title: Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial.
abstract: Combinations of metoclopramide and dexamethasone given intravenously control vomiting caused by high doses of cisplatin. Lorazepam and diphenhydramine are useful adjuncts to antiemetics. In a double-blind trial, 120 patients receiving high-dose cisplatin (120 mg/m2) for the first time were randomly assigned to receive either lorazepam (1.5 mg/m2) or diphenhydramine (50 mg) intravenously, 45 minutes prior to cisplatin. In addition, all patients received intravenous dexamethasone (20 mg) 40 minutes prior to chemotherapy along with metoclopramide (3 mg/kg) 30 minutes before and 90 minutes after cisplatin. Patients were directly observed in the hospital after cisplatin administration and completed a subjective assessment questionnaire. Overall, 60% of patients experienced no vomiting, and 83% had two or fewer emetic episodes during the study. There were no significant differences in objective antiemetic control between the two regimens. Only 3% of patients receiving lorazepam experienced treatment-related restlessness as opposed to 19% given diphenhydramine (P = 0.007). Less recall of chemotherapy administration (P less than 0.001), more sedation (P = 0.003), and transient enuresis while sedated (P = 0.0002) were characteristic of patients receiving lorazepam. Patient-generated ratings revealed less anxiety (P = 0.0001) for those individuals given the lorazepam-containing combination. Both regimens were well accepted, with 89% of patients receiving the lorazepam combination and 83% of those given the diphenhydramine regimen wishing to receive the same drugs in the future. Some degree of delayed vomiting occurred in 85% of patients during the 4-day period following this study. During the time that patients are at the greatest risk for emesis, the 24 hours immediately following cisplatin, three drug antiemetic combinations of either lorazepam or diphenhydramine with metoclopramide plus dexamethasone stopped cisplatin-induced emesis for the majority of patients and lessen other treatment-related side effects. Less restlessness and anxiety were observed among individuals receiving the lorazepam-containing combination.
authors.affiliation: Department of Medicine, Sloan-Kettering Cancer Center, New York, New York.
authors.forename: M G
authors.initials: MG
authors.lastname: Kris
authors.forename: R J
authors.initials: RJ
authors.lastname: Gralla
authors.forename: R A
authors.initials: RA
authors.lastname: Clark
authors.forename: L B
authors.initials: LB
authors.lastname: Tyson
authors.forename: S
authors.initials: S
authors.lastname: Groshen
mesh_terms: D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage*; D004155:Diphenhydramine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage*; D008297:Male; D008568:Memory / Q000187:drug effects; D008787:Metoclopramide / Q000008:administration & dosage*; D008875:Middle Aged; D011897:Random Allocation; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D003907:Dexamethasone; D004155:Diphenhydramine; D008787:Metoclopramide; D008140:Lorazepam; D002945:Cisplatin