Universität zu Köln

Fucile, Carmen, Marenco, Simona, Bazzica, Marco, Zuccoli, Maria Laura, Lantieri, Francesca, Robbiano, Luigi, Marini, Valeria, Di Gion, Paola, Pieri, Giulia, Stura, Paola, Martelli, Antonietta, Savarino, Vincenzo, Mattioli, Francesca and Picciotto, Antonino (2015). Measurement of sorafenib plasma concentration by high-performance liquid chromatography in patients with advanced hepatocellular carcinoma: is it useful the application in clinical practice? A pilot study. Med. Oncol., 32 (1). TOTOWA: HUMANA PRESS INC. ISSN 1559-131X

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Abstract

Pharmacokinetics and dose-finding studies on sorafenib were conducted on heterogeneous groups of patients with solid tumors. Portal hypertension, gut motility impairment and altered bile enterohepatic circulation may explain different sorafenib toxicological profile in cirrhotic patients. This study evaluated sorafenib plasma concentration in a homogeneous group of cirrhotic patients with hepatocellular carcinoma (HCC). Sorafenib concentrations were determined by liquid chromatography in 12 consecutive patients. Data have been evaluated by the generalized estimating equations method (p value statistical level was set at alpha = 0.05). (1) There were not significant differences between sorafenib concentrations in patients who tolerate the full dose versus patients with reduced dose due to toxicity; (2) the average sorafenib concentrations measured 3 h after the morning dosing were lower than those measured 12 h after the evening dosing (p = 0.005); (3) sorafenib concentrations decrease overtime (p < 10(-4)); (4) it has been found an association between the development of severe adverse reactions and sorafenib concentrations (p < 10(-5)). The relationship between dose and concentration of sorafenib in HCC patients is poor and not clinically predictable, confirming the variability both in the maximum tolerated dose and in plasma concentrations. Several factors may influence the pharmacokinetics in patients with liver disease. This may explain the inter-patient variability of concentrations and the lack of differences in concentration at different dosages. It could be interesting to extend the series of HCC patients to enhance information on the kinetics of the drug; furthermore, to establish a threshold of plasma sorafenib concentrations to predict severe adverse reactions would be clinically useful.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fucile, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED Marenco, Simona UNSPECIFIED UNSPECIFIED UNSPECIFIED Bazzica, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuccoli, Maria Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Lantieri, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Robbiano, Luigi UNSPECIFIED UNSPECIFIED UNSPECIFIED Marini, Valeria UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Gion, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Pieri, Giulia UNSPECIFIED UNSPECIFIED UNSPECIFIED Stura, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Martelli, Antonietta UNSPECIFIED UNSPECIFIED UNSPECIFIED Savarino, Vincenzo UNSPECIFIED UNSPECIFIED UNSPECIFIED Mattioli, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Picciotto, Antonino UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-417289
DOI:	10.1007/s12032-014-0335-7
Journal or Publication Title:	Med. Oncol.
Volume:	32
Number:	1
Date:	2015
Publisher:	HUMANA PRESS INC
Place of Publication:	TOTOWA
ISSN:	1559-131X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FACTOR RECEPTOR INHIBITOR; PHASE-I; RAF/MEK/ERK PATHWAY; ANTITUMOR-ACTIVITY; RAF KINASE; PHARMACOKINETICS; BAY-43-9006; EXPOSURE; SAFETY; TIME Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41728