Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma

There is a lack of understanding whether plasma levels of anticancer drugs (such as pazopanib) correlate with intra-tumoral levels and whether the plasma compartment is the best surrogate for pharmacokinetic and pharmacodynamic evaluation. Therefore, we aimed to quantify pazopanib concentrations in...

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Autores principales:	Laura Molenaar-Kuijsten, Milan van Meekeren, Remy B. Verheijen, Judith V. M. G. Bovée, Marta Fiocco, Bas Thijssen, Hilde Rosing, Alwin D. R. Huitema, Aisha B. Miah, Hans Gelderblom, Rick L. M. Haas, Neeltje Steeghs
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	intra-tumoral drug concentration neoadjuvant treatment pharmacokinetics tyrosine kinase inhibitor pazopanib soft tissue sarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c3f1d4b3365f4a8dad8a15b3f5a71773
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spelling	oai:doaj.org-article:c3f1d4b3365f4a8dad8a15b3f5a717732021-11-25T17:03:53ZIntra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma10.3390/cancers132257802072-6694https://doaj.org/article/c3f1d4b3365f4a8dad8a15b3f5a717732021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5780https://doaj.org/toc/2072-6694There is a lack of understanding whether plasma levels of anticancer drugs (such as pazopanib) correlate with intra-tumoral levels and whether the plasma compartment is the best surrogate for pharmacokinetic and pharmacodynamic evaluation. Therefore, we aimed to quantify pazopanib concentrations in tumor tissue, to assess the correlation between tumor concentrations and plasma concentrations and between tumor concentrations and efficacy. In this clinical trial, non-metastatic STS patients were treated with neo-adjuvant concurrent radiotherapy and pazopanib. Plasma samples and tumor biopsies were collected, and pazopanib concentrations were measured using liquid chromatography-tandem mass spectrometry. Twenty-four evaluable patients were included. The median pazopanib tumor concentration was 19.2 µg/g (range 0.149–200 µg/g). A modest correlation was found between tumor concentrations and plasma levels of pazopanib (<i>ρ</i> = 0.41, <i>p</i> = 0.049). No correlation was found between tumor concentrations and percentage of viable tumor cells (<i>p</i> > 0.05); however, a trend towards less viable tumor cells in patients with high pazopanib concentrations in tumor tissue was observed in a categorical analysis. Possible explanations for the lack of correlation might be heterogeneity of the tumors and timing of the biopsy procedure.Laura Molenaar-KuijstenMilan van MeekerenRemy B. VerheijenJudith V. M. G. BovéeMarta FioccoBas ThijssenHilde RosingAlwin D. R. HuitemaAisha B. MiahHans GelderblomRick L. M. HaasNeeltje SteeghsMDPI AGarticleintra-tumoral drug concentrationneoadjuvant treatmentpharmacokineticstyrosine kinase inhibitorpazopanibsoft tissue sarcomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5780, p 5780 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intra-tumoral drug concentration neoadjuvant treatment pharmacokinetics tyrosine kinase inhibitor pazopanib soft tissue sarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	intra-tumoral drug concentration neoadjuvant treatment pharmacokinetics tyrosine kinase inhibitor pazopanib soft tissue sarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Laura Molenaar-Kuijsten Milan van Meekeren Remy B. Verheijen Judith V. M. G. Bovée Marta Fiocco Bas Thijssen Hilde Rosing Alwin D. R. Huitema Aisha B. Miah Hans Gelderblom Rick L. M. Haas Neeltje Steeghs Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
description	There is a lack of understanding whether plasma levels of anticancer drugs (such as pazopanib) correlate with intra-tumoral levels and whether the plasma compartment is the best surrogate for pharmacokinetic and pharmacodynamic evaluation. Therefore, we aimed to quantify pazopanib concentrations in tumor tissue, to assess the correlation between tumor concentrations and plasma concentrations and between tumor concentrations and efficacy. In this clinical trial, non-metastatic STS patients were treated with neo-adjuvant concurrent radiotherapy and pazopanib. Plasma samples and tumor biopsies were collected, and pazopanib concentrations were measured using liquid chromatography-tandem mass spectrometry. Twenty-four evaluable patients were included. The median pazopanib tumor concentration was 19.2 µg/g (range 0.149–200 µg/g). A modest correlation was found between tumor concentrations and plasma levels of pazopanib (<i>ρ</i> = 0.41, <i>p</i> = 0.049). No correlation was found between tumor concentrations and percentage of viable tumor cells (<i>p</i> > 0.05); however, a trend towards less viable tumor cells in patients with high pazopanib concentrations in tumor tissue was observed in a categorical analysis. Possible explanations for the lack of correlation might be heterogeneity of the tumors and timing of the biopsy procedure.
format	article
author	Laura Molenaar-Kuijsten Milan van Meekeren Remy B. Verheijen Judith V. M. G. Bovée Marta Fiocco Bas Thijssen Hilde Rosing Alwin D. R. Huitema Aisha B. Miah Hans Gelderblom Rick L. M. Haas Neeltje Steeghs
author_facet	Laura Molenaar-Kuijsten Milan van Meekeren Remy B. Verheijen Judith V. M. G. Bovée Marta Fiocco Bas Thijssen Hilde Rosing Alwin D. R. Huitema Aisha B. Miah Hans Gelderblom Rick L. M. Haas Neeltje Steeghs
author_sort	Laura Molenaar-Kuijsten
title	Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
title_short	Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
title_full	Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
title_fullStr	Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
title_full_unstemmed	Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
title_sort	intra-tumoral pharmacokinetics of pazopanib in combination with radiotherapy in patients with non-metastatic soft-tissue sarcoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c3f1d4b3365f4a8dad8a15b3f5a71773
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Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma

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