DOSE-RESPONSE RELATIONSHIPS OF THE OBJECTIVE AND SUBJECTIVE ANTIEMETIC EFFECTS AND OF DIFFERENT SIDE-EFFECTS OF METOCLOPRAMIDE AGAINST CISPLATIN INDUCED EMESIS

  • 1 January 1986
    • journal article
    • research article
    • Vol. 36-2  (12) , 1845-1849
Abstract
The graded and quantal responses of metoclopramide (MCL, Paspertin) were studied in patients (17-71 years) treated with cisplatin in combination with other cytostatics. The lowest dose of MCL was 0.125 mg/kg b.w./h i.v. over 2 h as loading infusion, then 0.0625 mg/kg/h over 24 h as the maintenance infusion, the total dose being 1.75 mg/kg per treatment cycle (n = 25). At the same schedule three different higher doses of MCL were run with total doses of 3.5 (n = 44), 7.0 (n = 120), and 14.0 (n = 161) mg/kg per cycle of cisplatin. The mean number of emetic episodes in historical control patients without MCL (n = 41) at the four different doses of cisplatin was 4.2 episodes at 25 mg/m2 of cisplatin 6.9 episodes at 60 mg/m2, 14.9 at 90, and 21.6 episodes at 120 mg/m2 of cisplatin. The quantitative dose-response curves of the four doses of the emetic agonist cisplatin were shifted to the right by increasing doses of MCL. The following doses of cisplatin for .gtoreq. 95% antiemetic protection (i.e. only 0-2 emetic episodes as clinically sufficient protection) were obtained (at the respective mg/kg of MCL given in brackets): 13 (at 1.75 MCL), 25 (at 3.5 MCL), 42 (at 7 MCL), and 80 (at 14 MCL) mg/m2 of cisplatin, respectively. The MCL dose in order to provide .gtoreq. 95% of the patients against every mg/m2 of cisplatin was about 0.15 (range 0.13-0.18) mg/kg MCL per cycle (i.e. 6.5 mg/m2 of cisplatin are antagonized by 1 mg/kg of MCL). Dose-response curves of the subjective self-estimated scores of nausea of the patients were also obtained. These ran nearly parallel and were shifted to the right depending on the dose of MCL. The risk of severe extrapyramidal side effects (EPS), i.e. akathisia and/or acute dystonia, was not dependent on the dose of MCL: The mean number of EPS per cycle at the four different doses of MCL was 0.23-0.41-0.45-0.36. From the results its concluded that the emetogenic potency of the agonist cisplatin can be antagonized quantitatively by the respective doses of the antagonist given above. In addition, there will be an improving benefit/risk ratio with increasing doses of metoclopramide.