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目的观察和评价国产新药盐酸帕洛诺司琼胶囊预防和控制化疗药物引起的恶心、呕吐的有效性和安全性。方法采用随机、阳性药平行对照、双盲、双模拟的多中心临床试验方法,对使用中度致吐性化疗方案的恶性肿瘤患者,于第1天化疗前1h口服盐酸帕洛诺司琼胶囊1粒(0.5mg/粒)和盐酸格拉司琼分散片模拟剂1片(试验组)或口服盐酸格拉司琼分散片1片(1mg/片)和盐酸帕洛诺司琼胶囊的模拟剂1粒(对照组),化疗12h后试验组和对照组分别再次给予盐酸格拉司琼分散片模拟剂1片和盐酸格拉司琼分散片1片(1mg/片)。观察用药当天至化疗后5天患者出现急性恶心呕吐、延迟性恶心呕吐、体力状况变化情况和对恶心呕吐控制的满意程度VAS评分,必要时给予格拉司琼+地塞米松的解救性止吐治疗。结果 7家研究中心共入组240例患者,试验组122例,对照组118例。经全数据分析集(FAS)分析,试验组与对照组急性呕吐的完全有效率差异无统计学意义(86.89%vs.85.47%,P=0.8338),经非劣效检验,试验组不亚于对照组(95%CI下界值=-7.33%,u=2.558,P=0.0105)。经符合方案数据集(PPS)分析,两组延迟性呕吐的完全控制率差异有统计学意义(74.38%vs.61.54%,P=0.0490)。整个观察期内试验组的呕吐发生率为21.31%,明显低于对照组的33.33%(P=0.0422)。化疗第2天试验组与对照组出现呕吐的患者呕吐次数(次/例)分别为0.15±0.52和0.31±0.68,差异有统计学意义(P=0.0090);化疗第1~5天两组0级恶心发生率和PS评分的差异均无统计学意义(P>0.05);化疗第2~4天两组VAS评分的差异均有统计学意义(P<0.05)。试验组发生便秘和总胆红素升高各2例,对照组发生便秘4例和药物性皮炎1例,两组不良反应的发生率分别为3.28%和4.24%(P>0.05)。结论国产盐酸帕洛诺司琼胶囊在预防中度致吐性化疗所致的急性恶心、呕吐与盐酸格拉司琼分散片疗效相当,而对延迟性呕吐的疗效优于盐酸格拉司琼分散片,且安全性好,给药方便,建议准予上市应用。
Objective To observe and evaluate the efficacy and safety of the domestic new drug palonosetron hydrochloride capsule in the prevention and control of nausea and vomiting caused by chemotherapy drugs. Methods A randomized, positive drug parallel control, double-blind, double-dummy, multi-center clinical trial was conducted on patients with malignant tumors using a moderate emetic chemotherapy regimen. On the first day before chemotherapy, palonosetron hydrochloride capsules 1 tablet (0.5 mg / tablet) and 1 tablet of granisetron hydrochloride dispersible tablet simulant (test group) or 1 tablet of granisetron hydrochloride dispersible tablet (1 mg / tablet) and simulant 1 of palonosetron hydrochloride capsule Granules (control group) were treated with granisetron hydrochloride dispersible tablet simulant 1 tablet and granisetron hydrochloride dispersible tablet 1 tablet (1 mg / tablet) respectively after 12 hours of chemotherapy. Observed the day of treatment to 5 days after chemotherapy in patients with acute nausea and vomiting, delayed nausea and vomiting, physical status changes and satisfaction with the control of nausea and vomiting VAS score, if necessary, given granisetron dexamethasone rescue antiemetic treatment . Results A total of 240 patients were enrolled in 7 research centers, 122 in the experimental group and 118 in the control group. There was no significant difference in the total effective rate of acute vomiting between experimental group and control group (F = 86.89% vs 85.47%, P = 0.8338). After non-inferiority test, Control group (95% CI lower bound = -7.33%, u = 2.558, P = 0.0105). The complete control rate of delayed vomiting in the two groups was statistically significant (74.38% vs.61.54%, P = 0.0490) after complying with the PPS data. The incidence of vomiting in the experimental group was 21.31% during the whole observation period, which was significantly lower than 33.33% in the control group (P = 0.0422). On the second day after chemotherapy, the number of vomiting (times / cases) in the vomiting group was 0.15 ± 0.52 and 0.31 ± 0.68 in the test group and the control group, respectively, with significant difference (P = 0.0090) There was no significant difference in the incidence of nausea and PS between the two groups (P> 0.05). There was significant difference in VAS scores between the two groups on the 2nd and 4th days after chemotherapy (P <0.05). Two cases of constipation and total bilirubin were found in experimental group, four cases of constipation and one case of drug dermatitis in control group. The incidence of adverse reactions in both groups were 3.28% and 4.24%, respectively (P> 0.05). Conclusion Palonosetron hydrochloride capsules in the prevention of moderate emetogenic chemotherapy induced acute nausea, vomiting and granisetron hydrochloride dispersible tablets comparable, and the efficacy of delayed vomiting better than granisetron hydrochloride dispersible tablets, And good security, convenient administration, it is recommended to grant listing application.