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Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2020 Jul; Vol. 86 (1), pp. 129-139. Date of Electronic Publication: 2020 Jun 25. - Publication Year :
- 2020
-
Abstract
- 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).<br />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).<br />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 <0.05] and 1.40 μg/mL (AUC 0.97, 95% CI 0.97-1.00; p <0.05), respectively. OS of patients with sorafenib 1.40-3.45 µg/mL had a tendency to be longer than those of patients administered < 1.40 μg/mL and ≥ 3.45 μg/mL [median 17.8 months (1.40-3.45 μg/mL) vs. 5.3 months (< 1.40 μg/mL) and 9.5 months (≥ 3.45 μg/mL)].<br />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.
- Subjects :
- Aged
Aged, 80 and over
Antineoplastic Agents adverse effects
Antineoplastic Agents blood
Antineoplastic Agents pharmacokinetics
Carcinoma, Hepatocellular mortality
Female
Humans
Liver Neoplasms mortality
Male
Middle Aged
Retrospective Studies
Sorafenib adverse effects
Sorafenib blood
Sorafenib pharmacokinetics
Treatment Outcome
Antineoplastic Agents therapeutic use
Carcinoma, Hepatocellular drug therapy
Liver Neoplasms drug therapy
Sorafenib therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 86
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32588123
- Full Text :
- https://doi.org/10.1007/s00280-020-04105-0