Thirty-seven patients with advanced incurable malignancies who were receiving their first course of cisplatin (2 90 mg/mz bolus), alone or in combination with other antineoplastic agents, were entered in this randomized, double-blind study to determine the antiemetic efficacy of the addition of high-dose dexamethasone to lorazepam plus metoclopramide. All patients received lorazepam (1.5 mg/mz) and metoclopramide (2.0 mg/kg) intravenously (IV) 30 minutes before cisplatin, with the same dose of metoclopramide repeated 1.5, 3.5, 6.5, and 9.5 hours after the 30-minute cisplatin infusion. Patients were randomized to receive dexamethasone (0.5 mg/kg) or placebo by slow bolus injection 30 minutes before cisplatin. All patients were hospitalized for 24 hours and evaluated by observation after cisplatin and a patient questionnaire before discharge. Eighteen patients received metoclopramide and lorazepam without dexamethasone: six (33%) reported no vomiting and four (22%) reported no nausea or vomiting. Nineteen patients also received dexamethasone: 14 (74%) had no vomiting and 13 (68%) reported no nausea or vomiting. These differences were statistically significantly different (P = 0.013 and 0.005, respectively). The side effects attributable to the antiemetic regimen were somnolence (loo%), confusion (a%), and diarrhea (46%), and were the same in both arms. Dexamethasone significantly improved the antiemetic efficacy of metoclopramide plus lorazepam without adding toxicity. This three-drug combination gave a high rate of control of acute emesis induced by high-dose cisplatin. Cancer 66:443-446, 1990. ISPLATIN IS AN EFFECTIVE antineoplastic agent for C a number of solid tumors.' However, a patient's quality of life and acceptance of therapy may be severely hampered by drug-induced nausea and vomiting. Studies have shown that high-dose intravenous (IV) metoclo-pramide is a more effective antiemetic agent than placebo or conventional-dose prochlorperazine in patients receiving cisplatin.2 However, only 20% to 40% of patients are rendered symptom-free in the immediate postdrug period by single-agent met~clopramide.~.~ Lorazepam and dexamethasone have been shown to have significant antiemetic activity and high patient acceptance as single agents, and the side effects of these two agents are dissimilar enough from those produced by metoclopramide to permit combination drug administration without requiring dose Two-drug combinations of metoclopramide and dexamethasone and metoclopramide and lorazepam have shown improved antiemetic effect compared with single-agent metoclopra-mide.3,s This study was undertaken to determine the an-tiemetic efficacy of metoclopramide and lorazepam with or without dexamethasone in patients receiving high-dose cisplatin, and to compare the two-drug regimen with the three-drug regimen. Patients and Methods During a 10-month period, 39 consecutive patients who met all eligibility criteria were offered study participation. 443
