Phase I and pharmacokinetic study of oral thalidomide in patients with advanced hepatocellular carcinoma

Cancer Chemotherapy and Pharmacology
Her-Shyong ShiahTsang-Wu Liu

Abstract

To evaluate the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics of thalidomide in patients with advanced hepatocellular carcinoma (HCC). Patients with advanced HCC who were not feasible for definitive local therapy were eligible. Patients were enrolled in a cohort of three to receive thalidomide twice daily for 1 week to determine the MTD. Intra-patient dose escalation was permitted. Pharmacokinetic studies were performed at the first dose level and repeated at the second dose level of each patient. Fifteen patients were accrued at four dose levels with the starting dose range 100-400 mg/day. Two patients at 400 mg/day experienced DLT (grade 3 angioedema and dyspnea, respectively). The MTD of twice-daily schedule was determined as 300 mg/day. The mean steady-state maximal blood concentration and mean steady-state area under the curve had a trend toward positive correlation, but non-linear proportionate, to the daily dose of thalidomide. Pharmacokinetic parameters are comparable for patients of Child-Pugh's A and B. Apparent mild, transient drug-induced transaminitis was early onset, self-limited, which occurred in 30.7% of patients. Serum hepatitis B or C viral titers was largely not affected....Continue Reading

References

Jan 3, 1991·The New England Journal of Medicine·N WeidnerJ Folkman
Jan 1, 1991·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R S Kerbel
Mar 1, 1991·The Journal of Experimental Medicine·E P SampaioG Kaplan
Jan 1, 1986·Toxicology and Applied Pharmacology·A G BraunS L Weinreb
Feb 1, 1971·The Journal of Experimental Medicine·J FolkmanG Williams
Nov 18, 1971·The New England Journal of Medicine·J Folkman
Aug 12, 1971·The New England Journal of Medicine·J Folkman
Jan 1, 1981·Cancer·A B MillerA Winkler
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·R J D'AmatoJ Folkman
Jun 1, 1993·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K IkedaH Kumada
Nov 26, 1997·Lancet·A R Wettstein, A P Meagher
Jul 1, 1998·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·F E KruseH E Völcker
Jan 6, 1999·Journal of Pharmaceutical Sciences·W D FiggE Reed
Nov 24, 1999·The New England Journal of Medicine·S SinghalB Barlogie
Feb 16, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H A FineW K Yung
Mar 11, 2000·Journal of Biochemical and Molecular Toxicology·S K TeoS D Thomas
Jun 17, 2000·American Journal of Clinical Oncology·Y Z PattK A Waugh
Jul 13, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R F LittleR Yarchoan
Jul 15, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S M BaidasD F Hayes
Apr 3, 2001·American Journal of Hematology·R Fowler, K Imrie
Jun 14, 2001·Journal of Clinical Pharmacology·S K TeoS D Thomas
Aug 16, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M A DimopoulosP Panayiotidis
Jan 5, 2002·Journal of Neuro-oncology·G M MarxH R Wheeler
Jan 5, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert J MotzerMadhu Mazumdar
Jan 25, 2002·Blood·Martin B SteinsRolf M Mesters
Feb 15, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·N AbramsonJeffrey M Harris
Jun 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wen-Jen HwuAlan N Houghton
Aug 16, 2002·Medical Oncology·M MerupUNKNOWN Swedish National Study Group on Chronic Myeloproliferative Disorders
Dec 20, 2003·The Lancet Oncology·Martina Habeck
Jan 24, 2004·The Journal of Pharmacy and Pharmacology·T ErikssonG A Kaysen
Mar 3, 2004·World Journal of Gastroenterology : WJG·Tsang-En WangRuey-Kuen Hsieh
Jul 28, 2004·Annals of Oncology : Official Journal of the European Society for Medical Oncology·V Eleutherakis-PapaiakovouM A Dimopoulos
Oct 7, 2004·The American Journal of Medicine·Meletios A Dimopoulos, Vagelis Eleutherakis-Papaiakovou
Aug 11, 2005·Alimentary Pharmacology & Therapeutics·L-T ChenJ Whang-Peng

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Citations

Nov 16, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·Stephanie CoulonHans Van Vlierberghe
Nov 21, 2012·Drug Metabolism and Pharmacokinetics·Katsunori NakamuraTamihide Matsunaga
Feb 1, 2011·International Journal of Radiation Oncology, Biology, Physics·Hui-Ju Ch'angLi-Tzong Chen
Jun 23, 2010·Journal of Gastroenterology·Ying-Chun ShenAnn-Lii Cheng
Aug 12, 2015·World Journal of Hepatology·Hui-Ju Ch'ang

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