Association between pazopanib exposure and safety in Japanese patients with renal cell carcinoma or soft tissue sarcoma

Autor: Takeshi Aoyama, Kenji Nakano, Takeshi Yuasa, Erika Sugiyama, Takako Okawa, Kazuyuki Ito, Keiichi Azuma, Koki Hashimoto, Ryota Furutani, Makoto Hiraide, Kazuo Kobayashi, Kenichi Suzuki, Jyunnichi Tomomatsu, Masataka Tajima, Hitoshi Sato, Toshihiro Hama, Shunji Takahashi
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-9 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-28688-9
Popis: 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.
Databáze: Directory of Open Access Journals
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