Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer
Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer
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DOI：
10.1200/jco.2004.09.154
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发表时间：
2004-07-01
影响因子：
45.3
通讯作者：
Bander, NH
中科院分区：
文献类型：
--
作者：
Milowsky, MI;Nanus, DM;Bander, NH
目的确定最大耐受剂量（MTD）、毒性、人抗人抗体（HAHA）反应、药代动力学、器官剂量学、靶向性、钇-90标记抗前列腺特异性膜抗原单克隆抗体J591的初步疗效在雄激素非依赖性前列腺癌（PC）患者中，使用Y-90-J591进行治疗。独立PC和疾病进展证据接受铟-111-J591进行药代动力学和生物分布测定，1周后接受5个剂量水平的90 Y-J591：5、10、15、17.5和20 mCi/m2。如果血小板和中性粒细胞的恢复是令人满意的。结果29例雄激素非依赖性PC患者接受Y-90-J591，其中4人重新治疗。剂量限制性毒性（DLT）在20 mCi/m2时出现，2名患者出现血小板减少症，伴非危及生命的出血事件，需要输注血小板。17.5 mCi/m2剂量水平被确定为MTD。没有重新治疗的患者发生DLT。非血液学毒性不是剂量限制性的。在大多数患者中观察到已知骨和软组织转移部位的靶向。未观察到HAHA反应。观察到抗肿瘤活性，2例患者在恢复至基线前，前列腺特异性抗原（PSA）水平分别下降85%和70%，持续8个月和8.6个月。两例患者均具有客观可测量的疾病缓解。结论Y-90-J591的推荐剂量为17.5mCi/m2。可接受的毒性、对已知PC转移部位的良好靶向作用以及在雄激素非依赖性PC患者中的生物学活性证明了Y-90-J591治疗PC患者的进一步研究。(C)2004年，美国临床肿瘤学会。
Purpose To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (Y-90-J591) in patients with androgen-independent prostate cancer (PC).Patients and Methods Patients with androgen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by 90Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m(2). Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory.Results Twenty-nine patients with androgen-independent PC received Y-90-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m(2), with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m(2) dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization.Conclusion The recommended dose for Y-90-J591 is 17.5 mCi/m(2). Acceptable toxicity, excellent targeting of known of sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of Y-90-J591 in the treatment of patients with PC. (C) 2004 by American Society of Clinical Oncology.