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.
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 CMLpatients, the pharmacokinetics of imatinib were not significantly affected by impaired liver function.
Authors: Thomas Kamenz; Karel Caca; Thilo Blüthner; Andrea Tannapfel; Joachim Mössner; Marcus Wiedmann Journal: World J Gastroenterol Date: 2006-03-14 Impact factor: 5.742
Authors: Andrew X Zhu; Dushyant V Sahani; Dan G Duda; Emmanuelle di Tomaso; Marek Ancukiewicz; Onofrio A Catalano; Vivek Sindhwani; Lawrence S Blaszkowsky; Sam S Yoon; Johanna Lahdenranta; Pankaj Bhargava; Jeffrey Meyerhardt; Jeffrey W Clark; Eunice L Kwak; Aram F Hezel; Rebecca Miksad; Thomas A Abrams; Peter C Enzinger; Charles S Fuchs; David P Ryan; Rakesh K Jain Journal: J Clin Oncol Date: 2009-05-26 Impact factor: 44.544
Authors: Yunching Chen; Yuhui Huang; Thomas Reiberger; Annique M Duyverman; Peigen Huang; Rekha Samuel; Lotte Hiddingh; Sylvie Roberge; Christina Koppel; Gregory Y Lauwers; Andrew X Zhu; Rakesh K Jain; Dan G Duda Journal: Hepatology Date: 2014-02-18 Impact factor: 17.425