Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma
| Autor: | Bas Thijssen, Hans Gelderblom, Milan van Meekeren, Aisha Miah, Rick L. Haas, Laura Molenaar-Kuijsten, Judith V.M.G. Bovée, Alwin D. R. Huitema, Neeltje Steeghs, Hilde Rosing, Marta Fiocco, Remy B. Verheijen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
neoadjuvant treatment Cancer Research medicine.medical_specialty medicine.drug_class medicine.medical_treatment Tyrosine-kinase inhibitor Article Pazopanib tyrosine kinase inhibitor Pharmacokinetics Internal medicine medicine pazopanib In patient RC254-282 business.industry Soft tissue sarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Clinical trial Radiation therapy Pharmacodynamics soft tissue sarcoma intra-tumoral drug concentration business pharmacokinetics medicine.drug |
| Zdroj: | Cancers Volume 13 Issue 22 Cancers, Vol 13, Iss 5780, p 5780 (2021) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13225780 |
| Popis: | 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 (ρ = 0.41, p = 0.049). No correlation was found between tumor concentrations and percentage of viable tumor cells (p > 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. |
| Databáze: | OpenAIRE |
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