Principles, Updates in Chemotherapy-Induced Nausea, Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of
the most distressing and feared adverse effects (AEs) that patients
can experience while receiving chemotherapy.¹ In addition to adversely impacting patients’ quality of life, CINV can lead to treatment delays, dose reductions, and potentially compromised treatment outcomes.^2,3

Antiemesis guidelines help clinicians design optimal antiemetic prevention and treatment regimens to help patients maintain treatment adherence and improve their quality of life.³

Types of CINV

CINV is classified into 5 types: acute, delayed, breakthrough, refractory, and anticipatory.³ Acute CINV and delayed CINV correlate with time parameters, as acute CINV occurs within 24 hours of the initial administration of chemotherapy, and delayed CINV occurs after 24 hours and may persist for as long as 7 days after antineoplastic therapy administration.²

However, not all CINV is classified by time of occurrence, as anticipatory CINV is understood as a conditioned response to a prior experience of CINV,³ while breakthrough CINV is nausea and/ or vomiting that occurs despite the use of appropriate prophylaxis. Additionally, refractory CINV is defined as nausea and/or vomiting that continues to occur in subsequent chemotherapy cycles.

Pathophysiology of CINV

CINV is a complex process that involves communication between several neurotransmitters and their receptors, which can be triggered by chemotherapy administration.¹ Known as the main mediator of acute emesis, serotonin (5-HT3) is transmitted via a peripheral pathway mechanism that originates in the gastrointestinal tract.

The neurotransmitter called substance P, which binds to the neurokinin-1 (NK-1) receptors in the central nervous system, is thought to be predominantly involved in delayed CINV via the central pathway. Dopamine, histamine, and acetylcholine are also involved and may serve as additional targets for antiemetic therapies.²

Antiemetic Strategies and Principles

The goal of antiemesis therapy is to prevent CINV by using an appropri-
ately designed antiemetic prophylaxis regimen.^4,5 When clinicians are deciding on an antiemetic regimen, the emetogenic potential of chemotherapy is the most important treatment-related factor for prevention of CINV.^3,4

In addition, there are patient-specific risk factors that may affect the development of CINV and should be considered when selecting antiemetic agents. Patient risk factors include age, gender, prior CINV, anxiety, alcohol intake history, and history of motion sickness. Equally important, type of CINV, comorbidities and contraindications, patient adherence, and cost should also be considered, further complicating antiemetic regimen selection.^6,7 To address these challenges during the selection process, there are several updated guidelines available to help clinicians design individualized antiemetic prophylaxis and treatment.

Pharmacologic Therapy

To maximize antiemetic control, agents of different mechanisms of action are combined. Corticosteroids, 5-HT3 receptor antagonists (5-HT3 RA), and NK-1 receptor antagonists (NK-1 RA) are the main pharmaco- logic classes of medications that serve as the backbone of antiemetic reigmens.³

Development of 5-HT3 RAs—such as ondansetron, granisetron, and dolasetron—has revolutionized CINV management by preventing up to 80% of acute nausea.⁵ Furthermore, the addition of a second-generation 5-HT3 RA known as palonosetron has been shown to also provide improved delayed antiemetic prophylaxis by action of a longer half-life.

NK-1 RAs such as aprepitant, fosaprepitant, neupitant, and rolapitant have enhanced our ability to prevent delayed CINV. Olanzapine, a second- generation antipsychotic, is an effective addition to both prevention and treatment of CINV owing to its mechanism of action, which targets serotonin, dopamine, adrenergic, and histamine receptors.⁵

Additionally, benzodiazepines’ place in therapy is mostly in the prevention of anticipatory CINV, but also in breakthrough and refractory settings.³ Dopamine antagonists, anticholinergics, antihistamines, and cannabinoids are also useful in managing breakthrough or refractory CINV.^3,4

Antiemesis Guideline Updates

The current guidelines on antiemesis that are used in clinical practice come from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the Multinational Association of Supportive Care in Cancer (MASCC).

The most recent update was published by NCCN in March 2021, with one key update in the option of a lower, 5-mg dose of olanzapine for CINV prophylaxis with high or moderate emetic risk of chemotherapy regimens.⁶ This was a change from a previously recommended dose of 10 mg, as new data have found that a lower dose is efficacious. The guidelines now recommend a 5- to 10-mg range, but the lower dose may help alleviate some of the AEs of olanzapine, such as sedation in older patients.

In the update, several clinical pearls were added, including recommendation for morning administration of dexamethasone to minimize insomnia, and olanzapine evening administration to mitigate sedation. Also recommended is a short-term only administration of metoclopramide to minimize the risk of tardive dyskinesia. MASCC antiemetic guidelines are currently under revision.

The 2020 edition of ASCO’s antiemetics guideline update also included the option of a lower, 5-mg dose of olanzapine.⁷ Based on newer data, ASCO recommends the addition of olanzapine to the antiemetic prophylaxis regimen in the setting of hematopoietic stem cell transplantation.

Additionally, ASCO addressed in the guideline a common question asked in clinical practice regarding the omission of dexamethasone, explaining that no clinical evidence exists to support omission of dexamethasone from antiemetic regimens when checkpoint inhibitors are used in combination with chemotherapy.

Prevention of CINV is the most important goal of antiemetic therapy; it ensures patients can complete their chemotherapy regimens while maintaining their quality of life.5 For this reason, staying up to date on the current guidelines and clinical trial data is critical for oncology care providers so that they can design the best possible CINV prevention and treatment strategies.

Alina Varabyeva, PharmD, is a leukemia clinical pharmacist specialist at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Allison Monahan, PharmD, BCPS, is a clinical pharmacist generalist at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

REFERENCES

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