Document Detail


Pharmacokinetic and clinical phase II trial of imatinib in patients with impaired liver function and advanced hepatocellular carcinoma.
MedLine Citation:
PMID:  16319507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: No effective chemotherapy for advanced hepatocellular carcinoma (HCC) exists. Expression of the platelet-derived growth factor receptor (PDGFR) has been demonstrated in HCC, which may derive from hepatic stem cells that express c-kit. The aim of this trial was to evaluate imatinib, a tyrosine kinase inhibitor of PDGFR and c-kit, in patients with advanced HCC and impaired liver function. PATIENTS AND METHODS: Patients were treated with 400-600 mg imatinib daily. Immunohistochemical staining was performed for PDGFR and c-kit. Response was assessed by CT scans every 8 weeks. For pharmacokinetics studies, 74 plasma samples were assessed. RESULTS: Of the 17 patients enrolled in the study, 15 were evaluable for response. Only 1 tumor was positive for PDGFR and none was positive for c-kit. Grade 3/4 neutropenia occurred in 2 patients (1 had neutropenic fever). There was no objective response, and 5 (33%) patients had stable disease. Median time to treatment failure was 1.8 months in the whole study cohort and 3.7 months in the patients with stable disease. Patients treated with 400 mg imatinib did not significantly differ in pharmacokinetics from patients with chronic myelogenous leukemia (CML). CONCLUSION: In this small group of patients with advanced, mostly PDGFR- and c-kit-negative HCC, imatinib showed no therapeutic effect. In contrast to CML patients, the pharmacokinetics of imatinib were not significantly affected by impaired liver function.
Authors:
F Eckel; S von Delius; M Mayr; M Dobritz; F Fend; C Hosius; E Schleyer; E Schulte-Frohlinde; R M Schmid; C Lersch
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article     Date:  2005-11-24
Journal Detail:
Title:  Oncology     Volume:  69     ISSN:  0030-2414     ISO Abbreviation:  Oncology     Publication Date:  2005  
Date Detail:
Created Date:  2005-12-14     Completed Date:  2006-01-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0135054     Medline TA:  Oncology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  363-71     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Germany. florian.eckel@lrz.tum.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antineoplastic Agents / pharmacology*
Carcinoma, Hepatocellular / drug therapy*
Cohort Studies
Disease-Free Survival
Enzyme Inhibitors / pharmacology
Fibrosis
Humans
Immunohistochemistry
Liver / metabolism
Liver Neoplasms / drug therapy*
Middle Aged
Piperazines / pharmacology*
Protein Kinase Inhibitors / pharmacology*
Protein-Tyrosine Kinases / antagonists & inhibitors
Proto-Oncogene Proteins c-kit / biosynthesis
Pyrimidines / pharmacology*
Receptors, Platelet-Derived Growth Factor / biosynthesis
Stem Cells / metabolism
Time Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 152459-95-5/imatinib; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Proto-Oncogene Proteins c-kit; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor

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