bemesetron and Nausea

This pilot randomized study compared MDL 72,222, a highly selective 5-HT3 receptor antagonist, with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. MDL 72,222 was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion. The HDM was composed of diphenhydramine 50 mg i.v., metoclopramide 2 mg/kg i.v., and lorazepam 0.04 mg/kg i.v. administered 30 minutes before chemotherapy and 2, 4, 6, and 8 hours after chemotherapy. Patients were randomized to either MDL 72,222 (n = 12) or the HDM (n = 12) and were matched for age, weight, Karnofsky performance status, and chemotherapy. More patients in the MDL 72,222 group had received prior cisplatin. The MDL 72,222 group and the HDM group received a mean cisplatin dose of 66 mg/m2 and 62 mg/m2, respectively. Patients were observed for retching and/or emesis for 24 hours and completed a visual analog scale (VAS) for nausea. Six MDL 72,222 and five HDM patients had no vomiting. One MDL 72,222 and two HDM patients had one episode of emesis within 24 hours of chemotherapy. The median number of emetic episodes in the first 24 hours was 0.5 for MDL 72,222 and 1.0 for HDM patients. HDM patients were frequently asleep and were not awakened for evaluation of nausea with the VAS; 58% (70 of 120) of the HDM (mean score: 19.1 mm) and 14% (17 of 119) of the MDL 72,222 (mean score: 17.1) patients could not have VAS scores obtained (X2 = 50.74, p < 0.001). MDL 72,222 had similar efficacy with less sedation, and further trials are warranted.

Topics: Adult; Aged; Antiemetics; Cisplatin; Diphenhydramine; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Lorazepam; Metoclopramide; Middle Aged; Nausea; Pilot Projects; Serotonin Antagonists; Tropanes; Vomiting

A total of 25 patients (5 groups of 5) were given single i.v. doses of 5, 10, 20, 40 and 60 mg MDL 72,222 (a 5-HT3 receptor antagonist) at 15 minutes before the commencement of a 24-h cisplatin infusion (total dose, 120-200 mg) to determine the efficacy and safety of the former in the prevention of nausea and vomiting associated with such chemotherapy. All patients completed the study. The time to onset of vomiting was significantly correlated with dose. All patients vomited following doses of 5 and 10 mg (range, 1-6 episodes), with onset being noted at 5-8 h. At the 20-mg level, only one episode of vomiting was observed in 3/5 patients, with onset being observed at 18-22 h. Following doses of 40 and 60 mg, 3/10 patients did not vomit; in the remaining patients the number of episodes ranged from 1 to 6, but a significant increase occurred in the time to onset of symptoms. At the higher doses, nausea tended to be milder in nature both at onset and at the time of maximal severity. A similar dose-effect trend was seen in the time to onset of the maximal severity of nausea. The time to and requirement for escape medication was similarly extended at doses of greater than or equal to 20 mg MDL 72,222. Pain at the injection site in one patient was the only unwanted effect associated with MDL 72,222. The results suggest that the i.v. injection of 20 mg MDL 72,222 should be further explored in the control of nausea and vomiting associated with cisplatin administration.

Topics: Adult; Antiemetics; Cisplatin; Drug Evaluation; Female; Humans; Injections, Intravenous; Male; Middle Aged; Nausea; Neoplasms; Serotonin Antagonists; Time Factors; Tropanes; Vomiting