Chapter 42: Prophylaxis and Treatment of Chemotherapy- and Radiation-Induced Nausea and Vomiting

Chemotherapy-Induced Nausea and Vomiting (CINV)

Neurotransmitters and their receptor targets implicated in CINV

• Serotonin and the serotonin subtype 3 (5-HT₃) receptor

• Dopamine and the dopamine subtype 2 (D₂) receptor

• Substance P and the neurokinin subtype 1 (NK₁) receptor

• Histamine, acetylcholine, opioids, and their respective receptors

Two Phases of CINV

Acute phase

• Occurs during the first 24 hours after exposure to emetogenic chemotherapy and is mediated by release of serotonin from enterochromaffin cells within GI tract

• Actual time of onset varies depending on the chemotherapeutic agent

Delayed phase

• Substance P and the NK₁ receptor may be more important than serotonin in delayed CINV

• Delayed CINV was initially described with cisplatin

• Delayed CINV has also been described with other chemotherapeutic agents, including carboplatin, cyclophosphamide, and the anthracyclines

• Although the onset of delayed emesis was initially defined as that which occurs 24 hours postchemotherapy, more recent evidence suggests that referable symptoms may occur as early as 16 hours after cisplatin

• The incidence of delayed vomiting after cisplatin is greatest during the 24-hour period from 48 to 72 hours after treatment, and, thereafter, declines progressively

Anticipatory Nausea and Vomiting

• Development is associated with poor emetic control during prior administration of chemotherapy

• Prevention is the best approach

• Pharmacologic interventions are usually not successful, but behavioral methods with systemic desensitization are effective and have been used with some success

Radiation-induced Nausea and Vomiting (RINV)

• The emetic risk associated with radiation therapy is primarily based on the site of radiation. Patients receiving total-body, upper-abdomen, and craniospinal irradiation incur the greatest risk for nausea and vomiting. Risk categories based on site are provided in Table 42–9

Antiemetic Principles^1–5

• 5-HT₃ receptor antagonists demonstrate comparable efficacy at equivalent doses. In general, they can be used interchangeably based on convenience, availability, and cost. Clinical trials and subsequent meta-analysis studies have demonstrated that palonosetron is more effective than other 5-HT₃ receptor antagonists in preventing CINV, particularly in the delayed phase. However, these trials did not include NK₁ receptor antagonists within the trial design and many did not consistently include corticosteroids such as dexamethasone. Clinical practice guidelines from the Multinational Association of Supportive Care in Cancer (2016) suggest that palonosetron is preferred in moderately emetogenic chemotherapy when dexamethasone is not included and in AC (anthracycline plus cyclophosphamide) chemotherapy when an NK1 receptor antagonist is not included.^3,4 The National Comprehensive Cancer Network (NCCN) antiemesis guideline (version 2.2020) recommends palonosetron as the preferred 5-HT₃ receptor antagonist in prophylaxis for high and moderate emetic risk categories when an NK₁ receptor antagonist is not included in the regimen.² The NCCN antiemesis guidelines also recommend subcutaneous granisetron extended-release injection as a preferred 5-HT₃ receptor antagonist when used with dexamethasone without an NK₁ receptor antagonist. This recommendation is based on a phase ...