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Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer

BACKGROUND: Radioligand therapy (RLT) with (177)lutetium (Lu)-labelled prostate-specific membrane antigen (PSMA) ligands has been increasingly used in recent years for therapy of metastatic castrate-resistant prostate cancer (mCRPC). Studies have revealed that (177)Lu-PSMA ligand therapy is well tol...

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Autores principales: Gallyamov, Marat, Meyrick, Danielle, Barley, Jerome, Lenzo, Nat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769531/
https://www.ncbi.nlm.nih.gov/pubmed/33391748
http://dx.doi.org/10.1093/ckj/sfz101
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author Gallyamov, Marat
Meyrick, Danielle
Barley, Jerome
Lenzo, Nat
author_facet Gallyamov, Marat
Meyrick, Danielle
Barley, Jerome
Lenzo, Nat
author_sort Gallyamov, Marat
collection PubMed
description BACKGROUND: Radioligand therapy (RLT) with (177)lutetium (Lu)-labelled prostate-specific membrane antigen (PSMA) ligands has been increasingly used in recent years for therapy of metastatic castrate-resistant prostate cancer (mCRPC). Studies have revealed that (177)Lu-PSMA ligand therapy is well tolerated and appears to cause fewer adverse effects than current standard of care third-line treatments. Notably, since (177)Lu-PSMA agents are predominantly excreted by kidneys, there are concerns relating to their potential nephrotoxicity and renal outcomes. Although many recent studies have focused on mostly nephrotoxic adverse reactions at up to 3-month follow-up, assessment of renal outcomes after (177)Lu-PSMA RLT in longer term follow-up is lacking. The aim of this study was to assess the influence of (177)Lu-PSMA RLT on renal function in patients treated for mCRPC at >3 months post-therapy. METHODS: In this retrospective cohort study, we assessed 195 men with progressive mCRPC who had received therapy with (177)Lu-PSMA as second- or third-line after standard therapeutic interventions. Patients underwent investigations with (68)Ga-PSMA-ligand positron emission tomography/computed tomography scan to confirm PSMA-expressing mCRPC. Eligible patients were required to have estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2), an Eastern Cooperative Oncology Group performance status score <3, no severe liver injury (as characterized by liver function tests) and no significant bone marrow dysfunction. Enrolled patients received two to five cycles of intravenous (177)Lu-PSMA I&T or (177)Lu-PSMA-617, at 6- to 10-week intervals. Renal outcomes were assessed according to Kidney Disease: Improving Global Outcomes guidelines as incidence of acute kidney injury (AKI), acute kidney disease (AKD) or chronic kidney disease (CKD). All assessments and tests were undertaken between therapy cycles and at follow-up of at least 3 months. RESULTS: Of 195 assessed men with mCRPC, 110 patients aged [mean ± SD (range)] 70 ± 8 (53–92) years were recruited into this study with median follow-up of 8 (interquartile range 5–12, minimum 3, maximum 29) months and mean baseline eGFR 81 ± 13 mL/min/1.73 m(2). Pre-existing CKD was identified in 12% of patients. None of the patients experienced an AKI during RLT. Two AKD and three CKD G3a cases were identified. Analysis of possible impact of prior CKD and major risk factors (hypertension, diabetes, history of AKI) on incidence of AKD or CKD demonstrated relative risk 4.2 [95% confidence interval (CI) 1.23–14.29] and 1.91 (95% CI 1.14–3.12), respectively. However, Fisher’s exact test did not reveal statistical significance of the impact of both conditions. CONCLUSIONS: Current Lu-PSMA RLT protocols appear to carry a mild nephrotoxic risk with the rate of about 4.5%. Prior CKD is potentially the most significant risk factor of post-RLT renal dysfunction.
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spelling pubmed-77695312020-12-31 Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer Gallyamov, Marat Meyrick, Danielle Barley, Jerome Lenzo, Nat Clin Kidney J Original Articles BACKGROUND: Radioligand therapy (RLT) with (177)lutetium (Lu)-labelled prostate-specific membrane antigen (PSMA) ligands has been increasingly used in recent years for therapy of metastatic castrate-resistant prostate cancer (mCRPC). Studies have revealed that (177)Lu-PSMA ligand therapy is well tolerated and appears to cause fewer adverse effects than current standard of care third-line treatments. Notably, since (177)Lu-PSMA agents are predominantly excreted by kidneys, there are concerns relating to their potential nephrotoxicity and renal outcomes. Although many recent studies have focused on mostly nephrotoxic adverse reactions at up to 3-month follow-up, assessment of renal outcomes after (177)Lu-PSMA RLT in longer term follow-up is lacking. The aim of this study was to assess the influence of (177)Lu-PSMA RLT on renal function in patients treated for mCRPC at >3 months post-therapy. METHODS: In this retrospective cohort study, we assessed 195 men with progressive mCRPC who had received therapy with (177)Lu-PSMA as second- or third-line after standard therapeutic interventions. Patients underwent investigations with (68)Ga-PSMA-ligand positron emission tomography/computed tomography scan to confirm PSMA-expressing mCRPC. Eligible patients were required to have estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2), an Eastern Cooperative Oncology Group performance status score <3, no severe liver injury (as characterized by liver function tests) and no significant bone marrow dysfunction. Enrolled patients received two to five cycles of intravenous (177)Lu-PSMA I&T or (177)Lu-PSMA-617, at 6- to 10-week intervals. Renal outcomes were assessed according to Kidney Disease: Improving Global Outcomes guidelines as incidence of acute kidney injury (AKI), acute kidney disease (AKD) or chronic kidney disease (CKD). All assessments and tests were undertaken between therapy cycles and at follow-up of at least 3 months. RESULTS: Of 195 assessed men with mCRPC, 110 patients aged [mean ± SD (range)] 70 ± 8 (53–92) years were recruited into this study with median follow-up of 8 (interquartile range 5–12, minimum 3, maximum 29) months and mean baseline eGFR 81 ± 13 mL/min/1.73 m(2). Pre-existing CKD was identified in 12% of patients. None of the patients experienced an AKI during RLT. Two AKD and three CKD G3a cases were identified. Analysis of possible impact of prior CKD and major risk factors (hypertension, diabetes, history of AKI) on incidence of AKD or CKD demonstrated relative risk 4.2 [95% confidence interval (CI) 1.23–14.29] and 1.91 (95% CI 1.14–3.12), respectively. However, Fisher’s exact test did not reveal statistical significance of the impact of both conditions. CONCLUSIONS: Current Lu-PSMA RLT protocols appear to carry a mild nephrotoxic risk with the rate of about 4.5%. Prior CKD is potentially the most significant risk factor of post-RLT renal dysfunction. Oxford University Press 2019-08-14 /pmc/articles/PMC7769531/ /pubmed/33391748 http://dx.doi.org/10.1093/ckj/sfz101 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Gallyamov, Marat
Meyrick, Danielle
Barley, Jerome
Lenzo, Nat
Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
title Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
title_full Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
title_fullStr Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
title_full_unstemmed Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
title_short Renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
title_sort renal outcomes of radioligand therapy: experience of (177)lutetium—prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769531/
https://www.ncbi.nlm.nih.gov/pubmed/33391748
http://dx.doi.org/10.1093/ckj/sfz101
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