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Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T
SIMPLE SUMMARY: Radioligand therapy (RLT) with prostate-specific membrane antigen (PSMA)-directed agents has shown remarkable results in patients with advanced prostate cancer. Our objective was to provide data on the side effect profile of PSMA-directed RLT using the therapeutic radiotracer [(177)L...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833540/ https://www.ncbi.nlm.nih.gov/pubmed/35158913 http://dx.doi.org/10.3390/cancers14030647 |
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author | Hartrampf, Philipp E. Weinzierl, Franz-Xaver Serfling, Sebastian E. Pomper, Martin G. Rowe, Steven P. Higuchi, Takahiro Seitz, Anna Katharina Kübler, Hubert Buck, Andreas K. Werner, Rudolf A. |
author_facet | Hartrampf, Philipp E. Weinzierl, Franz-Xaver Serfling, Sebastian E. Pomper, Martin G. Rowe, Steven P. Higuchi, Takahiro Seitz, Anna Katharina Kübler, Hubert Buck, Andreas K. Werner, Rudolf A. |
author_sort | Hartrampf, Philipp E. |
collection | PubMed |
description | SIMPLE SUMMARY: Radioligand therapy (RLT) with prostate-specific membrane antigen (PSMA)-directed agents has shown remarkable results in patients with advanced prostate cancer. Our objective was to provide data on the side effect profile of PSMA-directed RLT using the therapeutic radiotracer [(177)Lu]Lu-PSMA I&T. We evaluated patients with castration-resistant metastatic prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA I&T. A substantial fraction of the patients already had impaired renal function and/or reduced white blood cell counts at baseline, but the degree of nephrotoxicity or hematotoxicity under RLT was low. No severe toxicities occurred under RLT. ABSTRACT: (1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [(177)Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [(99m)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman’s rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [(177)Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent. |
format | Online Article Text |
id | pubmed-8833540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88335402022-02-12 Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T Hartrampf, Philipp E. Weinzierl, Franz-Xaver Serfling, Sebastian E. Pomper, Martin G. Rowe, Steven P. Higuchi, Takahiro Seitz, Anna Katharina Kübler, Hubert Buck, Andreas K. Werner, Rudolf A. Cancers (Basel) Article SIMPLE SUMMARY: Radioligand therapy (RLT) with prostate-specific membrane antigen (PSMA)-directed agents has shown remarkable results in patients with advanced prostate cancer. Our objective was to provide data on the side effect profile of PSMA-directed RLT using the therapeutic radiotracer [(177)Lu]Lu-PSMA I&T. We evaluated patients with castration-resistant metastatic prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA I&T. A substantial fraction of the patients already had impaired renal function and/or reduced white blood cell counts at baseline, but the degree of nephrotoxicity or hematotoxicity under RLT was low. No severe toxicities occurred under RLT. ABSTRACT: (1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [(177)Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [(99m)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman’s rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [(177)Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent. MDPI 2022-01-27 /pmc/articles/PMC8833540/ /pubmed/35158913 http://dx.doi.org/10.3390/cancers14030647 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hartrampf, Philipp E. Weinzierl, Franz-Xaver Serfling, Sebastian E. Pomper, Martin G. Rowe, Steven P. Higuchi, Takahiro Seitz, Anna Katharina Kübler, Hubert Buck, Andreas K. Werner, Rudolf A. Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T |
title | Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T |
title_full | Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T |
title_fullStr | Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T |
title_full_unstemmed | Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T |
title_short | Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T |
title_sort | hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [(177)lu]lu-psma i&t |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833540/ https://www.ncbi.nlm.nih.gov/pubmed/35158913 http://dx.doi.org/10.3390/cancers14030647 |
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