Dose-response relationships of the objective and subjective antiemetic effects and of different side effects of metoclopramide against cisplatin induced emesis.

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 greater than or equal to 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 greater than or equal to 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).(ABSTRACT TRUNCATED AT 250 WORDS)