盐酸帕洛诺司琼预防化疗性恶心呕吐的多中心双盲随机对照临床研究

A multicenter,double-blind,randomized control clinical trail of palonosetron hydrochloride injection to prevent chemotherapy-induced nausea and vomitting

目的：奉国家SFDA文，观察和评价国产新药盐酸帕洛诺司琼注射液预防和控制抗肿瘤化疗药物引起的恶心呕吐的有效性和安全性。方法：采用双盲双模拟、随机、阳性药平行对照的多中心临床试验方法。对使用高度致吐性化疗方案的患者，于化疗前半小时缓慢静脉推注新药盐酸帕洛诺司琼注射液0．25mg（试验组）或市售的格拉司琼注射液3mg（对照组）。严格观察患者急性呕吐、延迟性呕吐以及恶心发生情况，必要时给予解救性止吐治疗（格拉司琼＋地塞米松）。结果：6个中心共人组223例患者，试验组111例，对照组112例。试验组对化疗引起的急性呕吐（24小时内）完全缓解率（CRR）与对照组相比无显著性差异（85．59％vs.78．57％，P=0．1420），但前者对化疗引起的延迟性呕吐（24小时-7天）完全控制率（CCR）明显高于对照组（63．96％vs.50．00％，P=0．0282），化疗后未出现呕吐（0—7天）的受试者比例也明显高于对照组（分别为62．16％vs．46．43％，P=0．0140）。同时，帕洛诺司琼注射液控制化疗性恶心的作用优于格拉司琼（P=0．0198）；化疗后人均呕吐发作次数也明显少于格拉司琼[（1．76±4．27）次／例vs．（3．08±6．20）次／例，P=0．0289]。试验组呕吐控制时间明显长于对照组（P=0．0377）。两组在解救治疗的时间、解救治疗的受试者比例、解救治疗人均次数以及KPS评分下降程度方面均无统计学差异（P〉0．05）。两组分别有8．11％和8．04％的受试者出现轻度便秘、腹胀及头痛等（P=1．0000），但是对照组需要服用镇静剂预防焦虑、失眠的受试者明显高于试验组（10．71％vs.0．90％，P=0．0026）。结论：国产新药盐酸帕洛诺司琼注射液预防肿瘤强烈化疗所致恶心呕吐优于盐酸格拉司琼注射液，且安全性好，建议上市应用。

Objective：To observe and assess the efficacy and safety of palonosetron hydrochloride injection made in China for preventing chemotherapy-induced nausea and vomitting in accordance with documents of SFDA. Methods： This study was performed as a multicenter, randomized, double-blind control clinical trial. The patients were randomized to receive a single dose of palonosetron 0. 25 rag（treatment group）, or granisetron 3 mg（ control group）, each administered 30 min before initiation of severely emetogenic chemotherapy. To observe the acute emetic episodes, delay emetic episodes, and nausea, and administer rescue medication （granisetron and dexamethasone） if the patient needed. Results：Two hundred and twenty-three patients form six centers were randomized to the clinical trail, and 111 pts receiving palonosetron, 123 pts receiving granisetron. The proportion of patients with no emetic episodes during the 24 h after chemotherapy administration （acute period） in treatment group and control group weren＇t different （85. 59% vs. 78. 57% ,P =0. 142 0） ,but the proportion of patients with no emetic episodes during delay （24h-7 days post-chemotherapy） and overall （0-7 days） periods were higher in the treatment group than those of in the control group （63. 96% vs. 50. 00%, P = 0. 028 2; 62. 16% vs. 46. 43% ,P=0. 014 0）. Palonosetron was superior to granisetron in control of nausea（P =0. 019 8）. The number of emetic episodes in the treatment group wasn＇t so many as that of the control group （ average ： 1.76 ± 4. 27 times/case vs. 3.08± 6. 20 times/case ,P = 0. 028 9）. The time to emetic episodes in the treatment group was longer than in the control group（ P = 0. 037 7 ）. The time to rescue medication, the proportion of patients with rescue medication, the times of rescue medication and the degree of KPS score declining weren＇t significant deviation. 8.11% and 8.04% of patients in the treatment group and control group appeared lightly constipation, abdominal siatention and headache （ P = 1. 000 0 ） ; but more patients demanded temporantia for anxiety and agrypnia in the control group（0. 90% vs. 10. 71% ,P =0. 002 6）. Condusion：Palonosetron hydrochloride injection is superior to granisetron for preventing chemotherapy-induced vomitting and nauesa, and it is safer than granisetron.