比较甲氧氯普胺与阿瑞匹坦预防延迟性化疗致恶心呕吐的临床研究
发布时间：2018-08-22 19:10
【摘要】：研究背景呕吐(Chemotherapy-induced nausea and vomiting,CINV)是化疗中最常见的副反应之一,5-HT3受体拮抗剂、NK-1受体拮抗剂及地塞米松是预防高致吐性化疗所致CINV的有效药物。但NK-1受体拮抗剂阿瑞匹坦价格相对较高,且仍有约25～35%接受HEC的患者使用阿瑞匹坦后在延迟期(化疗后24～120小时)CINV未能得到有效缓解。因此,寻找其他有效药物来预防延迟性CINV是目前临床面临的重要问题。近期Rolia等进行的一项临床研究结果显示,在控制延迟期呕吐中甲氧氯普胺联合地塞米松所产生的疗效并不劣于阿瑞匹坦联合地塞米松(完全缓解率82.5%vs 80.3%,P0.05)。该研究给延迟性CINV带来了新的选择,但存在以下两点不足:一、Rolia等研究在急性期(化疗后0～24h)均使用了阿瑞匹坦,可能影响后续甲氧氯普胺对延迟期CINV的作用;二、在Rolia等研究中甲氧氯普胺的日剂量是80mg,而我国止吐指南推荐用法是每日10～40mg。中国人体表面积较欧洲人小,甲氧氯普胺日剂量40mg能否有效控制延迟期呕吐有待进一步临床研究证实。研究目的比较甲氧氯普胺与阿瑞匹坦在联合地塞米松基础上预防HEC引起的延迟性恶心呕吐的疗效和安全性。同时也探索在三联止吐方案中,两代5-HT3受体拮抗剂对预防HEC中CINV的疗效和安全性。研究方法将在接受HEC治疗的恶性实体瘤患者,随机分配到四个止吐方案组,MPD组的止吐方案为甲氧氯普胺20mgbidd2～4;帕洛诺司琼0.25mgd1;地塞米松20mgd1,8mgbidd2～4。APD组的止吐方案为阿瑞匹坦125mgd1,80mg d2～3;帕洛诺司琼0.25mgd1;地塞米松12mgd1,8mgd2～4。ATD组的止吐方案为阿瑞匹坦125mgd1,80mgd2～3;托烷司琼5mgd1;地塞米松12mg d1,8mg d2～4。PD组的止吐方案为帕洛诺司琼0.25mg d1;地塞米松12mg d1,8mg d2～4。主要研究终点是完全缓解的患者百分比(CRR),次要研究终点是无呕吐、完全控制(无呕吐及无解救性止吐治疗、无轻度以上恶心)、无恶心及不良反应发生的患者百分比。研究结果从2015年7月至2017年1月,一共纳入127名患者,其中126名患者可评估。1、MPD组、APD组及PD组在延迟期获得的完全缓解率分别为87.1%、81.3%、71.9%,差异无统计学意义(P0.05)。对于恶心的控制,APD组在总体期的完全控制率最高,为78.1%,其次为MPD组(74.2%),最后为PD组(68.8%)。无恶心的发生率在MPD组、APD组及PD组分别为48.4%、46.9%及46.9%,差异无统计学意义(P0.05)。2、APD组与ATD组在总体期获得的完全缓解率分别为81.3%、77.4%,差异无统计学意义(P =0.707)。而在急性期和延迟期APD组与ATD组获得的完全缓解率分别为96.9%vs 93.5%、81.3%vs 77.4%,差异均无统计学意义(P0.05)。对于恶心的控制,APD组与ATD组在总体期的完全控制率和无恶心率分别为 78.1%vs 74.2%(P0.05)、46.9%vs 41.9%(P0.05)。3、四组主要不良反应为便秘、乏力及呃逆,不良反应发生率无统计学意义(P0.05),患者均可以耐受。研究结论甲氧氯普胺联合帕洛诺司琼及地塞米松的止吐方案,与标准的三联止吐方案(阿瑞匹坦、帕洛诺司琼及地塞米松)相比,两组止吐方案在HEC中具有相似的疗效及安全性。同时,还发现含帕洛诺司琼的三联止吐方案在预防HEC中CINV的疗效与含托烷司琼的三联止吐方案相似。
[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.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：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.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730.53
【参考文献】
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1 于世英;印季良;秦叔逵;王杰军;陈元;沈琳;徐建国;谢广茹;张力;樊e，
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