Nausea and Vomiting During Cancer Treatment

Welcome to this video on cancer-related nausea and vomiting. Nausea and vomiting are two of the most common side-effects associated with cancer and cancer treatments.

Nausea, that feeling of having to vomit, is subjective and can result in a feeling of revulsion toward food, and the inability to eat and can influence compliance with treatment.

Vomiting, on the other hand, is objective and can result in physiological changes and complications that further impair health and may become life-threatening.

Causes of Nausea and Vomiting

Nausea and vomiting occur when stimuli send input to the vomiting center of the central nervous system that is located in the medulla oblongata of the brain and in the spinal cord. These stimuli originate in 4 different areas:

• First, the chemoreceptor trigger zone, which is also located in the medulla oblongata and is able to detect blood-borne emetic agents (such as chemotherapeutic agents) and send this information to the vomiting center
• Second, the gastrointestinal viscera
• Third, the vestibular system in the temporal lobe AND
• Fourth, the cortical mechanisms related to sensory input and emotions, such as a smell or anxiety that act as a trigger

Once triggered, the vomiting center induces the vomiting reflex.

With cancer, the cause of nausea and vomiting can vary but may include any of the following:

• The type of tumor: Cancer of the GI tract, lung cancer, brain tumor, and ovarian cancer increase risk.
• Extent of the tumor: The larger the tumor, the greater the risk of nausea and vomiting.
• Comorbid conditions, such as renal or hepatic failure, bowel obstruction, cerebellar metastasis, hypothyroidism, central nervous system disorders (including increased intracranial pressure), and diabetic ketoacidosis. Those with a history of motion sickness or Meniere’s disease are at increased risk.
• Infections, such as sepsis, meningitis, hepatitis, COVID-19, and viral gastroenteritis.
• Gender and age: Females are more prone to developing nausea and vomiting than males AND people under age 50 are more likely to develop nausea and vomiting than older people.
• Stress and anxiety
• Uncontrolled pain
• Opioids
• Chemotherapy AND
• Radiation therapy

Chemotherapy is especially implicated in the development of nausea and vomiting, and chemotherapeutic agents are assigned emetogenic ratings depending on their risk of causing nausea and vomiting ranging from minimally emetogenic to highly emetogenic.

• With minimally emetogenic agents, the risk is less than 10% of developing nausea and vomiting. Examples include chlorambucil, hydroxyurea, methotrexate, erlotinib bleomycin, busulfan, vinblastine, rituximab, and vincristine.
• With low emetogenic agents, risk is 10 to 30%: Examples include fludarabine, sunitinib, dasatinib, paclitaxel, everolimus, docetaxel, fluorouracil, gemcitabine, and mitomycin.
• With moderately emetogenic agents, risk is 30 to 90%: Examples include temozolomide, vinorelbine, ceritinib, carboplatin, cytarabine, doxorubicin, and oxaliplatin AND
• With highly emetogenic agents, risk is greater than 90%: Examples include hexamethylmelamine, procarbazine, cisplatin, anthracycline/cyclophosphamide combination, mechlorethamine, carmustine, and streptozocin.

There are different patterns of nausea and vomiting associated with chemotherapy, including:

• Acute nausea and vomiting occur with abrupt onset within a few minutes up to several hours after treatment and usually don’t last for more than 24 hours.
• Delayed nausea and vomiting, on the other hand, occur about 24 hours after treatment and peak at 48 to 72 hours but can persist in some individuals for up to a week.
• Breakthrough nausea and vomiting occur if medications and treatments aimed at preventing or treating nausea and vomiting become ineffective after a few days or if preventive measures fail.
• Refractory nausea and vomiting tend to occur after multiple treatments to control nausea and vomiting have failed. Refractory nausea and vomiting do not respond to the usual treatments.
• Anticipatory nausea and vomiting occur before treatment when an individual anticipates becoming nauseated. This can be triggered by anything the person associates with the chemotherapy, such as a smell, sound, or sight.
• Anticipatory nausea and vomiting typically occur after the individual has experienced a previous episode of nausea and vomiting, so this is a conditioned response. Risk factors include young age, female gender, history of motion sickness, and a history of pregnancy-related nausea and vomiting. Those who experience dizziness, increased perspiration, or the feeling of being hot after chemotherapy also have increased risk of developing anticipatory nausea and vomiting.

