Seynaeve C, De Mulder P H, Verweij J, Gralla R J
Department of Medical Oncology, Rotterdam Cancer Institute/Dr. Daniel den Hoed Clinic, The Netherlands.
Pharm Weekbl Sci. 1991 Oct 18;13(5):189-97. doi: 10.1007/BF01988874.
Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3-6 mg.kg-1.d-1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy.
细胞毒性化疗可诱发急性、迟发性和预期性恶心与呕吐。本文综述了现有止吐药的疗效和毒性数据及其在化疗所致呕吐中的作用。此外,还阐述了止吐试验方法中的一些缺陷以及已知影响患者对致吐刺激个体敏感性的因素。到目前为止,高剂量甲氧氯普胺(3 - 6毫克·千克⁻¹·天⁻¹)是控制急性呕吐最有效的单一药物。然而,其多巴胺拮抗作用引起的锥体外系反应仍是一个主要缺点。加用地塞米松和/或劳拉西泮可降低锥体外系反应的发生率,并进一步改善止吐控制效果。在动物实验中,5-羟色胺3型受体拮抗剂已显示出对化疗和放疗所致呕吐有良好的止吐效果;临床研究结果有待观察。迟发性恶心和呕吐尚未得到广泛研究。目前,甲氧氯普胺和地塞米松联合使用可为约50%接受顺铂化疗的患者提供最佳保护。预期性恶心和呕吐仍然是主要问题,且缺乏有效的药物治疗方法。控制这类呕吐的尝试主要集中在具有遗忘特性的药物和行为疗法上。