Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: A randomized, phase II, placebo-controlled trial
Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: A randomized, phase II, placebo-controlled trial
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DOI：
10.1200/jco.2003.04.176
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发表时间：
2003-02-15
影响因子：
45.3
通讯作者：
Nelson, JB
中科院分区：
文献类型：
--
作者：
Carducci, MA;Padley, RJ;Nelson, JB
目的：评价内皮素-A受体拮抗剂阿特拉森坦(ABT-627)治疗激素非依赖性前列腺癌(HRPCa)的有效性和安全性。288名患有HRPCA且有转移疾病证据的无旋风患者被随机分配到三个研究组之一，分别接受每天一次的安慰剂、2.5毫克阿特拉森坦或10毫克阿特拉森坦。主要终点是进展时间；次要终点包括前列腺特异性抗原(PSA)进展时间、骨扫描改变以及骨和肿瘤标志物的改变。结果：三个治疗组在所有基线特征上都相似。意向治疗(ITT)患者(n=288)与安慰剂组相比，10毫克阿特拉森坦组的中位进展时间较长：分别为183天和137天；(P=.13)。可评估患者(n=244)的平均进展时间显著延长，从129天(安慰剂组)延长至196天(10毫克阿特拉森坦组；P=.021)。对于10毫克阿特拉森坦组的ITT和可评估人群，PSA进展的中位时间是安慰剂组的两倍(155比71天；P=.002)。服用安慰剂的患者血清乳酸脱氢酶(LDH)水平继续显著高于基线水平，乳酸脱氢酶[LDH]是疾病负担的标志；在ITT人群中，LDH水平的升高被阿特拉森坦均匀地减弱。头痛、外周水肿和鼻炎是主要的副作用，典型的轻微到中度严重。阿特拉森坦对生活质量无不良影响。结论：阿特拉森坦是一种口服靶向治疗，耐受性良好，有可能延缓HRPCa的进展。(C)2003年，由美国临床肿瘤学会提供。
Purpose : To evaluate the efficacy and safety of atrasentan (ABT-627), an endothelin-A receptor antagonist, in the treatment of asymptornatic, hormone-refractory prostatic adenocarcinoma.Patients and Methods: A double-blind, randomized, placebo-controlled clinical trial of hormone-refractory prostate cancer (HRPCa) patients was conducted in the United States and Europe. Two hundred eighty-eight asymptornatic patients with HRPCa and evidence of metastatic disease were randomly assigned to one of three study groups receiving a once-daily oral dose of placebo, 2.5 mg atrasentan, or 10 mg atrasentan, respectively. Primary end point was time to progression; secondary end points included time to prostate-specific antigen (PSA) progression, bone scan changes, and changes in bone and tumor markers.Results: The three treatment groups were similar in all baseline characteristics. Median time to progression in intent-to-treat (ITT) patients (n = 288) was longer in the 10-mg atrasentan group compared with the placebo group: 183 v 137 days, respectively; (P = .13). Median time to progression in evaluable patients (n = 244) was significantly prolonged, from 129 days (placebo group) to 196 days (10-mg atrasentan group; P = .021). For both ITT and evaluable populations in the 10-mg atrasentan group, median time to PSA progression was twice that of the placebo group (155 v 71 days; P = .002). Patients who received placebo continued to have significant increases from baseline in serum (lactate dehydrogenase [LDH]), a marker of disease burden; elevations in LDH were uniformly attenuated by atrasentan in the ITT population. Headache, peripheral edema, and rhinitis were primary side effects, typically of mild to moderate severity. Quality of life was not adversely affected by atrasentan.Conclusion: Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa. (C) 2003 by American Society of Clinical Oncology.