Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer
Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer
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DOI：
10.1200/jco.2005.05.160
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发表时间：
2005-07-20
影响因子：
45.3
通讯作者：
Goldsmith, SJ
中科院分区：
文献类型：
--
作者：
Bander, NH;Milowsky, MI;Goldsmith, SJ
目的测定J591的最大耐受剂量（MTD）、毒性、人体抗J591应答、药代动力学（PK）、器官剂量学、靶向性、（177）镥标记抗前列腺特异性膜抗原（PSMA）单克隆抗体J591的生物学活性（Lu-177-J591）在雄激素非依赖性前列腺癌（PC）患者中的应用。独立PC收到了Lu-177-J591。所有患者均接受Lu-177-J591成像、PK和生物分布测定。患者有资格为三个retreatments. ResultsThirteen患者收到Lu-177-J591，其中16人收到了三个剂量。骨髓抑制在75 mCi/m2时是剂量限制性的，70 mCi/m2剂量水平被确定为单次给药MTD。45 - 60 mCi/m2重复给药与剂量限制性骨髓抑制相关;然而，最多3次30 mCi/m2剂量可以安全给药。非血液学毒性，无剂量限制性。在所有30例骨、计算机断层扫描或磁共振图像阳性的患者中，均观察到所有已知的骨和软组织转移部位。无论给药次数如何，没有患者对去免疫J591产生人抗J591抗体应答。观察到4名患者的前列腺特异性抗原（PSA）水平下降>= 50%，持续3+至8个月。另外16名患者（46%）的PSA稳定时间中位数为60天（范围为1至21 +个月）。结论Lu-177-J591的MTD为70 mCi/m（2）]多次给药30 mCi/m（2）耐受性良好。可接受的毒性、对已知PC转移部位的良好靶向作用以及雄激素非依赖性PC患者的生物活性值得进一步研究。
PurposeTo determine the maximum tolerated dose (MTD), toxicity, human anti-J591 response, pharmacokinetics (PK), organ dosimetry, targeting, and biologic activity of (177)Lutetium-labeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (Lu-177-J591) in patients with androgen- independent prostate cancer (PC).Patients and MethodsThirty-five patients with progressing androgen-independent PC received Lu-177-J591. All patients underwent Lu-177-J591 imaging, PK, and biodistribution determinations. Patients were eligible for up to three retreatments.ResultsThirty-five patients received Lu-177-J591, of whom 16 received up to three doses. Myelosuppression was dose limiting at 75 mCi/m(2), and the 70-mCi/m(2) dose level was determined to be the single-dose MTD. Repeat dosing at 45 to 60 mCi/m(2) was associated with dose-limiting myelosuppression; however, up to three doses of 30 mCi/m(2) could be safely administered. Nonhematologic toxicity,was not dose,limiting. Targeting of all known sites of bone and soft tissue metastases was seen in all 30 patients with positive bone, computed tomography, or magnetic resonance images. No patient developed a human anti-J591 antibody response to deimmunized J591 regardless of number of doses. Biologic activity was seen with four patients experiencing >= 50% declines in prostate-specific antigen (PSA) levels lasting from 3+ to 8 months. An additional 16 patients (46%) experienced PSA stabilization for a median of 60 days (range, 1 to 21 + months).ConclusionThe MTD of Lu-177-J591 is 70 mCi/m(2)] Multiple doses of 30 mCi/m(2) are well tolerated. Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation.