Kris M G, Gralla R J, Clark R A, Tyson L B, Groshen S
Department of Medicine, Sloan-Kettering Cancer Center, New York, New York.
Cancer. 1987 Dec 1;60(11):2816-22. doi: 10.1002/1097-0142(19871201)60:11<2816::aid-cncr2820601137>3.0.co;2-7.
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.
静脉注射胃复安和地塞米松的联合用药可控制高剂量顺铂引起的呕吐。劳拉西泮和苯海拉明是有效的止吐辅助药物。在一项双盲试验中，120例首次接受高剂量顺铂（120mg/m²）治疗的患者被随机分配在顺铂给药前45分钟静脉注射劳拉西泮（1.5mg/m²）或苯海拉明（50mg）。此外，所有患者在化疗前40分钟静脉注射地塞米松（20mg），并在顺铂给药前30分钟及给药后90分钟静脉注射胃复安（3mg/kg）。顺铂给药后患者在医院接受直接观察，并完成一份主观评估问卷。总体而言，60%的患者未出现呕吐，83%的患者在研究期间呕吐发作次数为两次或更少。两种治疗方案在客观止吐控制方面无显著差异。接受劳拉西泮治疗的患者中只有3%出现与治疗相关的烦躁不安，而接受苯海拉明治疗的患者中这一比例为19%（P=0.007）。接受劳拉西泮治疗的患者具有化疗给药回忆较少（P<0.001）、镇静作用更强（P=0.003）以及镇静时短暂遗尿（P=0.0002）的特点。患者自评显示，接受含劳拉西泮联合用药的患者焦虑程度较低（P=0.0001）。两种治疗方案均被广泛接受，接受含劳拉西泮联合用药的患者中有89%以及接受苯海拉明治疗方案的患者中有83%希望在未来继续使用相同药物。在本研究后的4天内，85%的患者出现了一定程度的延迟性呕吐。在患者发生呕吐风险最高的时间段，即顺铂给药后的24小时内，劳拉西泮或苯海拉明与胃复安加地塞米松组成的三联止吐药物组合使大多数患者停止了顺铂诱导的呕吐，并减轻了其他与治疗相关的副作用。接受含劳拉西泮联合用药的患者中观察到较少的烦躁不安和焦虑。
