Guidelines on Radiation- and Chemotherapy-Induced Nausea and Vomiting

Updated: May 31, 2018
  • 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, 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]

Next:

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)

Antiemetic agents

Neurokinin 1 receptor antagonist (NK1 RA):

  • Aprepitant (APR) PO/IV
  • Fosaprepitant (FOS)
  • Netupitant/palonosetron (fixed NK1 RA and selective 5-hydroxytryptamine receptor antagonist [5-HT3 RA] combination)

 5-HT3 RA:

  • Dolasetron
  • Granisetron PO/IV/transdermal
  • Ondansetron
  • Palonosetron
  • Dexamethasone (DEX) PO/IV
  • Olanzapine PO - Off-label use for prevention of chemotherapy associated nausea or vomiting in combination with 5-HT3 antagonist and DEX [5]

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): NK1 RA + 5-HT3 RA + DEX or

Olanzapine + palonosetron +DEX or

NK1 RA + 5-HT3 RA + DEX + olanzapine

Days 2-4: Varies according to day 1 regimen

Day 1 (before chemotherapy): NK1 RA + 5-HT3 RA + DEX + olanzapine

Days 2-4: continue olanzapine on days 2-4

Add DEX on days 2-4 for high-emetic risk (non-AC)

Acute: 5-HT3 RA + NK1 RA + DEX

Delayed (non-AC): DEX

Delayed (non-AC) if APR 125 mg for acute: metoclopramide (MCP) + DEX or APR+ DEX

Delayed (AC): None

Delayed (AC) if APR 125 mg for acute: DEX or APR

Moderate

Day 1 (before chemotherapy): 5-HT3 RA + DEX or  Olanzapine + palonosetron +DEX orNK1 RA + 5-HT3 RA + DEX

Days 2-3:  Varies according to day 1 regimen

Treated with 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 (carboplatin regimens): 5-HT3 RA + DEX+ NK1 RA

Acute (excluding carboplatin-based): 5-HT3 RA + DEX

Delayed (carboplatin regimens): None

Delayed (carboplatin regimens) if APR 125 mg for acute: APR

Low

Start before chemotherapy: DEX or  MCP PO/IV or  prochlorperazine or  oral 5-HT3 RA

Acute: 5-HT3 RA or DEX

Acute: DEX or 5-HT3 RA ordopamine receptor antagonist (DOP)

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 (eg, dronabinol, nabilone)
  • Haloperidol
  • Metoclopramide
  • Scopolamine transdermal
  • Phenothiazine (eg, promethazine, prochlorperazine)
  • 5-HT3 RA
  • DEX

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)
  • NK1 RA
  • Olanzapine
  • 5-HT3 RA
  • Sustained-release granisetron
  • Transdermal granisetron
  • Triple drug regimen: NK1 RA + 5-HT3 RA + DEX

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
  • Lorazepam [Ativan], diphenhydramine [Benadryl], and haloperidol [Haldol] gel (ABH gel)
  • Ayurvedic 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.

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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: : 5-HT3 RA + DEX
  • Moderate-risk RT: 5-HT3 RA; short course of DEX is optional
  • Low-risk RT to cranium: DEX as either prophylaxis or rescue
  • Low-risk RT to head and neck, thorax region, pelvis: DEX, DOP, or 5-HT3 RA as either prophylaxis or rescue
  • Minimal-risk RT: Rescue with DEX, DOP, 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.

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