Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters
| Autor: | Hung Chi Tai, Tung Hu Tsai, Yu Chuen Huang, Chen-Hsi Hsieh, Li-Ying Wang, Yu Jen Chen, Hsiang Ling Huang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Hepatocellular carcinoma medicine.medical_treatment lcsh:Medicine Rats Sprague-Dawley Cytochrome P-450 CYP3A Tissue Distribution lcsh:Science Venous Thrombosis Multidisciplinary Portal Vein Liver Neoplasms NF-kappa B Sorafenib Drug regulation Combined Modality Therapy Thrombosis Specific Pathogen-Free Organisms Enzyme Induction Cyclosporine medicine.drug medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Carcinoma Hepatocellular Urology Antineoplastic Agents Radiosurgery Article Text mining Pharmacokinetics In vivo Cell Line Tumor medicine Animals Humans Protein Kinase Inhibitors neoplasms Retrospective Studies CYP3A4 business.industry lcsh:R Dose-Response Relationship Radiation medicine.disease Rats Radiation therapy Regimen Cytochrome P-450 CYP3A Inhibitors lcsh:Q business |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-66583-9 |
| Popis: | To evaluate the effect and mechanism of radiotherapy (RT)–sorafenib pharmacokinetics (PK) in different regimens with conventional or high dose irradiation. Between February 2012 and December 2018, 43 patients with portal vein tumor thrombosis treated with sorafenib plus conventional RT (58%) or stereotactic body radiation therapy (SBRT, 42%) were retrospectively reviewed. In vivo and in vitro studies of concurrent and sequential RT with sorafenib were designed. SBRT resulted in a 3-fold increase in complete recanalization compared to conventional RT group (28% vs. 8%, p = 0.014). Compared to the control group, the area under the concentration vs. time curve (AUC) of sorafenib was increased in the concurrent RT2Gy and RT9Gy groups and the sequential RT9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential RT2Gy group (p = 0.036). Sequential RT2Gy and RT9Gy increased CYP3A4 activity by 82% (p = 0.028) and 203% (p = 0.0004), respectively, compared to that with the corresponding concurrent regimen. SBRT produced better recanalization than conventional RT with sorafenib. The AUC of sorafenib was modulated by RT. P-gp expression was not influenced by RT. The sequential RT regimen increased CYP3A4 activity that may increase the RT-sorafenib synergy effect and overall sorafenib activity. The biodistribution of sorafenib was modulated by local RT with the different regimens. |
| Databáze: | OpenAIRE |
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