Summary
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.
Similar content being viewed by others
References
Aapro MS, Alberts DS (1981) High-dose dexamethasone for prevention of cisplatin-induced vomiting. Cancer Chemother Pharmacol 7:11
Aapro MS, Plezzia PM, Alberts DS, Graham V, Jones SE, Surwit EA, Moon TE (1984) Double-blind cross over study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide. J Clin Oncol 2:466
Cassileth PA, Lusk EJ, Torri S, Dinubile N, Gerson SL (1983) Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. Arch Intern Med 143:1347
Frytak S, Moertel CG (1981) Management of nausea and vomiting in the cancer patient. J Am Med Assoc 245:393
Gralla RJ, Squillante AE, Steele N, Kelsen DP, Young CW (1980) Phase I: intravenous trial of the antiemetic metoclopramide in patients receiving cis-platinum (DDP). Proc Am Soc Clin Oncol 21:350
Gralla RJ, Itri LM, Pisko SE, Squillante AE, Kelsen DP, Braun DW, Bordin LA, Braun TJ, Young CW (1981) Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 305:906
Herman TS, Einhorn LH, Jones SE, Nagy C, Chester AB, Dean JC, Furnas B, Williams SD, Leigh SA, Dorr RT, Moon TE (1979) Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. N Engl J Med 300:1295
Kris MG, Tyson LB, Gralla RJ, Clark RA, Allen JA, Reilly LK (1983) Extrapyramidal reactions with high-dose metoclopramide. N Engl J Med 309:433
Laville C, Margarit J (1982) Etude pharmacodynamique de l'alizapride. Sem Hop 58:323
Morrow FA (1984) The assessment of nausea and vomiting. Cancer 53:2267
Morrow GA, Morrell C (1982) Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. N Engl J Med 307:1476
Nicaise C, Rozencweig M, Ortmans M, Frisque C, Bleiberg H (1983) Etude en phase I de l'alizapride chez des patients cancéreux traités au cisplatine. Sem Hop 59:2161
Panettiere FG (1981) Cis-platinum (CAPC) toxicity. An analysis based on 3 swog studies. Proc Am Assoc Cancer Res 22:157
Pater JL, Willan AR (1984) Methodologic issues in trials of antiemetics. J Clin Oncol 5:484
Pommatau E (1982) Etude en double insu croisé alizaprideplacebo sur la prévention des nausées et des vomissements induits par la chimiothérapie antimitotique. Sem Hop 58:363
Poster DS, Penta JS, Brunno S, MacDonald JS (1981) 9-tetrahydrocannabinol in clinical oncology. J Am Med Assoc 245:2047
Rozencweig M, Von Hoff DD, Slavik M, Muggia FM (1977) cis-Diamminedichloroplatinum(II): a new anticancer drug. Ann Intern Med 86:803
Siegel LJ, Longo DL (1981) The control of chemotherapy-induced emesis. Ann Intern Med 95:352
Siegel S (1956) Non parametric statistics for behavioral sciencies, International Student edn. McGrant-Hill Kogakusha Ltd, Tokyo
Viala JJ, Girard D, Codier JF (1982) Etude en double insu d'un nouvel anti-émétique, l'alizapride, dans les nausées et vomissements de la chimiothérapie anti-cancéreuse. Sem Hop 58:371
Author information
Authors and Affiliations
Additional information
Gastroenterology Unit
Chemotherapy Unit
This work was supported in part by the Fonds National de la Recherchge Scientifique Médicale (FRSM 3.4521.83), Belgium; the National Cancer Institute (NCI/NIH) (N01/CM 53840), Bethesda, Maryland; and l'Association Sportive contre le Cancer, Belgium
Rights and permissions
About this article
Cite this article
Bleiberg, H., Gerard, B., Dalesio, O. et al. Activity of a new antiemetic agent: alizapride. Cancer Chemother. Pharmacol. 22, 316–320 (1988). https://doi.org/10.1007/BF00254238
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00254238