177Lu-EB-PSMA Radioligand Therapy with Escalating Doses in Patients with Metastatic Castration-Resistant Prostate Cancer

This study was designed to assess the safety and therapeutic response to 177Lu-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 = 10) was treated with a 1.18 ± 0.09 GBq dose of 177Lu-EB-PSMA. Group B (n = 10) was treated with a 2.12 ± 0.19 GBq dose of 177Lu-EB-PSMA. Group C (n = 8) was treated with a 3.52 ± 0.58 GBq dose of 177Lu-EB-PSMA. Eligible patients received up to 3 cycles of 177Lu-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 prostate-specific 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 = 0.007), but no correlation between groups B and C was found. 68Ga-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 177Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with an increased number of patients are warranted.