<sup>177</sup>Lu-EB-PSMA Radioligand Therapy with Escalating Doses in Patients with Metastatic Castration-Resistant Prostate Cancer
Jie Zang, Qingxing Liu, Huimin Sui, Rongxi Wang, Orit Jacobson, Xinrong Fan, Zhaohui Zhu, Xiaoyuan Chen
Abstract
This study was designed to assess the safety and therapeutic response to 177 Lu-labeled Evans blue-modified prostate-specific membrane antigen (PSMA) 617 (EB-PSMA-617) treatment with escalating doses in patients with metastatic castration-resistant prostate cancer. Methods: With institutional review board approval and informed consent, patients were randomly divided into 3 groups: group A (n 5 10) was treated with a 1.18 0.09 GBq dose of 177 Lu-EB-PSMA. Group B (n 5 10) was treated with a 2.12 0.19 GBq dose of 177 Lu-EB-PSMA. Group C (n 5 8) was treated with a 3.52 0.58 GBq dose of 177 Lu-EB-PSMA. Eligible patients received up to 3 cycles of 177 Lu-EB-PSMA therapy, at 8-wk intervals. Results: Because of disease progression or bone marrow suppression, 4 of 10, 5 of 10, and 5 of 8 patients completed 3 cycles of therapy as planned in groups A, B, and C, respectively. The prostatespecific antigen response was correlated with treatment dose, and the prostate-specific antigen disease control rates were higher in groups B (70%) and C (75%) than in group A (10%) (P 5 0.007), but no correlation between groups B and C was found. 68 Ga-PSMA PET/CT showed a response in all treatment groups; however, there was no significant difference among the 3 groups. A hematologic toxicity study found that platelets decreased more in groups B and C than in group A and that grade 4 thrombocytopenia occurred in 2 (25.0%) patients in group C. No serious nephritic or hepatic side effects were observed. Conclusion: This study demonstrated that a 2.12-GBq dose of 177 Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with an increased number of patients are warranted.