Chapter 39: Prophylaxis and Treatment of Chemotherapy-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 is effective and has been used with some success

Antiemetic Principles^{1,2,3,4,5,6,7}

• 5-HT₃ receptor antagonists demonstrate comparable efficacy at equivalent doses. In general, they can be used interchangeably based on convenience, availability, and cost. Evidence from clinical trials suggests palonosetron may be more effective than other 5-HT₃-receptor antagonists in preventing delayed CINV. Clinical practice guidelines from the Multinational Association of Supportive Care in Cancer (2010), and the American Society of Clinical Oncology (2011 update) recommend palonosetron as the preferred 5-HT₃ receptor antagonist in prophylaxis for chemotherapy of moderate emetic potential when aprepitant is not included in the regimen.^2,4,6 The National Comprehensive Cancer Network antiemesis guideline (version 1.2012) recommends palonosetron as the preferred 5-HT₃ receptor antagonist in prophylaxis for both high and moderate emetic risk categories³

• The lowest established proven dose of each 5-HT₃ receptor antagonist should be used

• Single-dose prophylactic regimens of 5-HT₃ receptor antagonists and corticosteroids for acute phase CINV prophylaxis are effective and preferred

• At biologically equivalent doses, oral antiemetic regimens are equivalent to intravenous antiemetic regimens

• All patients receiving chemotherapy should have antiemetics available on a PRN basis for breakthrough nausea and vomiting. Rescue agents should be selected to complement, not duplicate the prophylactic regimen (ie, select drugs from a different pharmacologic class)

• For CINV prophylaxis where there is a high emetic potential (emetic incidence of >90%), an antiemetic regimen that includes a 5-HT₃ receptor antagonist, a corticosteroid, and aprepitant (NK₁...