Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters
Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin cleara...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/23/5963 |
| _version_ | 1797507997039067136 |
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| author | Mirjam E. van de Velde Emil den Bakker Hester N. Blufpand Gertjan L. Kaspers Floor C. H. Abbink Arjenne W. A. Kors Abraham J. Wilhelm Richard J. Honeywell Godefridus J. Peters Birgit Stoffel-Wagner Laurien M. Buffart Arend Bökenkamp |
| author_facet | Mirjam E. van de Velde Emil den Bakker Hester N. Blufpand Gertjan L. Kaspers Floor C. H. Abbink Arjenne W. A. Kors Abraham J. Wilhelm Richard J. Honeywell Godefridus J. Peters Birgit Stoffel-Wagner Laurien M. Buffart Arend Bökenkamp |
| author_sort | Mirjam E. van de Velde |
| collection | DOAJ |
| description | Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. In 13 children with retinoblastoma 38 carboplatin clearance values were obtained from individual fits using MWPharm++. Carboplatin exposure (AUC) was calculated from administered dose and observed carboplatin clearance and compared to predicted AUC calculated with a carboplatin dosing equation (Newell) using different GFR estimates. Different dosing regimens were compared in terms of accuracy, bias and precision. All patients had normal eGFR. Carboplatin exposure using cystatin C-based eGFR equations tended to be more accurate compared to creatinine-based eGFR (30% accuracy 76.3–89.5% versus 76.3–78.9%, respectively), which led to significant overexposure, especially in younger (aged ≤ 2 years) children. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. Although anthropometric dosing performed comparably to many of the eGFR equations overall, we observed a weight-dependent change in bias leading to underdosing in the smallest patients. Using cystatin C-based eGFR equations for carboplatin dosing in children leads to more accurate carboplatin-exposure in patients with normal renal function compared to anthropometric dosing. In children with impaired kidney function, this trend might be more pronounced. Anthropometric dosing is hampered by a weight-dependent bias. |
| first_indexed | 2024-03-10T04:56:21Z |
| format | Article |
| id | doaj.art-9002511678574bec98977119aac40dd1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:56:21Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9002511678574bec98977119aac40dd12023-11-23T02:12:14ZengMDPI AGCancers2072-66942021-11-011323596310.3390/cancers13235963Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation MattersMirjam E. van de Velde0Emil den Bakker1Hester N. Blufpand2Gertjan L. Kaspers3Floor C. H. Abbink4Arjenne W. A. Kors5Abraham J. Wilhelm6Richard J. Honeywell7Godefridus J. Peters8Birgit Stoffel-Wagner9Laurien M. Buffart10Arend Bökenkamp11Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Nephrology, 1081 HV Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC, Amsterdam Medical Center, Pediatric Oncology, 1081 HV Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Vrije Universiteit Amsterdam, Clinical Pharmacology and Pharmacy, 1081 HV Amsterdam, The NetherlandsLaboratory of Medical Oncology, Amsterdam University Medical Center, VUMC, 1081 HV Amsterdam, The NetherlandsLaboratory of Medical Oncology, Amsterdam University Medical Center, VUMC, 1081 HV Amsterdam, The NetherlandsInstitute for Clinical Chemistry and Clinical Pharmacology, University of Bonn-Medical Center, 53127 Bonn, GermanyDepartment of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Nephrology, 1081 HV Amsterdam, The NetherlandsRenal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. In 13 children with retinoblastoma 38 carboplatin clearance values were obtained from individual fits using MWPharm++. Carboplatin exposure (AUC) was calculated from administered dose and observed carboplatin clearance and compared to predicted AUC calculated with a carboplatin dosing equation (Newell) using different GFR estimates. Different dosing regimens were compared in terms of accuracy, bias and precision. All patients had normal eGFR. Carboplatin exposure using cystatin C-based eGFR equations tended to be more accurate compared to creatinine-based eGFR (30% accuracy 76.3–89.5% versus 76.3–78.9%, respectively), which led to significant overexposure, especially in younger (aged ≤ 2 years) children. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. Although anthropometric dosing performed comparably to many of the eGFR equations overall, we observed a weight-dependent change in bias leading to underdosing in the smallest patients. Using cystatin C-based eGFR equations for carboplatin dosing in children leads to more accurate carboplatin-exposure in patients with normal renal function compared to anthropometric dosing. In children with impaired kidney function, this trend might be more pronounced. Anthropometric dosing is hampered by a weight-dependent bias.https://www.mdpi.com/2072-6694/13/23/5963carboplatinchildrenrenal function-based dosingglomerular filtration ratecystatin Cretinoblastoma |
| spellingShingle | Mirjam E. van de Velde Emil den Bakker Hester N. Blufpand Gertjan L. Kaspers Floor C. H. Abbink Arjenne W. A. Kors Abraham J. Wilhelm Richard J. Honeywell Godefridus J. Peters Birgit Stoffel-Wagner Laurien M. Buffart Arend Bökenkamp Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters Cancers carboplatin children renal function-based dosing glomerular filtration rate cystatin C retinoblastoma |
| title | Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters |
| title_full | Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters |
| title_fullStr | Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters |
| title_full_unstemmed | Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters |
| title_short | Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters |
| title_sort | carboplatin dosing in children using estimated glomerular filtration rate equation matters |
| topic | carboplatin children renal function-based dosing glomerular filtration rate cystatin C retinoblastoma |
| url | https://www.mdpi.com/2072-6694/13/23/5963 |
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