Alizapride is a methoxy-2-benzamide derivative three times more potent than its parent compound,
metoclopramide, as an antagonist of
apomorphine-induced
emesis in dogs. The
antiemetic activity of
alizapride plus
dexamethasone (DXM) was compared with that of placebo plus DXM in a randomized, double-blind, crossover study in
cancer patients receiving
cisplatin (DDP).
Alizapride, given at the maximally tolerated dose of 4 mg/kg x 5, or placebo was given in a sequence determined by randomization during two successive, identical courses of antitumor
chemotherapy. The
antiemetic treatment was given 30 min before and 1.5, 3.5, 5.5, and 7.5 h after starting. DXM, in a dose of 12 mg, was given IV with the first administration of
alizapride or placebo. A total of 39 patients completed the two courses of
chemotherapy. The severity of gastrointestinal symptoms was influenced by previous treatment but not by the treatment sequence. Although our overall results suggest that
alizapride does not add to the activity of DXM against DDP-induced amesis, a statistically significant difference favoring
alizapride plus DXM was found among patients with the lowest gastrointestinal tolerance to DDP: women, patients under 50 years of age, and patients pretreated with
chemotherapy including DDP and non-DDP agents. Side effects consisted of
orthostatic hypotension, which was symptomatic in two patients, and a single occurrence of severe extrapyramidal syndrome. We conclude that
alizapride is more active than placebo when combined with DXM for DDP-induced
emesis in patients at high risk of severe
nausea and
vomiting. The severity of the side effects in this study indicates that a
dose reduction of
alizapride might be appropriate for further studies.