比較甲氧氯普胺與阿瑞匹坦預(yù)防延遲性化療致惡心嘔吐的臨床研究
發(fā)布時間：2018-08-22 19:10
【摘要】：研究背景嘔吐(Chemotherapy-induced nausea and vomiting,CINV)是化療中最常見的副反應(yīng)之一,5-HT3受體拮抗劑、NK-1受體拮抗劑及地塞米松是預(yù)防高致吐性化療所致CINV的有效藥物。但NK-1受體拮抗劑阿瑞匹坦價格相對較高,且仍有約25～35%接受HEC的患者使用阿瑞匹坦后在延遲期(化療后24～120小時)CINV未能得到有效緩解。因此,尋找其他有效藥物來預(yù)防延遲性CINV是目前臨床面臨的重要問題。近期Rolia等進(jìn)行的一項臨床研究結(jié)果顯示,在控制延遲期嘔吐中甲氧氯普胺聯(lián)合地塞米松所產(chǎn)生的療效并不劣于阿瑞匹坦聯(lián)合地塞米松(完全緩解率82.5%vs 80.3%,P0.05)。該研究給延遲性CINV帶來了新的選擇,但存在以下兩點不足:一、Rolia等研究在急性期(化療后0～24h)均使用了阿瑞匹坦,可能影響后續(xù)甲氧氯普胺對延遲期CINV的作用;二、在Rolia等研究中甲氧氯普胺的日劑量是80mg,而我國止吐指南推薦用法是每日10～40mg。中國人體表面積較歐洲人小,甲氧氯普胺日劑量40mg能否有效控制延遲期嘔吐有待進(jìn)一步臨床研究證實。研究目的比較甲氧氯普胺與阿瑞匹坦在聯(lián)合地塞米松基礎(chǔ)上預(yù)防HEC引起的延遲性惡心嘔吐的療效和安全性。同時也探索在三聯(lián)止吐方案中,兩代5-HT3受體拮抗劑對預(yù)防HEC中CINV的療效和安全性。研究方法將在接受HEC治療的惡性實體瘤患者,隨機(jī)分配到四個止吐方案組,MPD組的止吐方案為甲氧氯普胺20mgbidd2～4;帕洛諾司瓊0.25mgd1;地塞米松20mgd1,8mgbidd2～4。APD組的止吐方案為阿瑞匹坦125mgd1,80mg d2～3;帕洛諾司瓊0.25mgd1;地塞米松12mgd1,8mgd2～4。ATD組的止吐方案為阿瑞匹坦125mgd1,80mgd2～3;托烷司瓊5mgd1;地塞米松12mg d1,8mg d2～4。PD組的止吐方案為帕洛諾司瓊0.25mg d1;地塞米松12mg d1,8mg d2～4。主要研究終點是完全緩解的患者百分比(CRR),次要研究終點是無嘔吐、完全控制(無嘔吐及無解救性止吐治療、無輕度以上惡心)、無惡心及不良反應(yīng)發(fā)生的患者百分比。研究結(jié)果從2015年7月至2017年1月,一共納入127名患者,其中126名患者可評估。1、MPD組、APD組及PD組在延遲期獲得的完全緩解率分別為87.1%、81.3%、71.9%,差異無統(tǒng)計學(xué)意義(P0.05)。對于惡心的控制,APD組在總體期的完全控制率最高,為78.1%,其次為MPD組(74.2%),最后為PD組(68.8%)。無惡心的發(fā)生率在MPD組、APD組及PD組分別為48.4%、46.9%及46.9%,差異無統(tǒng)計學(xué)意義(P0.05)。2、APD組與ATD組在總體期獲得的完全緩解率分別為81.3%、77.4%,差異無統(tǒng)計學(xué)意義(P =0.707)。而在急性期和延遲期APD組與ATD組獲得的完全緩解率分別為96.9%vs 93.5%、81.3%vs 77.4%,差異均無統(tǒng)計學(xué)意義(P0.05)。對于惡心的控制,APD組與ATD組在總體期的完全控制率和無惡心率分別為 78.1%vs 74.2%(P0.05)、46.9%vs 41.9%(P0.05)。3、四組主要不良反應(yīng)為便秘、乏力及呃逆,不良反應(yīng)發(fā)生率無統(tǒng)計學(xué)意義(P0.05),患者均可以耐受。研究結(jié)論甲氧氯普胺聯(lián)合帕洛諾司瓊及地塞米松的止吐方案,與標(biāo)準(zhǔn)的三聯(lián)止吐方案(阿瑞匹坦、帕洛諾司瓊及地塞米松)相比,兩組止吐方案在HEC中具有相似的療效及安全性。同時,還發(fā)現(xiàn)含帕洛諾司瓊的三聯(lián)止吐方案在預(yù)防HEC中CINV的療效與含托烷司瓊的三聯(lián)止吐方案相似。
[Abstract]:Background Chemotherapy-induced nausea and vomiting (CINV) is one of the most common side effects of chemotherapy. 5-HT3 receptor antagonists, NK-1 receptor antagonists and dexamethasone are effective drugs for preventing CINV induced by hyperemetic chemotherapy. However, NK-1 receptor antagonist aspirin is relatively expensive and about 25-35% of patients still receive HEC. CINV did not respond effectively to aspirin in the delayed phase (24-120 hours after chemotherapy). Therefore, finding other effective drugs to prevent delayed CINV is an important clinical problem. A recent clinical study conducted by Rolia et al. showed that metoclopramide combined with dexamethasone in the control of delayed vomiting. This study provides new options for delayed CINV, but there are two shortcomings. First, Rolia et al. studied the use of aspirin in the acute phase (0-24 hours after chemotherapy), which may affect the follow-up effect of metoclopramide on delayed CINV. Second, the daily dose of metoclopramide in Rolia and other studies is 80 mg, while the recommended prescription in China is 10-40 mg daily. The surface area of Chinese people is smaller than that of Europeans. Whether the daily dose of metoclopramide 40 mg can effectively control delayed vomiting remains to be confirmed by further clinical studies. The efficacy and safety of two-generation 5-HT3 receptor antagonists in the triple antiemetic regimen for the prevention of CINV in HEC were also explored. The antiemetic regimens of methoxyclopramine 20 mg bid 2-4, palonosetron 0.25 mg gd1, dexamethasone 20 mg bid 2-4, and dexamethasone 20 mg bid 2-4 were aspirin 125 mg gd1, 80 mg D 2-3, palonosetrone 0.25 mg gd1, dexamethasone 12 mg gd1, 8 mg gd2-4. The main endpoint was the percentage of patients with complete remission (CRR), the secondary endpoint was no vomiting, complete control (no vomiting, no rescue antiemetic treatment, no mild or more nausea), and no nausea or adverse reactions occurred in 100 patients. Results A total of 127 patients were enrolled from July 2015 to January 2017. 126 patients were assessable. 