目的评价信迪利单抗对比安慰剂联合化疗(顺铂加紫杉醇或顺铂加5-氟尿嘧啶)作为不可切除的局部晚期、复发或转移性食管鳞癌一线治疗的效果。设计多中心、随机、双盲、Ⅲ期临床研究。背景2018年12月14日至2021年4月9日,国内66家研究中心,...目的评价信迪利单抗对比安慰剂联合化疗(顺铂加紫杉醇或顺铂加5-氟尿嘧啶)作为不可切除的局部晚期、复发或转移性食管鳞癌一线治疗的效果。设计多中心、随机、双盲、Ⅲ期临床研究。背景2018年12月14日至2021年4月9日,国内66家研究中心,国外13家研究中心。受试者659例未曾接受过系统性治疗的成年(≥18岁)晚期或转移性食管鳞癌患者。干预受试者按1∶1的比例随机分组,每3周接受1次信迪利单抗或安慰剂(体重<60 kg者3 mg/kg,体重>60 kg者200 mg)与顺铂75 mg/m2和紫杉醇175 mg/m2的联合治疗。本研究经修订,允许研究者选择顺铂联合紫杉醇或顺铂联合5-氟尿嘧啶(800 mg/m2,第1~5天连续输注给药)化疗方案。主要结局指标所有患者和程序性细胞死亡配体1(PD-L1)表达联合阳性评分≥10的患者总生存期。结果659例患者随机分配至信迪利单抗(n=327)或安慰剂(n=332)联合化疗组。659例患者中有616例(93%)接受了信迪利单抗或安慰剂与顺铂和紫杉醇联合治疗,有43例(7%)接受了信迪利单抗或安慰剂与顺铂和5-氟尿嘧啶联合治疗。期中分析显示,在所有患者(中位总生存期16.7 vs 12.5个月,风险比0.63,95%可信区间0.51~0.78;P<0.001)和联合阳性评分≥10的患者(17.2 vs 13.6个月,0.64,0.48~0.85;P=0.002)中,信迪利单抗联合化疗组的总生存期均优于安慰剂联合化疗组。与安慰剂联合化疗相比,信迪利单抗联合化疗显著延长了所有患者(7.2 vs 5.7个月,0.56,0.46~0.68;P<0.001)和联合阳性评分≥10患者(8.3 vs 6.4个月,0.58,0.45~0.75;P<0.001)的无进展生存期。信迪利单抗联合化疗组出现治疗相关不良事件的患者人数为321/327例(98%),安慰剂联合化疗组为326/332例(98%)。在信迪利单抗联合化疗组和安慰剂联合化疗组中,3级及以上治疗相关不良事件的发生率分别为60%(196/327)和55%(181/332)。结论与安慰剂相比,信迪利单抗联合顺铂加紫杉醇作为一�展开更多
BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality.Among patients who undergo computed tomograph y (CT) within three hours after the onset of intracerebral...BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality.Among patients who undergo computed tomograph y (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can red uce hematoma growth after intracerebral hemorrhage. METHODS: We randomly assigne d 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 μg of rFVIIa per kilogram of body weight (108 patients), 80 μg per kilogram (92 patients), or 160 μg per k ilogram (103 patients) within one hour after the baseline scan. The primary outc ome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Hematoma volu me increased more in the placebo group than in the rFVIIa groups. The mean incre ase was 29 percent in the placebo group, as compared with 16 percent, 14 percent , and 11 percent in the groups given 40 μg, 80 μg, and 160 μg of rFVIIa per k ilogram, respectively (P=0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduce d by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine percent of placebo-treated pati ents died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the pati ents who were given 40, 80, and 160 μg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 perce nt in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral i展开更多
文摘目的评价信迪利单抗对比安慰剂联合化疗(顺铂加紫杉醇或顺铂加5-氟尿嘧啶)作为不可切除的局部晚期、复发或转移性食管鳞癌一线治疗的效果。设计多中心、随机、双盲、Ⅲ期临床研究。背景2018年12月14日至2021年4月9日,国内66家研究中心,国外13家研究中心。受试者659例未曾接受过系统性治疗的成年(≥18岁)晚期或转移性食管鳞癌患者。干预受试者按1∶1的比例随机分组,每3周接受1次信迪利单抗或安慰剂(体重<60 kg者3 mg/kg,体重>60 kg者200 mg)与顺铂75 mg/m2和紫杉醇175 mg/m2的联合治疗。本研究经修订,允许研究者选择顺铂联合紫杉醇或顺铂联合5-氟尿嘧啶(800 mg/m2,第1~5天连续输注给药)化疗方案。主要结局指标所有患者和程序性细胞死亡配体1(PD-L1)表达联合阳性评分≥10的患者总生存期。结果659例患者随机分配至信迪利单抗(n=327)或安慰剂(n=332)联合化疗组。659例患者中有616例(93%)接受了信迪利单抗或安慰剂与顺铂和紫杉醇联合治疗,有43例(7%)接受了信迪利单抗或安慰剂与顺铂和5-氟尿嘧啶联合治疗。期中分析显示,在所有患者(中位总生存期16.7 vs 12.5个月,风险比0.63,95%可信区间0.51~0.78;P<0.001)和联合阳性评分≥10的患者(17.2 vs 13.6个月,0.64,0.48~0.85;P=0.002)中,信迪利单抗联合化疗组的总生存期均优于安慰剂联合化疗组。与安慰剂联合化疗相比,信迪利单抗联合化疗显著延长了所有患者(7.2 vs 5.7个月,0.56,0.46~0.68;P<0.001)和联合阳性评分≥10患者(8.3 vs 6.4个月,0.58,0.45~0.75;P<0.001)的无进展生存期。信迪利单抗联合化疗组出现治疗相关不良事件的患者人数为321/327例(98%),安慰剂联合化疗组为326/332例(98%)。在信迪利单抗联合化疗组和安慰剂联合化疗组中,3级及以上治疗相关不良事件的发生率分别为60%(196/327)和55%(181/332)。结论与安慰剂相比,信迪利单抗联合顺铂加紫杉醇作为一�
文摘BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality.Among patients who undergo computed tomograph y (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can red uce hematoma growth after intracerebral hemorrhage. METHODS: We randomly assigne d 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 μg of rFVIIa per kilogram of body weight (108 patients), 80 μg per kilogram (92 patients), or 160 μg per k ilogram (103 patients) within one hour after the baseline scan. The primary outc ome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Hematoma volu me increased more in the placebo group than in the rFVIIa groups. The mean incre ase was 29 percent in the placebo group, as compared with 16 percent, 14 percent , and 11 percent in the groups given 40 μg, 80 μg, and 160 μg of rFVIIa per k ilogram, respectively (P=0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduce d by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine percent of placebo-treated pati ents died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the pati ents who were given 40, 80, and 160 μg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 perce nt in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral i
