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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
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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
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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
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Antiemetic Principles1,2,3,4,5,6,7
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...