1. The complete remission rates of MPD, APD and PD were 87.1%, 81.3%, 71.9% respectively in the delayed phase. There was no significant difference between the two groups (P 0.05). For nausea control, the complete remission rate of APD was the highest in the overall phase, 78.1%, followed by PD. The incidence of nausea was 48.4%, 46.9% and 46.9% in MPD group, APD group and PD group, respectively. There was no significant difference (P The complete remission rates were 96.9% vs 93.5% and 81.3% vs 77.4% respectively, with no significant difference (P 0.05). Conclusion Metoclopramide combined with palonosetron and dexamethasone has similar efficacy and safety in HEC compared with the standard triple antiemetic regimen (aspirin, palonosetron and dexamethasone). The efficacy of norsetron triple antiemetic regimen in preventing CINV in HEC was similar to that of tropisetron triple antiemetic regimen.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R730.53
[Abstract]:Background Chemotherapy-induced nausea and vomiting (CINV) is one of the most common side effects of chemotherapy. 5-HT3 receptor antagonists, NK-1 receptor antagonists and dexamethasone are effective drugs for preventing CINV induced by hyperemetic chemotherapy. However, NK-1 receptor antagonist aspirin is relatively expensive and about 25-35% of patients still receive HEC. CINV did not respond effectively to aspirin in the delayed phase (24-120 hours after chemotherapy). Therefore, finding other effective drugs to prevent delayed CINV is an important clinical problem. A recent clinical study conducted by Rolia et al. showed that metoclopramide combined with dexamethasone in the control of delayed vomiting. This study provides new options for delayed CINV, but there are two shortcomings. First, Rolia et al. studied the use of aspirin in the acute phase (0-24 hours after chemotherapy), which may affect the follow-up effect of metoclopramide on delayed CINV. Second, the daily dose of metoclopramide in Rolia and other studies is 80 mg, while the recommended prescription in China is 10-40 mg daily. The surface area of Chinese people is smaller than that of Europeans. Whether the daily dose of metoclopramide 40 mg can effectively control delayed vomiting remains to be confirmed by further clinical studies. The efficacy and safety of two-generation 5-HT3 receptor antagonists in the triple antiemetic regimen for the prevention of CINV in HEC were also explored. The antiemetic regimens of methoxyclopramine 20 mg bid 2-4, palonosetron 0.25 mg gd1, dexamethasone 20 mg bid 2-4, and dexamethasone 20 mg bid 2-4 were aspirin 125 mg gd1, 80 mg D 2-3, palonosetrone 0.25 mg gd1, dexamethasone 12 mg gd1, 8 mg gd2-4. The main endpoint was the percentage of patients with complete remission (CRR), the secondary endpoint was no vomiting, complete control (no vomiting, no rescue antiemetic treatment, no mild or more nausea), and no nausea or adverse reactions occurred in 100 patients. Results A total of 127 patients were enrolled from July 2015 to January 2017. 126 patients were assessable. 1. The complete remission rates of MPD, APD and PD were 87.1%, 81.3%, 71.9% respectively in the delayed phase. There was no significant difference between the two groups (P 0.05). For nausea control, the complete remission rate of APD was the highest in the overall phase, 78.1%, followed by PD. The incidence of nausea was 48.4%, 46.9% and 46.9% in MPD group, APD group and PD group, respectively. There was no significant difference (P The complete remission rates were 96.9% vs 93.5% and 81.3% vs 77.4% respectively, with no significant difference (P 0.05). Conclusion Metoclopramide combined with palonosetron and dexamethasone has similar efficacy and safety in HEC compared with the standard triple antiemetic regimen (aspirin, palonosetron and dexamethasone). The efficacy of norsetron triple antiemetic regimen in preventing CINV in HEC was similar to that of tropisetron triple antiemetic regimen.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R730.53
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 于世英;印季良;秦叔逵;王杰軍;陳元;沈琳;徐建國;謝廣茹;張力;樊e，
本文編號：2198040
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