镥-177 标记的抗前列腺特异性膜抗原单克隆抗体 J591 治疗转移性去势抵抗性前列腺癌的 II 期研究。
Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer.
机构信息
Authors' Affiliations: Weill Cornell Medical College (WCMC); Weill Cornell Cancer Center; Memorial Sloan-Kettering Cancer Center (MSKCC), New York, New York; and University of North Carolina Chapel Hill, North Carolina.
出版信息
Clin Cancer Res. 2013 Sep 15;19(18):5182-91. doi: 10.1158/1078-0432.CCR-13-0231. Epub 2013 May 28.
PURPOSE
To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; (177)Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival.
EXPERIMENTAL DESIGN
In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of (177)Lu-J591 (15 patients at 65 mCi/m(2), 17 at 70 mCi/m(2)) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m(2) to verify response rate and examine biomarkers.
RESULTS
Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received (177)Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m(2)) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond.
CONCLUSION
A single dose of (177)Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising.
目的
通过前列腺特异性抗原（PSA）下降、可测量疾病反应和生存情况，评估单次输注放射性标记的抗前列腺特异性膜抗原（PSMA）单克隆抗体 J591（镥-177；177Lu）的疗效。
实验设计
在这项双中心 II 期研究中，两个转移性去势抵抗性前列腺癌进展的队列患者接受了单次（177）Lu-J591 治疗（15 例患者为 65mCi/m2，17 例为 70mCi/m2），并进行了放射性核素成像。扩展队列（n=15）接受 70mCi/m2 剂量以验证缓解率并检查生物标志物。
结果
47 例在激素治疗后进展的患者（55.3%还接受了先前的化疗）接受了（177）Lu-J591 治疗。共有 10.6%的患者 PSA 下降≥50%，36.2%的患者 PSA 下降≥30%，59.6%的患者 PSA 有任何下降。12 例可测量疾病中有 1 例出现部分影像学缓解（8 例疾病稳定）。通过平面成像确定 47 例患者中有 44 例（93.6%）的前列腺癌转移灶为目标。所有患者均经历了可逆性血液学毒性，其中 46.8%（29.8%接受血小板输注）发生 4 级血小板减少症，无明显出血。共有 25.5%的患者发生 4 级中性粒细胞减少症，1 例发生发热性中性粒细胞减少症。I 期最大耐受剂量（70mCi/m2）导致更多的 PSA 下降（46.9% vs. 13.3%，P=0.048）和更长的生存时间（21.8 个月 vs. 11.9 个月，P=0.03），但也导致更严重的 4 级血液学毒性和血小板输注。未发生严重的非血液学毒性。那些 PSMA 成像较差的患者不太可能有反应。
结论
单次给予（177）Lu-J591 耐受性良好，具有可逆性骨髓抑制。通过影像学证据证明了准确的肿瘤靶向和 PSA 反应与剂量反应有关。成像生物标志物似乎很有前景。
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