Perez E A
Department of Medicine, University of California, Davis, Sacramento, USA.
J Clin Oncol. 1995 Apr;13(4):1036-43. doi: 10.1200/JCO.1995.13.4.1036.
This analysis was undertaken to review published reports of the comparative efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in the prophylaxis of acute chemotherapy-induced emesis.
Comparison data used are the preclinical pharmacology as well as the design and results of clinical trials. Seven comparative studies that used granisetron, ondansetron, or tropisetron in patients who received either moderately or highly emetogenic chemotherapy are reviewed. As the study designs, patient population, chemotherapy, antiemetic doses and schedule, and methods of assessment were slightly different, the results of each study are analyzed independently. Effectiveness is assessed by emetic episodes, nausea, and patient preference.
The preclinical pharmacologic profile is different among the 5-HT3 antagonists in terms of potency, selectivity, dose response, and duration of action. The comparative clinical trials show that a single intravenous (i.v.) dose of granisetron 3 mg is as effective as multiple (8 mg x 3) or single (32 mg) i.v. doses of ondansetron for the prevention of acute nausea and emesis due to cisplatin. In the two moderately emetogenic clinical trials, granisetron 3 mg i.v. was at least as effective as ondansetron 8 mg i.v. +/- 24 mg orally and tropisetron 5 mg i.v. Patient preference was evaluated in three of the four crossover trials: granisetron was preferred in three of four, and no preference was reported in the fourth. The one trial to compare ondansetron 0.15 mg/kg x 3 versus granisetron 10 micrograms/kg x 1 or granisetron 40 micrograms/kg i.v. demonstrated equivalent control of nausea and vomiting in patients who received cisplatin-based chemotherapy.
The 5-HT3 receptor antagonists compared are highly effective antiemetic agents that have now become the standard of care for preventing chemotherapy-induced emesis. Whether the described preclinical differences among these agents are also clinically significant remains to be seen. In the comparative trials analyzed, the 5-HT3 receptor antagonists demonstrated relatively equivalent clinical efficacy. Cost analysis may favor the use of one agent over another depending on the emetogenic challenge, dose of the 5-HT3 antagonists, and number of doses recommended. Patient preference may be an important factor to be considered in future antiemetic trials.
进行此项分析以回顾已发表的关于5-羟色胺-3（5-HT3）受体拮抗剂预防急性化疗所致呕吐的比较疗效和安全性的报告。
所使用的比较数据包括临床前药理学以及临床试验的设计和结果。回顾了七项比较研究，这些研究在接受中度或高度致吐性化疗的患者中使用了格拉司琼、昂丹司琼或托烷司琼。由于研究设计、患者群体、化疗、止吐剂量和给药方案以及评估方法略有不同，对每项研究的结果进行独立分析。通过呕吐发作、恶心程度和患者偏好来评估有效性。
5-HT3拮抗剂在效力、选择性、剂量反应和作用持续时间方面的临床前药理学特征有所不同。比较临床试验表明，静脉注射3毫克格拉司琼的单次剂量与静脉注射多次（8毫克×3）或单次（32毫克）昂丹司琼预防顺铂所致急性恶心和呕吐的效果相同。在两项中度致吐性临床试验中，静脉注射3毫克格拉司琼的效果至少与静脉注射8毫克昂丹司琼±口服24毫克以及静脉注射5毫克托烷司琼相同。在四项交叉试验中的三项中评估了患者偏好：四项中有三项更倾向于格拉司琼，第四项未报告偏好情况。一项比较静脉注射0.15毫克/千克×3的昂丹司琼与静脉注射10微克/千克×1或静脉注射40微克/千克格拉司琼的试验表明，在接受以顺铂为基础的化疗的患者中，对恶心和呕吐的控制效果相当。
所比较的5-HT3受体拮抗剂是高效的止吐药物，现已成为预防化疗所致呕吐的护理标准。这些药物在临床前描述的差异是否也具有临床意义还有待观察。在所分析的比较试验中，5-HT3受体拮抗剂显示出相对等效的临床疗效。成本分析可能会根据致吐挑战、5-HT3拮抗剂的剂量和推荐的给药次数而倾向于使用一种药物而非另一种。患者偏好可能是未来止吐试验中要考虑的一个重要因素。