Nausea and vomiting are graded according to severity:

• Grade 1 is 1 or 2 episodes separated by 5 minutes in a 24-hour period.
• Grade 2 is 3 to 5 episodes separated by 5 minutes in a 24-hour period.
• Grade 3 is 6 or more episodes separated by 5 minutes in a 24-hour period, resulting in the need for tube feeding, total parenteral nutrition, or hospitalization.
• Grade 4 is when life-threatening complications occur AND
• Grade 5 results in death.

Interventions

Both nonpharmacological and pharmacological interventions are used to control nausea and vomiting.

Nonpharmacological approaches to control nausea and vomiting include:

• Self-hypnosis, which typically includes relaxation and imagery.
• Guided imagery or visualization to overcome negative conditioned stimuli.
• Biofeedback, which helps to control physiological responses.
• Progressive muscle relaxation to reduce anxiety.
• Cognitive distraction to focus attention away from nausea and vomiting.
• Music therapy to reduce anxiety AND
• Acupuncture and acupressure, which are both effective in reducing nausea and vomiting.

People can easily be taught to use acupressure by applying pressure to the pressure point P-6 or Neiguan point, which is found 3 finger-widths proximal to the hand on the inner wrist.

To carry out acupressure, position the fingers to find the site and then place the thumb below the index finger and apply firm but not painful pressure in a circular motion for 2 to 3 minutes. Follow the same procedure on the opposite wrist.

Drugs that are commonly used to treat nausea and vomiting include:

• NK-1 receptor antagonists, such as rolapitant, aprepitant, and fosaprepitant
• Corticosteroids, such as oral or intravenous dexamethasone
• D5-HT3 receptor antagonists, such as dolasetron, granisetron, ondansetron, and palonosetron
• Olanzapine
• Netupitant
• Metoclopramide
• Cannabinoids, such as dronabinol and nabilone
• Anticholinergics, such as belladonna alkaloid and scopolamine transdermal patch, AND
• Benzodiazepines, such as alprazolam and lorazepam

Medications are usually provided before chemotherapy and continued after the treatment is finished. If nausea and vomiting is delayed, then the treatment may continue for a number of days.

Adequate prevention and management of nausea and vomiting depend on the type of nausea and vomiting, the cause, and the emetogenic rating of the chemotherapeutic agent, often resulting in the need for multiple interventions. The same medications may be used for different types of nausea and vomiting but in different combinations or doses.

For example, anticipatory nausea and vomiting may be treated with self-hypnosis and distraction as well as a benzodiazepine.

For acute or delayed nausea and vomiting with highly emetogenic chemotherapeutic agents, relaxation, acupressure, and a combination of drugs may be utilized, including an NK-1 receptor antagonist, such as rolapitant; a corticosteroid, such as dexamethasone; and a 5-HT3 receptor antagonist, such as granisetron.

For breakthrough nausea and vomiting, an additional drug that is different from those previously administered is tried along with nonpharmacological interventions, such as acupressure and relaxation exercises.

Radiation treatments cause nausea and vomiting in 50% to 80% of those receiving the treatments. The greatest risk is for those receiving full-body radiation, as 90% experience nausea and vomiting.
Between 30% and 90% of those receiving upper abdominal or craniospinal radiation also develop nausea and vomiting. Radiation to the brain, head, neck, breasts, extremities, and pelvis incur a lower rate ranging from 10% to 30% of nausea and vomiting. The pathophysiology isn’t totally clear but appears to involve increased levels of serotonin.

The most effective treatment for radiation-induced nausea and vomiting, according to studies, is a 5-HT3 receptor antagonist, such as granisetron or ondansetron along with dexamethasone.

Typically, for high-risk radiation therapy, the 5-HT3 receptor antagonist and dexamethasone are administered on the days of therapy before treatment and the day after if no treatment is scheduled that day.

When people are receiving chemotherapy and radiation therapy concurrently, then antiemetic protocols for chemotherapy are generally used.

Adverse Effects

Nausea and vomiting can result in a number of adverse effects, such as:

• General discomfort, which can include cold sweats, increased salivation, tachycardia, and abdominal muscle contractions
• Electrolyte imbalances, such as hypokalemia (which can lead to cardiac arrhythmias and even death), and hypochloremic metabolic acidosis
• Dehydration
• Malnutrition
• Weight loss
• Esophageal rupture or tear with bleeding OR
• Aspiration of emesis, leading to aspiration pneumonia

Healthcare providers should establish an early plan to prevent and manage nausea and vomiting for those with cancer. Preventing nausea and vomiting is especially important for people’s wellbeing, to reduce incidence of anticipatory nausea and vomiting and to increase compliance with treatment.

That’s all for this review! Thanks for watching, and happy studying!