Monitoring Serum Levels of Sorafenib and Its N-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma
| Autor: | Masaru Mori, Hoshimi Okawa, Yuko Jin, Masaki Matsuura, Nariyasu Mano, Takahiro Maejima, Yasuteru Kondo, Kanehiko Hisamichi, Yuta Kataoka, Tooru Shimosegawa, Miki Shimada, Masamitsu Maekawa, Hiroyuki Suzuki |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Sorafenib
medicine.medical_specialty Palliative care medicine.diagnostic_test business.industry Area under the curve General Medicine urologic and male genital diseases medicine.disease Gastroenterology female genital diseases and pregnancy complications digestive system diseases General Biochemistry Genetics and Molecular Biology Pharmacokinetics Therapeutic drug monitoring Internal medicine Hepatocellular carcinoma medicine Carcinoma heterocyclic compounds Adverse effect business neoplasms medicine.drug |
| Zdroj: | The Tohoku Journal of Experimental Medicine. 237:173-182 |
| ISSN: | 1349-3329 0040-8727 |
| DOI: | 10.1620/tjem.237.173 |
| Popis: | Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUC(sorafenib) and AUC(N-oxide), respectively). Inter-group comparison revealed that AUC(N-oxide) and AUC ratio (AUC(N-oxide)/AUC(sorafenib)) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUC(N-oxide) and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUC(N-oxide:) 2.0 μg ∙ day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUC(N-oxide) ≤ 2.0 μg ∙ day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|