Comparison of Metoclopramide and Metoclopramide Plus Dexamethasone for Complete Protection from Cisplatinum-Induced Emesis

Abstract

Metoclopramide was compared to a metoclopramide plus dexamethasone combination in patients receiving high-dose cisplatinum. Metoclopramide 2 mg/kg intravenously was given every 2 hours for 4 doses during two consecutive chemotherapy cycles. A randomized double-blind crossover was used with placebo or dexamethasone 20 mg given intravenously before the first metoclopramide dose. Thirty-six patients completed both study arms. There was no difference in mean vomiting episodes (1.92 for metoclopramide versus 1.33 for the combination, p = 0.20). However complete protection (no vomiting episodes) was achieved in 56% receiving the combination but only 36% receiving metoclopramide alone (p less than 0.08). No significant difference in toxicity or patient preference was noted. Late nausea or vomiting lasting 2 to 7 days appeared in 26% of cycles and was associated with but not completely explained by a greater number of acute vomiting episodes. Combination antiemetic therapy can achieve a higher incidence of complete protection from cisplatinum-induced vomiting. However, late nausea and vomiting may require modification of present regimens.

Control of Acute Cisplatin-lnduced Emesis over Repeat Courses of Chemotherapy

“…As with metoclopramidc [4][5][6][7][8], the efficacy of ondansetron can be en hanced by dexamethasone [14,15]. This might suggest that a combination of ondansetron plus dexamethasone could replace metoclopramide plus dexamethasone and diphenhydramine or lorazépam as standard first-line therapy in the prevention of acute cisplatin-induced eme sis.…”

“…This may be administered as 1-2 mg/kg i.v. every 2 h for 3-6 doses combined with méthylprednisolone or dexamethasone [4][5][6][7][8], However, the optimal antiemetic regimen with metoclopramide had not been established. A study was therefore conducted in 1986-1988 which compared a standard high-dose metoclopramide regimen plus methylprednisolone (treatment A) with a shorter but higher dose regimen of metoclopramide in association with dexamethasone and diphenhydramine (treatment B) in 367 patients receiving cisplatin doses > 50 mg/m2 as part of their chemotherapy regimen (table 1) [9].…”

Ondansetron plus Dexamethasone Compared to the ‘Standard’ Metoclopramide Combination

“…The addition of dexamethasone to ondansetron and metoclopramide enhances their efficacy [4][5][6][7][8], Furthermore, the addition of diphenhydramine or lorazépam to regimens containing metoclopramide in creases efficacy even further, and can be used to counter the side effects of metoclopramide [9,10]. Prior to the introduction of the 5-HTi receptor antagonists, combina tions such as metoclopramide plus dexamethasone and diphenhydramine or lorazépam were generally regarded as the most effective anti-emetic treatments for the con trol of emesis induced by high-dose cisplatin chemothera py.…”

The control of acute cisplatin-induced emesis – a comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone

“…Gralla et al (1981) were the first to use high doses of metoclopramide for the prevention of emesis and demonstrated improved anti-emetic efficacy of this agent used in this way, especially in patients receiving high-dose cisplatin containing regimens where up to 40% of patients could be controlled with metoclopramide alone. Combination with corticosteroids (Grunberg et al, 1986) further improved control and the addition of a benzodiazepine such as lorazepam was shown to improve the subjective effectiveness of the combinations (Kris et al, 1985a) and up to 60% of patients could now be completely controlled (Kris et al, 1987). However, the use of these regimens is associated with a number of side effects such as extrapyramidal reactions (Kris et al, 1983) and sedation.…”