Ondansetron plus Metopimazine Compared with Ondansetron Alone in Patients Receiving Moderately Emetogenic Chemotherapy

Jorn Herrstedt*, Tine Sigsgaard, Marianne Boesgaard, Tina P. Jensen, Per Dombernowsky

*Corresponding author af dette arbejde

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    Abstrakt

    Background and Methods: The serotonin (5-hydroxytryptamine3) antagonists have improved the treatment of acute chemotherapy-induced nausea and vomiting, but their ability to prevent delayed nausea and vomiting seems less pronounced. The results of a preliminary open trial suggested that the addition of a selective dopamine D2 antagonist could improve the antiemetic efficacy of the serotonin antagonists. In a randomized, double-blind, crossover trial, we compared oral treatment with ondansetron (8 mg twice a day) and the dopamine D2 antagonist metopimazine (30 mg four times a day) with treatment with ondansetron alone for three days in 30 patients who had vomited during the previous cycle of chemotherapy. All the patients received moderately emetogenic chemotherapy. Results: Combination treatment with ondansetron and metopimazine significantly reduced the incidence of acute (P = 0.006) and delayed (P = 0.02) nausea and acute (P = 0.02) and delayed (P = 0.006) vomiting, as compared with treatment with ondansetron alone. Patients had significantly fewer days of nausea (P = 0.03) and vomiting (P = 0.003) if they received combination therapy. Sixty-seven percent of the patients preferred ondansetron and metopimazine, and 33 percent favored ondansetron alone (P = 0.10). Adverse reactions were mild with both regimens. With the exception of constipation, which was reported more frequently with combination therapy (P = 0.03), there were no significant differences in adverse reactions. Conclusions: Ondansetron plus metopimazine is a highly effective and safe antiemetic regimen that is markedly superior to treatment with ondansetron alone in patients receiving moderately emetogenic chemotherapy., Chemotherapy-induced emesis is thought to be mediated by receptors located in the chemoreceptor trigger zone of the area postrema and in the gastrointestinal tract. Until recently, dopamine D2 receptors were considered the most important, but the identification of serotonin (5-hydroxytryptamine3) receptors in these two areas1,2 and the finding that the dopamine D2 antagonist metoclopramide, when given in high doses, is also a serotonin antagonist1 and probably owes its antiemetic effect to the blockade of this receptor, have necessitated a reexamination of the mechanism. Today, more selective and potent serotonin antagonists have been developed, and the…

    OriginalsprogEngelsk
    Sider (fra-til)1076-1080
    Antal sider5
    TidsskriftNew England Journal of Medicine
    Vol/bind328
    Udgave nummer15
    DOI
    StatusUdgivet - 15 apr. 1993

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