Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study

Autor: Hiroya Iida, Sachiko Tanaka-Mizuno, Akira Andoh, Takehide Fujimoto, Rie Osaki, Daiki Hira, Satoshi Noda, Masaji Tani, Yoshito Ikeda, Tomohiro Terada, Shin-ya Morita
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Sorafenib
Cancer Research
medicine.medical_specialty
Carcinoma
Hepatocellular
Hepatocellular carcinoma
Antineoplastic Agents
urologic and male genital diseases
Toxicology
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Internal medicine
medicine
Humans
heterocyclic compounds
Pharmacology (medical)
Trough Concentration
Adverse effect
neoplasms
Aged
Retrospective Studies
Aged
80 and over
Pharmacology
business.industry
Liver Neoplasms
Area under the curve
Retrospective cohort study
Middle Aged
medicine.disease
Personalized pharmacotherapy
female genital diseases and pregnancy complications
digestive system diseases
Confidence interval
Treatment Outcome
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Female
business
medicine.drug
Zdroj: Cancer Chemotherapy and Pharmacology. 86:129-139
ISSN: 1432-0843
0344-5704
DOI: 10.1007/s00280-020-04105-0
Popis: Purpose:Severe adverse events frequently occur in patients treated with sorafenib, whereas some patients have suboptimal response to sorafenib. We aimed to evaluate the association of sorafenib-induced toxicities and clinical outcomes with the pharmacokinetics of sorafenib in patients with hepatocellular carcinoma (HCC).
Methods:This was a retrospective, observational study in which 26 HCC patients who had been treated with sorafenib were enrolled between September 2010 and March 2015. The association between trough sorafenib concentration and occurrence of grade ≥ 3 toxicities was evaluated. In addition, we estimated the association of trough sorafenib concentration with overall survival (OS).
Results:The median sorafenib concentration was 2.91 μg/mL (range 0.74-8.8 μg/mL). Based on the receiver operating characteristic curve, the threshold value of the trough sorafenib concentration for predicting grade ≥ 3 toxicities and responder (complete response or partial response at best response, or stable disease for ≥ 3 months) was 3.45 μg/mL [area under the curve (AUC) 0.74, 95% confidence interval (CI) 0.54-0.93; p
Conclusions:From results of this study, we proposed that the target range of sorafenib may be a trough concentration of 1.40-3.45 μg/mL in patients with HCC.
Databáze: OpenAIRE
Externí odkaz: