福沙匹坦預防高致吐風險化療所致惡心嘔吐的臨床研究
發(fā)布時間：2018-08-25 18:40
【摘要】：目的以阿瑞匹坦膠囊作為陽性對照藥,評價福沙匹坦預防國人重度致吐性抗腫瘤化療引起的惡心和嘔吐的有效性和安全性。方法645例患者以1:1的比例隨機進入試驗組(福沙匹坦組)和對照組(阿瑞匹坦組)�；颊呓邮芨窭经偤偷厝姿陕�(lián)合單一劑量的福沙匹坦(或模擬劑)(150mgd1)或聯(lián)合阿瑞匹坦(或模擬劑)的標準治療(125mgd1;80mgd2-3)。主要療效觀察指標是化療后總觀察期(0～120h,overall phase,OP)內(nèi)嘔吐獲得完全有效的患者比例(嘔吐完全有效率,CRR)。次要療效觀察指標包括急性期(0～24h)嘔吐的CRR;延遲期(25～120h)嘔吐的CRR;化療開始至第1次嘔吐發(fā)作的時間(h)及嘔吐發(fā)作程度(次/日);化療開始至第1次解救治療的時間(h)及解救治療的患者比例;無明顯惡心患者的比例(VAS25mm)及無惡心患者的比例(VAS5mm);體力狀況(ECOGPS評分)變化情況;患者對惡心嘔吐治療的總體滿意度。主要療效終點采用非劣效的模型評價,劣界值是10%。采用CMH卡方檢驗比較兩組之間達CRR的患者比例差異。結(jié)果645例患者進入全集分析(FAS),626例患者進入符合方案集人群分析(PPS)。FAS中,化療后總觀察期內(nèi)福沙匹坦組嘔吐CRR為89.33%,阿瑞匹坦組CRR為92.74%,組間差異無統(tǒng)計學意義(P=0.1330)。兩組在急性期內(nèi)的嘔吐CRR分別為95.73%和95.90%,組間比較差別無統(tǒng)計學意義(P=1.0000)。兩組在延遲期嘔吐CRR分別為91.16%和93.38%,差別無統(tǒng)計學意義(P=0.3065)。PPS結(jié)果與FAS結(jié)果分析一致。FAS中,兩組的嘔吐發(fā)生率分別為9.76%和7.26%,兩組間差別無統(tǒng)計學意義(P=0.2634);兩組的嘔吐控制時間均數(shù)分別為94.07小時和112.23小時,兩組間差別無統(tǒng)計學意義(P=0.2647);兩組的解救時間均數(shù)分別為92.73小時和104.02小時,試驗組的解救時間短于對照組,兩組間差別有統(tǒng)計學意義(P=0.0458);兩組解救治療發(fā)生率分別為6.40%和2.84%,兩組間差別有統(tǒng)計學意義(P=0.0389)。化療后0～24h,25～120h,0～120h各時間段,兩組的嘔吐完全控制率的差別均無統(tǒng)計學意義(P0.05);兩組患者用藥后的第1天至第5天,各天惡心程度控制的有效率和控制率(無明顯惡心的患者比例及無惡心的患者比例)的組間差別均無統(tǒng)計學意義(P0.05)。兩組患者用藥后的第1-5天體力狀況(ECOGPS評分)的差別均無統(tǒng)計學意義(P0.05)�；熀蟮牡�1-5天,兩組患者對惡心嘔吐的總體滿意度(VAS評分)的差別無統(tǒng)計學意義(P0.05)。PPS和FAS結(jié)果分析一致。無論化療方案中是否含順鉑,OP期內(nèi)福沙匹坦的CRR均不劣于阿瑞匹坦。兩組不良事件均可耐受,最常見的不良事件為便秘。結(jié)論福沙匹坦能夠有效預防國人重度致吐性抗腫瘤化療引起的惡心和嘔吐,并且安全性好。福沙匹坦提供了一種預防化療引起的惡心和嘔吐的新選擇。
[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.
【學位授予單位】：南京醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R730.53
本文編號：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.
【學位授予單位】：南京醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R730.53
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