and alprazolam as an adjuvant to the antiemetic regimen is recommended to decrease anxiety in patients at risk for anticipatory emesis

Recommended antiemetic agents by emetic-risk categories are shown in the table below.

Table. Antiemetic Treatment Recommendations (Open Table in a new window)

Risk Level National Comprehensive Cancer Network Recommendations American Society of Clinical Oncology Recommendations Multinational Association for Supportive Care in Cancer/European Society for Medical Oncology Recommendations
High Selective 5-hydroxytryptamine (5-HT3) antagonist (palonosetron preferred) + dexamethasone (DEX) + aprepitant (APR) or  fosaprepitant (FOS) ± lorazepam or



Olanzapine + palonosetron +DEX ± lorazepam ± H2 blocker or proton pump inhibitor



Acute: Selective 5-HT3 antagonist + DEX + APR



Delayed: DEX + APR



Acute: Selective 5-HT3 antagonist + DEX + APR or FOS



Delayed: DEX + APR or DEX only if FOS used on day 1



Anthracycline + cyclophosphamide (AC)   Acute: Selective 5-HT3 antagonist + DEX + APR



Delayed: APR



Acute: Selective 5-HT3 antagonist + DEX + APR or FOS



Delayed: APR or none if FOS used on day 1



Moderate Day 1: Selective 5-HT3 antagonist + DEX ± APR or FOS or olanzapine + palonosetron + DEX ± lorazepam ± H2 blocker or proton pump inhibitor



Day 2: Selective 5-HT3 antagonist  unless palonosetron used on day one  or



DEX  or



APR or FOS ± DEX ± lorazepam ± H2 blocker or proton pump inhibitor or



Olanzapine ± lorazepam ± H2 blocker or proton pump inhibitor



Acute: Selective 5-HT3 antagonist (palonosetron preferred) + DEX



Delayed: Selective 5-HT3 antagonist or DEX



Acute: Palonosetron + DEX



Delayed: DEX



Low DEX or  selective 5-HT3 antagonist or  dopamine receptor antagonist (DRA) or prochlorperazine ± lorazepam ± H2 blocker or proton pump inhibitor Acute: DEX



Delayed: No routine prophylaxis



Acute: DEX or  selective 5-HT3 antagonist  or DRA



Delayed: No routine prophylaxis



Minimal No routine prophylaxis No routine prophylaxis No routine prophylaxis

NEPA (Akynzeo), a fixed-dose combination of netupitant (a neurokinin 1 [NK1] receptor antagonist with a long half-life of 90 minutes) and palonosetron, has demonstrated efficacy in patients receiving highly and moderately emetogenic chemotherapy. [5, 6] In a focused guideline update, ASCO added the recommendation of offering all patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) the combination of an NK1 antagonist, a 5-HT3 antagonist, and dexamethasone; NEPA plus dexamethasone is an additional treatment option. [7]

Oncology Nursing Society Recommendations

The ONS recommendations for treatment include the following [4] :

  • 5-Hydroxytryptamine (5‐HT3) receptor agonists (palonosetron, granisetron, ondansetron, dolasetron, tropisetron)
  • Neurokinin 1 (NK1) receptor antagonist (aprepitant)
  • Combination drug regimen: Dexamethasone, 5‐HT3 receptor antagonist, and NK1 receptor antagonist
  • Cannabinoids

In addition, the following treatments were considered by ONS likely to be effective:

  • Gabapentin
  • Hypnosis (for anticipatory CINV)
  • Netupitant-palonosetron combination (NEPA)
  • Olanzapine (for breakthrough CINV)
  • Progestins
  • Progressive muscle relaxation and guided imagery
  • Single-agent dexamethasone

The effectiveness of the following treatments was not considered established:

  • ABH gel (lorazepam [Ativan], diphenhydramine [Benadryl], and haloperidol [Haldol] gel)
  • Acupressure
  • Acupuncture
  • Acustimulation
  • Carbamazepine
  • Electroacupuncture
  • Exercise
  • Ginger
  • Grape Juice
  • Guided imagery/imagery alone
  • Haloperidol
  • Herbal medicine
  • Massage/aromatherapy massage
  • Metoclopramide (prophylactic)
  • Mirtazapine
  • Olanzapine (prophylactic)
  • Ondansetron (as rescue medication)
  • Prochlorperazine (for breakthrough CINV)
  • Progressive muscle relaxation (PMR) alone
  • Psychoeducation/Psychoeducational interventions
  • Thalidomide
  • Yoga

The ONS also found coculine unlikely to be effective and metopimazine was not recommended.

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Next:

Radiation-Induced Nausea and Vomiting

The ASCO and MASCC/ESMO guidelines categorize radiation therapy sites in terms of their risk for radiation-induced nausea and vomiting (RINV) as follows [2, 3] :

  • High risk: Total body irradiation and total nodal irradiation
  • Moderate risk: Upper abdomen, half body irradiation, upper body irradiation
  • Low risk: Cranium, craniospinal, head and neck, lower thorax region, pelvis
  • Minimal risk: Extremities, breast

Multinational Association for Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) recommendations for patients receiving radiation therapy (RT) are keyed to risk level, and include the following [2] :

  • High-risk RT: Selective 5-HT3 antagonist plus dexamethasone
  • Moderate-risk RT: Selective 5-HT3 antagonist; short course of dexamethasone is optional
  • Low-risk RT: Selective 5-HT3 antagonist as either prophylaxis or rescue
  • Minimal-risk RT: Dexamethasone or selective 5-HT3 antagonist

National Comprehensive Cancer Network and American Society of Clinical Oncology Recommendations

The NCCN recommendation for treatment of RINV is a selective 5-HT3 receptor antagonist with or without dexamethasone. [1] The ASCO recommendations for RINV include the following [3] :

  • Patients receiving high-risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for at least 24 hours after completion of radiotherapy; patients should also receive a 5-day course of dexamethasone during fractions 1 to 5.
  • Patients receiving moderate-risk radiation should receive a 5-HT3 receptor antagonist before each fraction for the entire course of radiotherapy; patients may be offered a short course of dexamethasone during fractions 1 to 5
  • Patients receiving low-risk radiation therapy should receive a 5-HT3 receptor antagonist alone as either prophylaxis or rescue; for patients who experience radiation-induced nausea and vomiting (RINV) while receiving rescue therapy only, prophylactic treatment should continue until radiotherapy is complete
  • Patients receiving minimal-risk radiation therapy should receive rescue therapy with either a dopamine receptor antagonist or a 5-HT3 receptor antagonist; antiemetic prophylaxis should continue throughout radiation treatment if a patient experiences RINV while receiving rescue therapy

For management of emesis during concurrent radiation and chemotherapy, the NCCN and ASCO guidelines agree that the optimal approach is to give antiemetic prophylaxis according to the emetogenicity of the chemotherapy. [1, 3]

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