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

Abstract

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.

• Authors: Jie Zang, Qingxing Liu, Huimin Sui, Rongxi Wang, Orit Jacobson, Xinrong Fan, Zhaohui Zhu, Xiaoyuan Chen
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 61 Issue 12 Pg. 1772-1778 (12 2020) ISSN: 1535-5667 [Electronic] United States
• PMID: 32358086 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the Society of Nuclear Medicine and Molecular Imaging.

Chemical References

• 177Lu-EB-PSMA-617
• Dipeptides
• Heterocyclic Compounds, 1-Ring
• Ligands
• Evans Blue
• Lutetium
• Prostate-Specific Antigen

Topics

• Aged
• Dipeptides (adverse effects, therapeutic use)
• Evans Blue
• Heterocyclic Compounds, 1-Ring (adverse effects, therapeutic use)
• Humans
• Ligands
• Lutetium
• Male
• Neoplasm Metastasis
• Prostate-Specific Antigen
• Prostatic Neoplasms, Castration-Resistant (pathology, radiotherapy)
• Radiation Dosage
• Radiotherapy Dosage
• Safety
• Treatment Outcome