Malik I A, Khan W A, Qazilbash M, Ata E, Butt A, Khan M A
Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan.
Am J Clin Oncol. 1995 Apr;18(2):170-5. doi: 10.1097/00000421-199504000-00017.
Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy. Cisplatin induces anticipatory and acute, as well as, delayed emesis. High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70% of cases. Several agents, including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects. Lorazepam, a benzodiazepine, has both antiemetic and anxiolytic properties. It can be useful as an adjunct to metoclopramide-based therapy. We conducted a randomized trial to evaluate the efficacy of lorazepam in managing anticipatory, acute, and delayed emesis induced by high doses of cisplatin. A total of 180 events involving cisplatin administration (100 mg/m2 as a 24-hour continuous infusion) were randomized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam. Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy. All episodes are evaluable. Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting (P < .05) as well as acute emesis (P = .05) induced by cisplatin. Delayed emesis was also decreased; however, it was statistically significant on day 3 only (P < .05). Side effects were few except for mild sedation and amnesia, which were significantly more common in those receiving lorazepam (P < .001). We conclude that lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory, acute, and delayed nausea and vomiting. This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists.
恶心和呕吐是高剂量顺铂治疗极为常见且最令人痛苦的副作用。顺铂会引发预期性、急性以及迟发性呕吐。高剂量的甲氧氯普胺可有效减轻这些症状的严重程度，在高达70%的病例中有效。包括地塞米松和抗组胺药在内的几种药物已被证明可提高甲氧氯普胺的疗效或减少其副作用。劳拉西泮作为一种苯二氮䓬类药物，具有止吐和抗焦虑特性。它可用作基于甲氧氯普胺治疗的辅助药物。我们进行了一项随机试验，以评估劳拉西泮在处理高剂量顺铂引起的预期性、急性和迟发性呕吐方面的疗效。总共180例涉及顺铂给药（100 mg/m²，24小时持续输注）的病例被随机分组，分别接受甲氧氯普胺联合地塞米松和氯马斯汀，其中部分组加用或不加用劳拉西泮。使用分类量表记录恶心、呕吐的发生率以及与止吐治疗相关的副作用。所有发作均具有可评估性。劳拉西泮显著降低了顺铂引起的预期性恶心和呕吐的发生率（P <.05）以及急性呕吐的发生率（P =.05）。迟发性呕吐也有所减少；然而，仅在第3天具有统计学意义（P <.05）。除了轻度镇静和失忆外，副作用较少，而这些在接受劳拉西泮的患者中明显更常见（P <.001）。我们得出结论，劳拉西泮可提高甲氧氯普胺对顺铂引起的预期性、急性和迟发性恶心和呕吐的疗效。这种四联药物方案可能是在与新引入的5-羟色胺拮抗剂进行对比试验中可采用的最佳组合之一。
