Guidelines on Radiation- and Chemotherapy-Induced Nausea and Vomiting

Updated: Sep 05, 2017
  • Author: Winston W Tan, MD, FACP; more...
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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, chemotherapy, targeted treatment, or immunotherapy. The treatment team should review the potential emetogenic potential of each treatment regimen, based on published information. In addition, 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. it is also important to review all medications that the patient is taking to check for possible drug interaction.

 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]


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] as are the NCCN risk ratings, although the NCCN list of agents is more extensive. [1] Single-agent cisplatin and the combination of an anthracycline and cyclophosphamide (AC) are rated at high risk by all three organizations. [1, 2, 3] ASCO and NCCN recommend that in patients receiving combination chemotherapy, antiemetic treatment should be determined according to the agent posing the greatest degree of emetic risk. [1, 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
  • Consider using lorazepam as an adjuvant to the antiemetic regimen to decrease anxiety in patients at risk for anticipatory emesis
  • Consider using an H2 blocker or a proton pump inhibitor to prevent dyspepsia
  • Consider other potential causes of emesis in cancer patients (eg, bowel obstruction)

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 Day 1 (before chemotherapy): Neurokinin 1 receptor antagonist (NK1 RA) (aprepitant [APR], fosaprepitant [FOS], rolapitant) + Selective 5-hydroxytryptamine receptor antagonist (5-HT3 RA) (palonosetron, granisetron, ondansetron, dolasetron) + dexamethasone (DEX) or  Netupitant/palonosetron (NEPA) + DEX or

Olanzapine + palonosetron +DEX or APR or FOS + 5-HT3 RA + DEX + olanzapine

Days 2-4: Varies according to day 1 regimen

NK1 RA + 5-HT3 RA + DEX + olanzapine; continue olanzapine on days 2-4 Acute:  5-HT3 RA + NK1 RA + DEX

Delayed: DEX + NK1 RA (cisplatin) or NK1 RA (anthracycline + cyclophosphamide)

Moderate Day 1 (before chemotherapy): 5-HT3 RA + DEX  or  NK1 RA + 5-HT3 RA + DEX or   NEPA + DEX or Olanzapine + palonosetron + DEX

Days 2-3:  Varies according to day 1 regimen

Patients receiving carboplatin area under the curve (AUC) ≥ 4 mg/mL/min: NK1 RA + 5-HT3 RA + DEX

Other moderate-risk regimens: 5-HT3 RA + DEX on day 1

Delayed: DEX on days 2-3

Acute: 5-HT3 RA + DEX

Delayed: DEX on days 2-3

Low Start before chemotherapy: DEX or  metoclopramide or  prochlorperazine or  5-HT3 RA (dolasetron, granisetron, ondansetron) Acute: 5-HT3 RA or  DEX

Delayed: No routine prophylaxis

Acute: DEX or   5-HT3 RA  or dopamine receptor antagonist (eg, metoclopramide)

Delayed: No routine prophylaxis

Minimal No routine prophylaxis No routine prophylaxis No routine prophylaxis

Breakthrough treatment

NCCN guidelines advise that the general principle of breakthrough treatment is to add one agent from a different class than in the patient's current regimen. Any of the following may be selected [1] :

  • Olanzapine
  • Lorazepam
  • Cannabinoid - Dronabinol, nabilone
  • Haloperidol
  • Metoclopramide
  • Scopolamine transdermal
  • Prochlorperazine
  • Promethazine
  • 5-HT3 RA
  • Dexamethasone

Oncology Nursing Society Recommendations

The ONS practice recommendations for CINV in adults include the following [4] :

  • Cannabis/cannabinoids
  • Dexamethasone-sparing regimen
  • Netupitant-palonosetron combination (NEPA)
  • Neurokinin 1 (NK1) receptor antagonists
  • Olanzapine
  • Selective 5-hydroxytryptamine (5-HT3) receptor antagonists
  • Sustained-release agranisetron
  • Transdermal granisetron
  • Triple drug regimen: Dexamethasone, 5‐HT3 receptor antagonist, and NK1 receptor antagonist

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

  • Adherence to CINV guidelines
  • Benzodiazepine for anticipatory CINV
  • Gabapentin
  • Hypnosis for anticipatory CINV
  • Managing patient expectations
  • Olanzapine for breakthrough CINV
  • Oral palonosetron
  • Progestins
  • Progressive muscle relaxation and guided imagery
  • Single-agent dexamethasone

The ONS considered the benefits balanced with harm for virtual reality, which has been evaluated for providing distraction and reducing anxiety as means of CINV prevention.

The effectiveness of the following treatments was not considered established:

  • Acupressure
  • Acupuncture/electroacupuncture
  • Acustimulation
  • Aromatherapy
  • ABH gel (lorazepam [Ativan], diphenhydramine [Benadryl], and haloperidol [Haldol] gel)
  • Aryuvedic drugs
  • Carbamazepine
  • Chamomilla recutita
  • Electronic antinausea device (ELANI)
  • Exercise
  • Ginger
  • Grape Juice
  • Guided imagery/imagery alone
  • Haloperidol
  • Herbal medicine
  • Hologram bracelet
  • Institutional initiatives
  • Massage/aromatherapy massage
  • Metoclopramide (prophylactic)
  • Metopimazine
  • Mirtazapine
  • Nevasic audio
  • Ondansetron as rescue medication
  • Prochlorperazine for breakthrough CINV
  • Progressive muscle relaxation (PMR)
  • Psychoeducation/Psychoeducational interventions
  • Thalidomide
  • Therapeutic touch
  • Yoga

The ONS also found cocculine unlikely to be effective and that expert opinion supports the adjunctive use of lorazepam for CINV prevention.


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-hydroxytryptamine receptor antagonist (5-HT3 RA) plus dexamethasone
  • Moderate-risk RT: 5-HT3 RA; short course of dexamethasone is optional
  • Low-risk RT to cranium: Dexamethasone as either prophylaxis or rescue
  • Low-risk RT to head and neck, thorax region, pelvis: Dexamethasone, dopamine receptor antagonist, or 5-HT3 RA as either prophylaxis or rescue
  • Minimal-risk RT: Rescue with dexamethasone, dopamine receptor antagonist, or 5-HT3 RA

National Comprehensive Cancer Network and American Society of Clinical Oncology Recommendations

For patients receiving radiation therapy (RT) to the upper abdomen/localized sites or total body irradiation, the NCCN recommends pretreatment for each day of RT with either of the following:

  • Granisetron with or without dexamethasone
  • Ondansetron with or without dexamethasone

For breakthrough emesis, the NCCN recommendations are the same as for CINV breakthrough treatment. 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]

in the setting of combined modality treatment with chemo-radiation it is important to tailor the management individually and depending on the emetogenic potential of the drug.