Chemotherapy-Induced Nausea and Vomiting

Byung Kim, M.D.
Bharti Rathore, M.D.

Basic Information

Definition

Chemotherapy-induced nausea and vomiting (CINV) refers to adverse emetic effects associated with the use of drugs used to treat cancer. There are five recognized subtypes:

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Acute-phase CINV: nausea and vomiting start within minutes to hours after receiving chemotherapy.
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Delayed-phase CINV: nausea and vomiting begin or return 24 hours or more after receiving chemotherapy.
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Breakthrough CINV: Occurring despite appropriate prophylactic treatment
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Anticipatory CINV: symptoms begin before receiving therapy as a conditioned response in patients who have developed significant nausea and vomiting during previous chemotherapy.
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Refractory CINV: Recurring in subsequent cycles of therapy, excluding anticipatory CINV

Synonyms

Drug-induced nausea and vomiting
Chemotherapy-induced emesis
CINV

ICD-10CM CODES
R11.2	Nausea with vomiting, unspecified
R11.0	Nausea
R11.10	Vomiting, unspecified
Z51.11	Encounter for antineoplastic chemotherapy

Epidemiology & Demographics

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The patient’s risk for development of nausea and vomiting is most strongly dependent on the emetogenicity of the chemotherapy agent(s) being used.
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Emetogenicity is classified into four categories: highly emetic (>90%), moderately emetic (>30%–90%), low emetic (10%–30%), and minimally emetic (0%–10%).
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With certain chemotherapy regimens, CINV will occur in the majority of patients. However, patients’ tolerance may vary, and symptoms may occur in as low as 10% of patients.
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Symptoms may be dose dependent (the higher the dose, the greater the risk for symptoms).
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CINV is more likely to affect female and younger patients.
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Patients expecting CINV before receiving therapy (anticipatory emesis) are at greater risk of experiencing symptoms.
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Patients with a history of alcohol consumption are at lower risk.
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Patients with a history of motion sickness are at greater risk.

Incidence

The highest incidence of CINV is before or during the first cycle of chemotherapy.

Genetics

Some rapid metabolizers of certain 5-HT3 receptor antagonists and polymorphisms in the 5-HT3 receptor confer greater risk for CINV.

Risk Factors

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Previous history of CINV.
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History of motion sickness or vestibular dysfunction.
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Higher levels of anxiety.
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History of alcohol use decreases risk.

Physical Findings & Clinical Presentation

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Symptoms may include anxiety and lightheadedness.
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The most common physical findings are increased pulse rate and abnormal blood pressure (elevated if the person is highly anxious, reduced if the patient is dehydrated).
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Symptoms such as diarrhea, fever, headache, and abdominal pain may suggest an alternative diagnosis; physical examination findings such as increased blood pressure, abdominal tenderness, or focal neurologic deficits may suggest symptoms caused by cancer progression or other acute illness such as infection.

Pathophysiology

CINV is likely the result of chemotherapy acting in two places: directly in the gastrointestinal tract and in the vomiting center of the brain. In both areas, nausea and vomiting are mediated by the actions of certain neurotransmitters, with serotonin, dopamine, and neurokinin-1 being the most important.

Diagnosis

Differential Diagnosis

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The two main considerations are progression of cancer and infection
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Intestinal/gastric: obstruction or partial obstruction of the digestive tract from tumor
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Neurologic: metastases to the brain causing vomiting; metastatic infiltration of nerves affecting the digestive tract
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Infectious: acute bacterial, viral, or parasitic infections of the digestive tract causing symptoms (can be associated with diarrhea or pain)
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Renal: dehydration leading to acute kidney injury and failure, causing worsening of nausea and vomiting

Workup

No workup is indicated if patient’s symptoms and onset of nausea and vomiting fit the usual presentation for CINV. If other symptoms or unexpected physical examination findings are present, then other causes need to be ruled out. A combination of blood work and imaging may be helpful.

Laboratory Tests

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If the onset of symptoms is not typical for CINV, then blood tests such as a CBC, liver function tests, electrolytes, and kidney function tests may be indicated.
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Stool studies looking for infections from viruses, bacteria, or parasites may be ordered if diarrhea is also present.

Imaging Studies

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Abdominal radiographs may be ordered to look for obstruction of the digestive tract but will not provide any information about tumor progression.
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Abdominal CT scan may provide more detailed information about local cancer progression/invasion in the proximity of the digestive tract and whether obstruction of the digestive tract is present.
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CNS imaging with CT scan or magnetic resonance imaging (MRI) of the brain may provide information about possible metastases.

Treatment

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Choice and duration of antiemetic use are dependent on the chemotherapy regimen used.
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For chemotherapy agents with high emetogenic potential, the use of multidrug antiemetic regimens has proven to be highly effective in symptom prevention.
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The most common treatment combination includes a serotonin-receptor antagonist (ondansetron, granisetron, dolasetron, or palonosetron), a corticosteroid (methylprednisolone or dexamethasone), and a neurokinin-1 receptor antagonist (aprepitant, rolapitant, or fosaprepitant).
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A fixed-dose combination of oral palonosetron and netupitant (NK-1 receptor antagonist) is now available.
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Many other adjunct drugs are available, such as olanzapine, prochlorperazine, metoclopramide, haloperidol, and marinol; comparatively, they are less effective and have greater potential for adverse effects.
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Benzodiazepines (usually lorazepam) may help in patients with significant anxiety levels that lead to anticipatory CINV.
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Patients with uncontrolled symptoms may require hospitalization for supportive care including intravenous medications and fluids.

Nonpharmacologic Therapy

For those patients with a significant anxiety component to their CINV, cognitive behavioral therapy may help.

Disposition

Although CINV is one of the most feared complications of cancer therapy, its treatment has been revolutionized in the last 20 years, with most patients achieving adequate symptom control.

Pearls & Considerations

Comments

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Aggressive symptom control in the acute phase of CINV is the key initial therapeutic approach. Prevention of the acute phase has led to much improved control of the delayed phase and has greatly decreased the incidence of anticipatory CINV.
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Prevention of symptoms is much easier to achieve than controlling or treating active symptoms.

Ferri – Chemotherapy-Induced Nausea and Vomiting