177Lu-EB-PSMA radioligand therapy with escalating doses in patients with metastatic castration-resistant prostate cancer.

Purpose: This study is designed to assess the safety and therapeutic response to 177Lu-EB-PSMA treatment with escalating doses in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: With institutional review board approval and informed consent, patients were randomly divided into three groups: Group A (n = 10) were treated with 1.18 ± 0.09 GBq/dose of 177Lu-EB-PSMA. Group B (n = 10) were treated with 2.12 ± 0.19 GBq/dose of 177Lu-EB-PSMA. Group C (n = 8) were treated with 3.52 ± 0.58 GBq/dose of 177Lu-EB-PSMA. Eligible patients received up to three cycles of 177Lu-EB-PSMA therapy, at eight-week intervals. Results: Due to disease progression or bone marrow suppression, 4 out of 10, 5 out of 10, and 5 out of 10 patients completed three cycles therapy as planned in Groups A, B, and C, respectively. The prostate-specific antigen (PSA) response was correlated with treatment dose, with PSA disease control rates in Group B (70%) and C (75%) being higher than that in Group A (10%) (P = 0.007), but no correlation between Group B and Group C was found. 68Ga-PSMA PET/CT showed response in all the treatment groups, however, there was no significant difference between the three groups. Hematologic toxicity study found that platelets in Group B and Group C decreased more than those 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 demonstrates that 2.12 GBq/dose of 177Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with increased number of patients are warranted.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020 May 01 [Epub ahead of print]

Jie Zang, Qingxing Liu, Huimin Sui, Rongxi Wang, Orit Jacobson, Xinrong Fan, Zhaohui Zhu, Xiaoyuan Chen

Peking Union Medical College Hospital, China., Peking Union Medical University Hospital, China., National Institutes of Health, United States.