新型5-羟色胺3（5-HT3）受体拮抗剂帕洛诺司琼可改善对中度致吐性化疗引起的恶心和呕吐的预防：一项与多拉司琼对比的III期单剂量试验结果

Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron.

作者信息

Eisenberg Peter, Figueroa-Vadillo Jazmin, Zamora Rosalio, Charu Veena, Hajdenberg Julio, Cartmell Alan, Macciocchi Alberto, Grunberg Steven

机构信息

California Cancer Care, Greenbrae, California, USA.

出版信息

Cancer. 2003 Dec 1;98(11):2473-82. doi: 10.1002/cncr.11817.

DOI:10.1002/cncr.11817

PMID:14635083

Abstract

BACKGROUND

Palonosetron, a highly selective and potent 5-HT(3) receptor antagonist with a strong binding affinity and a long plasma elimination half-life (approximately 40 hours), has shown efficacy in Phase II trials in preventing chemotherapy-induced nausea and vomiting (CINV) resulting from highly emetogenic chemotherapy. The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy.

METHODS

In the current study, 592 patients were randomized to receive a single, intravenous dose of palonosetron 0.25 mg, palonosetron 0.75 mg, or dolasetron 100 mg, 30 minutes before receiving moderately emetogenic chemotherapy. The primary efficacy endpoint was the proportion of patients with a complete response (CR; defined as no emetic episodes and no rescue medication) during the first 24 hours after chemotherapy. Secondary endpoints included assessment of prevention of delayed emesis (2-5 days postchemotherapy).

RESULTS

In the current study, 569 patients received study medication and were included in the intent-to-treat efficacy analyses. CR rates during the first 24 hours were 63.0% for palonosetron 0.25 mg, 57.1% for palonosetron 0.75 mg, and 52.9% for dolasetron 100 mg. CR rates during the delayed period (24-120 hours after chemotherapy) were superior for palonosetron compared with dolasetron. Adverse events (AEs) were mostly mild to moderate and not related to study medication, with similar incidences among groups. There were no serious drug-related AEs.

CONCLUSIONS

A single dose of palonosetron is as effective as a single dose of dolasetron in preventing acute CINV and superior to dolasetron in preventing delayed CINV after moderately emetogenic chemotherapy, with a comparable safety profile for all treatment groups.

摘要

背景

帕洛诺司琼是一种高选择性、强效的5-羟色胺（5-HT）3受体拮抗剂，具有很强的结合亲和力和较长的血浆消除半衰期（约40小时），在II期试验中已显示出对预防由高致吐性化疗引起的化疗所致恶心和呕吐（CINV）有效。当前的III期试验评估了帕洛诺司琼在预防中度致吐性化疗后急性和迟发性CINV方面的疗效和安全性。

方法

在本研究中，592例患者在接受中度致吐性化疗前30分钟被随机分配接受单次静脉注射0.25mg帕洛诺司琼、0.75mg帕洛诺司琼或100mg多潘立酮。主要疗效终点是化疗后首24小时内完全缓解（CR；定义为无呕吐发作且未使用解救药物）的患者比例。次要终点包括对迟发性呕吐（化疗后2 - 5天）预防情况的评估。

结果

在本研究中，569例患者接受了研究用药并纳入意向性治疗疗效分析。首24小时内，0.25mg帕洛诺司琼组的CR率为63.0%，0.75mg帕洛诺司琼组为57.1%，100mg多潘立酮组为52.9%。在迟发期（化疗后24 - 120小时），帕洛诺司琼组的CR率优于多潘立酮组。不良事件（AE）大多为轻度至中度，且与研究用药无关，各组发生率相似。未出现严重的药物相关AE。