福沙匹坦预防高致吐风险化疗所致恶心呕吐的临床研究
发布时间：2018-08-25 18:40
【摘要】：目的以阿瑞匹坦胶囊作为阳性对照药,评价福沙匹坦预防国人重度致吐性抗肿瘤化疗引起的恶心和呕吐的有效性和安全性。方法645例患者以1:1的比例随机进入试验组(福沙匹坦组)和对照组(阿瑞匹坦组)。患者接受格拉司琼和地塞米松联合单一剂量的福沙匹坦(或模拟剂)(150mgd1)或联合阿瑞匹坦(或模拟剂)的标准治疗(125mgd1;80mgd2-3)。主要疗效观察指标是化疗后总观察期(0～120h,overall phase,OP)内呕吐获得完全有效的患者比例(呕吐完全有效率,CRR)。次要疗效观察指标包括急性期(0～24h)呕吐的CRR;延迟期(25～120h)呕吐的CRR;化疗开始至第1次呕吐发作的时间(h)及呕吐发作程度(次/日);化疗开始至第1次解救治疗的时间(h)及解救治疗的患者比例;无明显恶心患者的比例(VAS25mm)及无恶心患者的比例(VAS5mm);体力状况(ECOGPS评分)变化情况;患者对恶心呕吐治疗的总体满意度。主要疗效终点采用非劣效的模型评价,劣界值是10%。采用CMH卡方检验比较两组之间达CRR的患者比例差异。结果645例患者进入全集分析(FAS),626例患者进入符合方案集人群分析(PPS)。FAS中,化疗后总观察期内福沙匹坦组呕吐CRR为89.33%,阿瑞匹坦组CRR为92.74%,组间差异无统计学意义(P=0.1330)。两组在急性期内的呕吐CRR分别为95.73%和95.90%,组间比较差别无统计学意义(P=1.0000)。两组在延迟期呕吐CRR分别为91.16%和93.38%,差别无统计学意义(P=0.3065)。PPS结果与FAS结果分析一致。FAS中,两组的呕吐发生率分别为9.76%和7.26%,两组间差别无统计学意义(P=0.2634);两组的呕吐控制时间均数分别为94.07小时和112.23小时,两组间差别无统计学意义(P=0.2647);两组的解救时间均数分别为92.73小时和104.02小时,试验组的解救时间短于对照组,两组间差别有统计学意义(P=0.0458);两组解救治疗发生率分别为6.40%和2.84%,两组间差别有统计学意义(P=0.0389)。化疗后0～24h,25～120h,0～120h各时间段,两组的呕吐完全控制率的差别均无统计学意义(P0.05);两组患者用药后的第1天至第5天,各天恶心程度控制的有效率和控制率(无明显恶心的患者比例及无恶心的患者比例)的组间差别均无统计学意义(P0.05)。两组患者用药后的第1-5天体力状况(ECOGPS评分)的差别均无统计学意义(P0.05)。化疗后的第1-5天,两组患者对恶心呕吐的总体满意度(VAS评分)的差别无统计学意义(P0.05)。PPS和FAS结果分析一致。无论化疗方案中是否含顺铂,OP期内福沙匹坦的CRR均不劣于阿瑞匹坦。两组不良事件均可耐受,最常见的不良事件为便秘。结论福沙匹坦能够有效预防国人重度致吐性抗肿瘤化疗引起的恶心和呕吐,并且安全性好。福沙匹坦提供了一种预防化疗引起的恶心和呕吐的新选择。
[Abstract]:Objective to evaluate the efficacy and safety of arapitam capsule in preventing nausea and vomiting induced by severe emetic antitumor chemotherapy in Chinese. Methods 645 patients were randomly enrolled into the trial group (fosapitam group) and the control group (Aripitan group) at 1:1. Patients received standard treatment of granisetron and dexamethasone in combination with a single dose of fosapidam (or analogue) (150mgd1) or a combination of aripitan (or analogue) (125 MGd1 / 80mgd2-3). The main outcome measure was the proportion of patients with complete effective vomiting in the total observation period (0 ~ 120 h) after chemotherapy (complete effective rate of vomiting). The secondary therapeutic indicators included the onset of CRR; chemotherapy from the onset of vomiting to the first time of vomiting and the degree of vomiting attack (times / day) in acute stage (0 ~ 24 h) with CRR; delay (25 ~ 120 h), and from the beginning of chemotherapy to the first time of rescue therapy. The time of (h) and the proportion of patients treated with rescue; The proportion of patients without nausea (VAS25mm) and the proportion of patients without nausea (VAS5mm); the changes of physical condition (ECOGPS score); the overall satisfaction of patients with nausea and vomiting treatment. The main therapeutic endpoints were evaluated by non-inferior model, and the inferior value was 10. CMH chi-square test was used to compare the proportion of patients with CRR between the two groups. Results six hundred and forty-five patients were included in the whole set analysis of (FAS). 626 patients entered the consistent set analysis of (PPS). The total observation period after chemotherapy was that the CRR in the fosapitam group was 89.33 and the CRR in the Aripitan group was 92.74. There was no significant difference between the two groups (P < 0.1330). The CRR of vomiting in the two groups was 95.73% and 95.90%, respectively, and there was no significant difference between the two groups (P = 1.0000). The difference of CRR between the two groups in delayed vomiting was 91.16% and 93.38%, respectively. There was no significant difference between the two groups (P0. 3065). The results of PPS were consistent with those of FAS. The incidence of vomiting in the two groups was 9.76% and 7.26%, respectively, and there was no significant difference between the two groups (P < 0.2634), the mean control time of vomiting in the two groups was 94.07 hours and 112.23 hours, respectively. There was no significant difference between the two groups (P0. 2647), the mean rescue time of the two groups was 92.73 hours and 104.02 hours, respectively. The rescue time of the experimental group was shorter than that of the control group. The difference between the two groups was statistically significant (P0. 0458), and the incidence of rescue therapy in the two groups was 6. 40% and 2. 84%, respectively. The difference between the two groups was statistically significant (P0. 0389). There was no significant difference in the rate of complete control of vomiting between the two groups (P0.05) in each time period of 0 ~ 24h ~ 25h ~ 120h after chemotherapy (P0.05), between the first day and the fifth day after the treatment, there was no significant difference between the two groups in the complete control rate of vomiting (P0.05). There was no significant difference in the effective rate and control rate between groups (no significant nausea and no nausea) between groups (P0.05). There was no significant difference in physical status (ECOGPS score) between the two groups on day 1-5 (P0.05). On the 1-5 days after chemotherapy, there was no significant difference in total satisfaction (VAS score) between the two groups (P0.05). The results of PPS and FAS were consistent. No matter whether the chemotherapy regimen contained cisplatin or not, the CRR of fosacitam in op phase was not inferior to that of aripitan. Two groups of adverse events can be tolerated, the most common adverse events are constipation. Conclusion Forssapitam can effectively prevent nausea and vomiting caused by severe emetic anti-tumor chemotherapy in Chinese and is safe. Fosapitam offers a new option to prevent nausea and vomiting caused by chemotherapy.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R730.53
