Details

Autor(en) / Beteiligte

• Zhang, Jingjing
• Kulkarni, Harshad
• Singh, Aviral
• Schuchardt, Christiane
• Niepsch, Karin
• Langbein, Thomas
• Baum, Richard

Titel

177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer patients with a single functioning kidney

Ist Teil von

• The Journal of nuclear medicine (1978), 2019-11, Vol.60 (11), p.1579

Ort / Verlag

New York: Society of Nuclear Medicine

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Objectives: The aim of this study was to assess the safety, tolerability and effects on renal function as well as the therapeutic efficacy of prostate-specific membrane antigen (PSMA) targeted radioligand therapy (PRLT) using lutetium-177 (177Lu) labeled PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) and a single functioning kidney before PRLT. Methods: Sixteen patients (age 53-78 y, mean age 64.7 ± 6.5 y) with a single functioning kidney received PRLT with 177Lu-PSMA-617 between March 2015 and October 2018. All parameters of renal function (serum creatinine, blood urea nitrogen and electrolytes) were prospectively documented in a structured database and analyzed prior to each PRLT cycle and in follow-up. Renal function was further quantified by measuring TER using 99mTc-MAG3 renal scintigraphy. Treatment-related adverse events (AEs) were graded according to the CTCAE v.5.0. Kaplan-Meier analysis was performed to obtain the progression-free survival and overall survival, defined from start of PRLT. Results: A total of 54 cycles of PRLT were performed. The median dosage was 22.1 GBq (range 15.4-33.8 GBq) in 2-6 cycles. Calculated radiation-absorbed doses of kidney per cycle were 5.3 ± 2.1 Gy (0.81±0.32 Gy/GBq). Renal function was already impaired at baseline in 43.7 % patients, according to CTCAE G1 in 25.0% and G2 in 18.8%. G1 and G2 renal functional impairment, respectively, were present in 37.5% and 6.3% of the patients after the first PRLT cycle and in 31.3 % and 12.5% after the second cycle. No G3 or 4 nephrotoxicity was observed during or after treatment. Tubular extraction rate (TER) changed from 135.6 ± 47.3 at baseline to 127.1 ± 41.5 ml/min at follow-up post PRLT, with 10/16 (62.5%) patients showing a fall in renal function (5/16 >10%). The ratio of TER to lower limit TER (TER/TERLoLi) changed from 0.82 ± 0.30 to 0.78 ± 0.29, declining in 10/16 (62.5%) and by more than 10% in 4 (25%) of the patients. However, renal function (both TER as well as TER/TERLoLi ratio) improved in 6/16 (37.5%) patients after treatment. There was no significant change in both TER and TER/TERLoLi ratio after the last cycle of treatment (p>0.05). Any PSA decline 2 months after the first cycle was noted in 9 patients (56.3%) with 7 patients (43.8%) demonstrating a PSA decline of ≥50%. Based on EORTC, disease control rate (DCR) at 2 months (2.1 ± 0.3 months) post-PRLT was 68.8%, encompassing PR in 43.8% and SD in 25.0%, and by RECIST, PR in 43.8%, and SD in 31.3%. The median PFS was 8.1 months based on both EORTC and RECIST. The median overall survival has yet to be reached with a median follow-up time of 19.3 months (range 5.8-45.3 months). Conclusion: In patients with a single functioning kidney, 177Lu-PSMA-617 radioligand therapy is feasible, effective and is very well tolerated without any signs of acute or subacute nephrotoxicity during a mean follow up of nearly 2 years (and up to 45.3 months). Further long-term follow-up of this special patient group is warranted.