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    Drug Information Question

     

    Drug Information Question


    A breast cancer patient twice experienced severe continued nausea and vomiting after receiving her chemotherapy that continued for up to 3 or 4 days following treatment. She comes in to the clinic daily for 4 days following chemotherapy to receive antiemetic therapy consisting of intravenous (IV) 5-HT3 receptor antagonist therapy with dexamethasone and IV fluids. Is this antiemetic therapy selection appropriate?

    Delayed nausea and vomiting can be a seriously distressing problem for patients. It may cause them to become very discouraged and, in some cases, may affect willingness to continue therapy. This can result in serious health consequences for these patients.

    Initial studies showed that 5-HT3 receptor antagonists were not consistently effective in the treatment of delayed chemotherapy-induced nausea and vomiting. Urinary excretion of the serotonin metabolite, 5-HIAA, peaks at 6 hours after cisplatin chemotherapy administration and returns to pretreatment levels by 24 hours1; therefore, it seems reasonable to conclude that delayed nausea and vomiting is not associated with serotonin release and that other mechanisms must be involved.

    Ondansetron alone has been shown to be no more effective than placebo in the management of delayed nausea and vomiting.2-4 Cyclophosphamide and cisplatin-based therapies are most often associated with delayed emesis. Based on results from further studies, however, an increased effectiveness has been noted when dexamethasone is administered along with a 5-HT3 receptor antagonist following cyclophosphamide, doxorubicin, or carboplatin therapy, and with the administration of dexamethasone along with metoclopramide or a 5-HT3 receptor antagonist after cisplatin therapy in adults.3 In a double-blind, controlled trial comparing placebo, dexamethasone, and the combination of dexamethasone and metoclopramide in cisplatin-treated patients, metoclopramide combined with dexamethasone was effective,4 particularly when given 2 to 3 days after cisplatin therapy.

    Oral therapy, however, should be administered in this case, if possible, because of cost and patient convenience issues. The preferable treatment is the combination of a step-down dosing regimen of dexamethasone (8 mg bid for 2 days, then 4 mg bid for 2 additional days) with oral metoclopramide or prochlorperazine, or a 5-HT3 receptor antagonist when the latter 2 agents fail.

     






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