本文编号：2203760
[Abstract]:Objective to evaluate the efficacy and safety of arapitam capsule in preventing nausea and vomiting induced by severe emetic antitumor chemotherapy in Chinese. Methods 645 patients were randomly enrolled into the trial group (fosapitam group) and the control group (Aripitan group) at 1:1. Patients received standard treatment of granisetron and dexamethasone in combination with a single dose of fosapidam (or analogue) (150mgd1) or a combination of aripitan (or analogue) (125 MGd1 / 80mgd2-3). The main outcome measure was the proportion of patients with complete effective vomiting in the total observation period (0 ~ 120 h) after chemotherapy (complete effective rate of vomiting). The secondary therapeutic indicators included the onset of CRR; chemotherapy from the onset of vomiting to the first time of vomiting and the degree of vomiting attack (times / day) in acute stage (0 ~ 24 h) with CRR; delay (25 ~ 120 h), and from the beginning of chemotherapy to the first time of rescue therapy. The time of (h) and the proportion of patients treated with rescue; The proportion of patients without nausea (VAS25mm) and the proportion of patients without nausea (VAS5mm); the changes of physical condition (ECOGPS score); the overall satisfaction of patients with nausea and vomiting treatment. The main therapeutic endpoints were evaluated by non-inferior model, and the inferior value was 10. CMH chi-square test was used to compare the proportion of patients with CRR between the two groups. Results six hundred and forty-five patients were included in the whole set analysis of (FAS). 626 patients entered the consistent set analysis of (PPS). The total observation period after chemotherapy was that the CRR in the fosapitam group was 89.33 and the CRR in the Aripitan group was 92.74. There was no significant difference between the two groups (P < 0.1330). The CRR of vomiting in the two groups was 95.73% and 95.90%, respectively, and there was no significant difference between the two groups (P = 1.0000). The difference of CRR between the two groups in delayed vomiting was 91.16% and 93.38%, respectively. There was no significant difference between the two groups (P0. 3065). The results of PPS were consistent with those of FAS. The incidence of vomiting in the two groups was 9.76% and 7.26%, respectively, and there was no significant difference between the two groups (P < 0.2634), the mean control time of vomiting in the two groups was 94.07 hours and 112.23 hours, respectively. There was no significant difference between the two groups (P0. 2647), the mean rescue time of the two groups was 92.73 hours and 104.02 hours, respectively. The rescue time of the experimental group was shorter than that of the control group. The difference between the two groups was statistically significant (P0. 0458), and the incidence of rescue therapy in the two groups was 6. 40% and 2. 84%, respectively. The difference between the two groups was statistically significant (P0. 0389). There was no significant difference in the rate of complete control of vomiting between the two groups (P0.05) in each time period of 0 ~ 24h ~ 25h ~ 120h after chemotherapy (P0.05), between the first day and the fifth day after the treatment, there was no significant difference between the two groups in the complete control rate of vomiting (P0.05). There was no significant difference in the effective rate and control rate between groups (no significant nausea and no nausea) between groups (P0.05). There was no significant difference in physical status (ECOGPS score) between the two groups on day 1-5 (P0.05). On the 1-5 days after chemotherapy, there was no significant difference in total satisfaction (VAS score) between the two groups (P0.05). The results of PPS and FAS were consistent. No matter whether the chemotherapy regimen contained cisplatin or not, the CRR of fosacitam in op phase was not inferior to that of aripitan. Two groups of adverse events can be tolerated, the most common adverse events are constipation. Conclusion Forssapitam can effectively prevent nausea and vomiting caused by severe emetic anti-tumor chemotherapy in Chinese and is safe. Fosapitam offers a new option to prevent nausea and vomiting caused by chemotherapy.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R730.53
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