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Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials

Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in p...

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Autores principales: Sprangers, Ben, Perazella, Mark A., Lichtman, Stuart M., Rosner, Mitchell H., Jhaveri, Kenar D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458993/
https://www.ncbi.nlm.nih.gov/pubmed/36090489
http://dx.doi.org/10.1016/j.ekir.2022.06.005
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author Sprangers, Ben
Perazella, Mark A.
Lichtman, Stuart M.
Rosner, Mitchell H.
Jhaveri, Kenar D.
author_facet Sprangers, Ben
Perazella, Mark A.
Lichtman, Stuart M.
Rosner, Mitchell H.
Jhaveri, Kenar D.
author_sort Sprangers, Ben
collection PubMed
description Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in patients with chronic kidney disease (CKD) is essential to guide treatment decisions. Typically, during drug development, initial clinical studies only include patients with normal or only mildly impaired kidney function. In subsequent preregistration studies, a limited number of patients with more severe kidney dysfunction are included. Data obtained from patients with either severe kidney dysfunction (here defined as an estimated glomerular filtration rate [eGFR] < 30 ml/min or stage 4G CKD) or end-stage kidney disease (ESKD) requiring kidney replacement treatment are particularly limited before drug registration and only a minority of new drug applications to the US Food and Drug Administration (FDA) include data from this population. Unfortunately, limited data and/or other safety concerns may result in a manufacturer statement that the drug is contraindicated in patients with advanced kidney disease, which hinders access to potentially beneficial drugs for these patients. This systemic exclusion of patients with CKD from cancer drug trials remains an unsolved problem, which prevents provision of optimal clinical care for these patients, raises questions of inclusion, diversity, and equity. In addition, with the aging of the population, there are increasing numbers of patients with CKD and cancer who face these issues. In this review, we evaluate the scientific basis to exclude patients with CKD from cancer trials and propose a comprehensive strategy to address this problem.
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spelling pubmed-94589932022-09-10 Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials Sprangers, Ben Perazella, Mark A. Lichtman, Stuart M. Rosner, Mitchell H. Jhaveri, Kenar D. Kidney Int Rep Review Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in patients with chronic kidney disease (CKD) is essential to guide treatment decisions. Typically, during drug development, initial clinical studies only include patients with normal or only mildly impaired kidney function. In subsequent preregistration studies, a limited number of patients with more severe kidney dysfunction are included. Data obtained from patients with either severe kidney dysfunction (here defined as an estimated glomerular filtration rate [eGFR] < 30 ml/min or stage 4G CKD) or end-stage kidney disease (ESKD) requiring kidney replacement treatment are particularly limited before drug registration and only a minority of new drug applications to the US Food and Drug Administration (FDA) include data from this population. Unfortunately, limited data and/or other safety concerns may result in a manufacturer statement that the drug is contraindicated in patients with advanced kidney disease, which hinders access to potentially beneficial drugs for these patients. This systemic exclusion of patients with CKD from cancer drug trials remains an unsolved problem, which prevents provision of optimal clinical care for these patients, raises questions of inclusion, diversity, and equity. In addition, with the aging of the population, there are increasing numbers of patients with CKD and cancer who face these issues. In this review, we evaluate the scientific basis to exclude patients with CKD from cancer trials and propose a comprehensive strategy to address this problem. Elsevier 2022-06-15 /pmc/articles/PMC9458993/ /pubmed/36090489 http://dx.doi.org/10.1016/j.ekir.2022.06.005 Text en © 2022 International Society of Nephrology. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Sprangers, Ben
Perazella, Mark A.
Lichtman, Stuart M.
Rosner, Mitchell H.
Jhaveri, Kenar D.
Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials
title Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials
title_full Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials
title_fullStr Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials
title_full_unstemmed Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials
title_short Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials
title_sort improving cancer care for patients with ckd: the need for changes in clinical trials
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458993/
https://www.ncbi.nlm.nih.gov/pubmed/36090489
http://dx.doi.org/10.1016/j.ekir.2022.06.005
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