CAJ | 학술논문

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。目的觀察和評價國產新藥鹽痠帕洛諾司瓊膠囊預防和控製化療藥物引起的噁心、嘔吐的有效性和安全性。方法採用隨機、暘性藥平行對照、雙盲、雙模擬的多中心臨床試驗方法，對使用中度緻吐性化療方案的噁性腫瘤患者，于第1天化療前1h口服鹽痠帕洛諾司瓊膠囊1粒（0?5mg／粒）和鹽痠格拉司瓊分散片模擬劑1片（試驗組）或口服鹽痠格拉司瓊分散片1片（1mg／片）和鹽痠帕洛諾司瓊膠囊的模擬劑1粒（對照組），化療12h後試驗組和對照組分彆再次給予鹽痠格拉司瓊分散片模擬劑1片和鹽痠格拉司瓊分散片1片（1mg／片）。觀察用藥噹天至化療後5天患者齣現急性噁心嘔吐、延遲性噁心嘔吐、體力狀況變化情況和對噁心嘔吐控製的滿意程度VAS評分，必要時給予格拉司瓊＋地塞米鬆的解救性止吐治療。結果7傢研究中心共入組240例患者，試驗組122例，對照組118例。經全數據分析集（ FAS）分析，試驗組與對照組急性嘔吐的完全有效率差異無統計學意義（86?89％ vs．85?47％，P＝0?8338），經非劣效檢驗，試驗組不亞于對照組（95％CI下界值＝－7?33％，u＝2?558，P＝0?0105）。經符閤方案數據集（ PPS）分析，兩組延遲性嘔吐的完全控製率差異有統計學意義（74?38％vs．61?54％，P＝0?0490）。整箇觀察期內試驗組的嘔吐髮生率為21?31％，明顯低于對照組的33?33％（ P＝0?0422）。化療第2天試驗組與對照組齣現嘔吐的患者嘔吐次數（次／例）分彆為0?15±0?52和0?31±0?68，差異有統計學意義（P＝0?0090）；化療第1～5天兩組0級噁心髮生率和PS評分的差異均無統計學意義（ P＞0?05）；化療第2～4天兩組VAS評分的差異均有統計學意義（ P＜0?05）。試驗組髮生便祕和總膽紅素升高各2例，對照組髮生便祕4例和藥物性皮炎1例，兩組不良反應的髮生率分彆為3?28％和4?24％（ P＞0?05）。結論國產鹽痠帕洛諾司瓊膠囊在預防中度緻吐性化療所緻的急性噁心、嘔吐與鹽痠格拉司瓊分散片療效相噹，而對延遲性嘔吐的療效優于鹽痠格拉司瓊分散片，且安全性好，給藥方便，建議準予上市應用。
목적관찰화평개국산신약염산파락낙사경효낭예방화공제화료약물인기적악심、구토적유효성화안전성。방법채용수궤、양성약평행대조、쌍맹、쌍모의적다중심림상시험방법，대사용중도치토성화료방안적악성종류환자，우제1천화료전1h구복염산파락낙사경효낭1립（0?5mg／립）화염산격랍사경분산편모의제1편（시험조）혹구복염산격랍사경분산편1편（1mg／편）화염산파락낙사경효낭적모의제1립（대조조），화료12h후시험조화대조조분별재차급여염산격랍사경분산편모의제1편화염산격랍사경분산편1편（1mg／편）。관찰용약당천지화료후5천환자출현급성악심구토、연지성악심구토、체력상황변화정황화대악심구토공제적만의정도VAS평분，필요시급여격랍사경＋지새미송적해구성지토치료。결과7가연구중심공입조240례환자，시험조122례，대조조118례。경전수거분석집（ FAS）분석，시험조여대조조급성구토적완전유효솔차이무통계학의의（86?89％ vs．85?47％，P＝0?8338），경비렬효검험，시험조불아우대조조（95％CI하계치＝－7?33％，u＝2?558，P＝0?0105）。경부합방안수거집（ PPS）분석，량조연지성구토적완전공제솔차이유통계학의의（74?38％vs．61?54％，P＝0?0490）。정개관찰기내시험조적구토발생솔위21?31％，명현저우대조조적33?33％（ P＝0?0422）。화료제2천시험조여대조조출현구토적환자구토차수（차／례）분별위0?15±0?52화0?31±0?68，차이유통계학의의（P＝0?0090）；화료제1～5천량조0급악심발생솔화PS평분적차이균무통계학의의（ P＞0?05）；화료제2～4천량조VAS평분적차이균유통계학의의（ P＜0?05）。시험조발생편비화총담홍소승고각2례，대조조발생편비4례화약물성피염1례，량조불량반응적발생솔분별위3?28％화4?24％（ P＞0?05）。결론국산염산파락낙사경효낭재예방중도치토성화료소치적급성악심、구토여염산격랍사경분산편료효상당，이대연지성구토적료효우우염산격랍사경분산편，차안전성호，급약방편，건의준여상시응용。
Objective To observe and evaluate the efficacy and safety of palonosetron hydrochloride capsules made in China for prevention of chemotherapy?induced nausea and vomiting. Methods This study was performed as a multicenter, randomized, double?blind control clinical trial. The patients were randomized to administer palonosetron hydrochloride capsule( 0?5mg) and a simu?lator of granisetron dispersible tablet(experimental group), or a granisetron dispersible tablet(1mg) and a simulator of palonosetron ( control group) , each administered 1 hour before initiation of moderate emetogenic chemotherapy. After 12h for chemotherapy, experi?mental group were administered a simulator of granisetron dispersible tablet and control group were administered a granisetron dispers?ible tablet ( 1mg) . The acute emetic episodes, delayed emetic episodes, nausea, physical status and VAS scores was recorded, admin?ister rescue medication ( granisetron combined with dexamethasone) was taken if patients needed. Results A total of 240 patients from seven clinical research centers in China were randomized to the clinical trial with 122 patients in experimental group and 118 patients in control group. The proportion of patients with emetic episodes overall periods ( 0?7days) was lower in experimental group than in control group (21?31% vs.33?33%, P=0?0422). The proportion of patients with no emetic episodes during the 24h after chemotherapy ad?ministration ( acute period ) between experimental group and control group was no significant difference through full analysis set (86?89% vs.85?47%, P=0?8338), and the proportion of patients with no emetic episodes during delay (24h?7days post?chemothera?py) between experimental group and control group was significant difference through per?protocol set analysis( 74?38% vs. 61?54%, P=0?0490). The average vomiting times of experimental group and control group were 0?15±0?52 and 0?31±0?68 respectively in sec?ond day of chemotherapy(P=0?0090). There were no significant difference for rates of grade 0 nausea and PS scores between two groups in 1?5 days of chemotherapy( P>0?05) , except to VAS scores in 2?4 days of chemotherapy( P<0?05) . The adverse reactions of experimental group and control group included constipation( 2 cases) , total bilirubin( 2 cases) and constipation( 4 cases) , drug derma?titis(1 case),respectively. The adverse reaction rates between two groups were 3?28% and 4?24% respectively(P>0?05). Conclusion <br> Palonosetron hydrochloride capsule is similar to granisetron for preventing chemotherapy?induced acute nausea and vomiting, and su?perior to granisetron for delayed nausea and vomiting. Palonosetron hydrochloride capsule is safe and convenient administration.