High-Dose Oral and Intravenous Metoclopramide in Doxorubicin/Cyclophosphamide-Induced Emesis A Randomized Double-Blind Study

Abstract

Emesis remains a major side effect of cancer chemotherapy. High-dose intravenous metoclopramide has proved to be effective antiemetic therapy for cisplatinum induced emesis. It has not been rigorously tested in nonplatinum chemotherapy. This double-blind, noncrossover, randomized trial compared high-dose oral and intravenous metoclopramide to standard oral prochlorperazine in emesis caused by doxorubicin [70 mg/m2 body surface area (BSA)] and cyclophosphamide (700 mg/m2 BSA). Prochlorperazine (10 mg/dose), oral metoclopramide, and intravenous metoclopramide (2 mg/kg/dose each) were given 30 min before chemotherapy and then every 4 h for 24 h. Ten patients were randomized to prochlorperazine therapy, 10 to oral metoclopramide, and 9 to i.v. metoclopramide. Median number of emeses for the first chemotherapy cycle was 3, 3, and 7 for prochlorperazine, oral, and i.v. metoclopramide, respectively. Statistical analysis showed no significant advantage of any regimen (p > 0.4). For patients who continued the antiemetic study, frequency of emesis increased with each successive cycle of chemotherapy. Six of 19 patients treated with metoclopramide developed dystonic reactions compared with zero of 10 on prochlorperazine. High plasma metoclopramide levels were achieved with both metoclopramide regimens and did not correlate with frequency of emesis. High-dose oral and i.v. metoclopramide in an every 4 h regimen did not show any advantage over standard antiemetic therapy for doxorubicin/cyclophosphamide-induced emesis and were associated with significant toxicity.