Managing Chemotherapy- and Radiation Therapy-Induced Nausea and Vomiting

Prevention and Management

Assessing patients’ risks of treatment-related nausea and vomiting involves assessment of patients, their treatment histories, and the emetogenicity of their planned treatments’ specific drugs and doses.³

Important advances in the development of pharmacologic antiemetic regimens for the prevention and management of CINV and RINV should improve patients’ quality of life and reduce the incidence of emesis-associated side-effects and complications.⁴ Given the number of available treatment options, ongoing patient evaluation and monitoring are appropriate to find the approach that works best for each individual patient.³ However, standard antiemetic regimens for preventing CINV now involve combination therapies such as a 5-HT₃ receptor antagonist and/or NK1 receptor antagonist with dexamethasone.⁴

Until the 1980s, prevention and management of treatment-related nausea and vomiting involved dopamine receptor antagonist therapies. Since then, antiemetic treatment strategies and agents have proliferated.³

In October 2017, the American Society of Clinical Oncology (ASCO) updated its clinical practice guideline for antiemetics, reflecting an expert panel’s systematic review of 41 studies published in the medical research literature between 2009 and June 2016.⁴ The updated ASCO guideline presents new evidence-based information about the role of NK1 receptor antagonists, dexamethasone, and olanzapine.⁴ Key updated guideline recommendations will be reviewed below.

Proposed nonpharmacologic interventions for acute and delayed CINV and RINV include dietary changes, hypnosis, guided imagery, acupuncture and acupressure, and relaxation techniques.¹ However, these have been less studied than pharmacologic interventions.

5-HT₃ Receptor Antagonists

Serotonin receptor (5-HT₃) antagonists have replaced dopamine receptor antagonists as a cornerstone of CINV prevention and management.³ They were first introduced in the early 1990s.³ Ondansetron, granisetron, dolasetron, and palonosetron (the most recently approved agent [2003]) each affect serotonin binding in the vagal nerve terminals or the medulla oblingata’s chemoreceptor trigger zone.³ 5-HT₃ receptor antagonists disrupt the peripheral vagal nerves’ and brainstem chemoreceptor trigger zone’s signaling, which is involved in triggering nausea and vomiting.³ 5-HT₃ adverse events are usually mild and can include headache and constipation, transient elevations in liver function enzymes and prolongation of cardiac QTc interval.^1,3

For RINV prevention, ondansetron, dolasetron, or tropisetron can be administered once or on consecutive days for up to 5 to 7 days, according to the NCI.¹

Neurokinin-1 (NK₁) receptor antagonists

NK₁ receptor antagonists like aprepitant block substance P activity and thereby disrupt emetic stimuli pathways. Because it inhibits CYP-3A4 cytochrome, combination NK₁ plus dexamethasone antiemetic regimens should employ reduced-dose dexamethasone, which is a CYP-3A4 substrate.³

Fosaprepitant (150 mg single dose) is an intravenously administered aprepitant prodrug approved for pre-chemotherapy prophylaxis against CINV.³

No clinical studies have assessed NK₁ receptor antagonists for prevention of RINV.¹

Corticosteroids

Corticosteroids like the glucocorticoid dexamethasone are frequently included in CINV-prophylactic antiemetic regimens. They appear to offer some protection against low emetic risk chemotherapy CINV alone but are frequently combined off-label with 5-HT₃ receptor antagonists for patients receiving high-emetic-risk chemotherapy.³ However, the U.S. Food and Drug Administration (FDA) has not approved corticosteroids for CINV prophylaxis or treatment. Their molecular mechanism of action is unclear.³ Side-effects can be a problem and include insomnia, stomach discomfort, and hyperglycemia.³

Dexamethasone has been shown to improve RINV symptoms for patients undergoing upper-abdominal irradiation.⁶ Corticosteroids can also be combined with the 5-HT₃ receptor antagonist ondansetron for patients receiving upper-abdominal radiotherapy.¹