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Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis
PURPOSE: For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068645/ https://www.ncbi.nlm.nih.gov/pubmed/36947209 http://dx.doi.org/10.1007/s00280-023-04514-x |
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author | Baum, Joanna Zickler, Daniel Bolbrinker, Juliane Richter, Rolf Braicu, Elena Ioana Grabowski, Jacek Sehouli, Jalid |
author_facet | Baum, Joanna Zickler, Daniel Bolbrinker, Juliane Richter, Rolf Braicu, Elena Ioana Grabowski, Jacek Sehouli, Jalid |
author_sort | Baum, Joanna |
collection | PubMed |
description | PURPOSE: For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis. METHODS: Blood and dialysate samples of the patient were collected on a dialysis and non-dialysis day. Olaparib total plasma concentrations were determined through high-performance liquid chromatography with tandem mass spectrometric detection. Actual scheduled sample times were used in the PK analysis to determine multiple dose PK parameters at steady state. RESULTS: Maximum concentration was achieved 1.5 h after drug administration on non- dialysis and after 1 h on dialysis day. The steady-state trough concentration and the maximal plasma concentration were similar on dialysis and non- dialysis day. On non-dialysis day, the AUC(ss) was 30% higher (24.0 µg.h/mL vs. 16.9 µg.h/ml) than on dialysis day. The plasma clearance CL(ss)/F was lower on non-dialysis day. Olaparib was not detectable in the dialysate samples. CONCLUSION: A total dose of olaparib 200 mg BID capsule formulation was well tolerated by our patient with ESRD and hemodialysis. Moreover, this maintenance therapy led to 16 months of progression free survival. Further trials on PARPi therapy in patients with hemodialysis are warranted. |
format | Online Article Text |
id | pubmed-10068645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-100686452023-04-04 Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis Baum, Joanna Zickler, Daniel Bolbrinker, Juliane Richter, Rolf Braicu, Elena Ioana Grabowski, Jacek Sehouli, Jalid Cancer Chemother Pharmacol Original Article PURPOSE: For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis. METHODS: Blood and dialysate samples of the patient were collected on a dialysis and non-dialysis day. Olaparib total plasma concentrations were determined through high-performance liquid chromatography with tandem mass spectrometric detection. Actual scheduled sample times were used in the PK analysis to determine multiple dose PK parameters at steady state. RESULTS: Maximum concentration was achieved 1.5 h after drug administration on non- dialysis and after 1 h on dialysis day. The steady-state trough concentration and the maximal plasma concentration were similar on dialysis and non- dialysis day. On non-dialysis day, the AUC(ss) was 30% higher (24.0 µg.h/mL vs. 16.9 µg.h/ml) than on dialysis day. The plasma clearance CL(ss)/F was lower on non-dialysis day. Olaparib was not detectable in the dialysate samples. CONCLUSION: A total dose of olaparib 200 mg BID capsule formulation was well tolerated by our patient with ESRD and hemodialysis. Moreover, this maintenance therapy led to 16 months of progression free survival. Further trials on PARPi therapy in patients with hemodialysis are warranted. Springer Berlin Heidelberg 2023-03-22 2023 /pmc/articles/PMC10068645/ /pubmed/36947209 http://dx.doi.org/10.1007/s00280-023-04514-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Baum, Joanna Zickler, Daniel Bolbrinker, Juliane Richter, Rolf Braicu, Elena Ioana Grabowski, Jacek Sehouli, Jalid Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
title | Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
title_full | Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
title_fullStr | Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
title_full_unstemmed | Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
title_short | Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
title_sort | olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068645/ https://www.ncbi.nlm.nih.gov/pubmed/36947209 http://dx.doi.org/10.1007/s00280-023-04514-x |
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