Abstract

The safety and effectiveness of pazopanib are related to plasma trough concentrations in renal cell carcinoma (RCC); however, data on pazopanib plasma trough concentrations with soft tissue sarcoma (STS) are limited. This study investigated the relationship between plasma trough concentrations and pazopanib safety in 45 Japanese patients with RCC or STS. Among the 33 patients included, the median pazopanib trough concentration was 37.5 (range, 12.1–67.6) µg/mL, which was not significantly different between Japanese RCC and STS patients. The plasma trough concentrations showed significant and positive correlations with aspartate aminotransferase and alanine aminotransferase values in blood samples taken for pharmacokinetic measurements after the administration. The incidence of pazopanib treatment discontinuation were significantly higher in RCC patients (p = 0.027). The primary reason for treatment discontinuation was hepatic dysfunction (5/6, 83.3%). Furthermore, this study revealed that pazopanib trough concentration was affected significantly by proton pump inhibitors but not by histamine 2-receptor blockers. In conclusion, the observed pazopanib trough levels and their safety in the Japanese RCC and STS populations in this study were similar to those of the global population. This is the first study to correlate the hepatotoxicity and pharmacokinetic property of pazopanib plasma trough levels by comparing Japanese patients with RCC or STS.

Details

Title
Association between pazopanib exposure and safety in Japanese patients with renal cell carcinoma or soft tissue sarcoma
Author
Aoyama, Takeshi 1 ; Nakano, Kenji 2 ; Yuasa, Takeshi 3 ; Sugiyama, Erika 4 ; Okawa, Takako 5 ; Ito, Kazuyuki 5 ; Azuma, Keiichi 5 ; Hashimoto, Koki 5 ; Furutani, Ryota 5 ; Hiraide, Makoto 6 ; Kobayashi, Kazuo 5 ; Suzuki, Kenichi 6 ; Tomomatsu, Jyunnichi 2 ; Tajima, Masataka 4 ; Sato, Hitoshi 4 ; Hama, Toshihiro 5 ; Takahashi, Shunji 2 

 Japanese Foundation for Cancer Research, Department of Pharmacy, Cancer Institute Hospital, Tokyo, Japan (GRID:grid.410807.a) (ISNI:0000 0001 0037 4131); Showa University, Division of Pharmacokinetics and Pharmacodynamics, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
 Japanese Foundation for Cancer Research, Department of Medical Oncology, The Cancer Institute Hospital, Tokyo, Japan (GRID:grid.410807.a) (ISNI:0000 0001 0037 4131) 
 Japanese Foundation for Cancer Research, Department of Urology, The Cancer Institute Hospital, Tokyo, Japan (GRID:grid.410807.a) (ISNI:0000 0001 0037 4131) 
 Showa University, Division of Pharmacokinetics and Pharmacodynamics, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
 Japanese Foundation for Cancer Research, Department of Pharmacy, Cancer Institute Hospital, Tokyo, Japan (GRID:grid.410807.a) (ISNI:0000 0001 0037 4131) 
 Japanese Foundation for Cancer Research, Department of Pharmacy, Cancer Institute Hospital, Tokyo, Japan (GRID:grid.410807.a) (ISNI:0000 0001 0037 4131); Hoshi University Division of Applied Pharmaceutical Education and Research Ebara, Tokyo, Japan (GRID:grid.412239.f) (ISNI:0000 0004 1770 141X) 
Pages
2099
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2773494439
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.