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

详细信息    查看全文

• 作者：Her-Shyong Shiah ; Yee Chao ; Li-Tzong Chen ; Tzy-Jyun Yao ; Jin-Ding Huang ; Jang-Yang Chang ; Pei-Jer Chen ; Tsai-Rong Chuang ; Yung-Hsin Chin and Jacqueline Whang-Peng ; et al.
• 关键词：Cirrhosis ; Maximum tolerated dose ; Angiogenesis inhibitor ; Hepatitis virus
• 刊名：Cancer Chemotherapy and Pharmacology
• 出版年：2006
• 出版时间：November, 2006
• 年：2006
• 卷：58
• 期：5
• 页码：654-664
• 全文大小：283 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Pharmacology and Toxicology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0843

文摘

Purpose: To evaluate the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics of thalidomide in patients with advanced hepatocellular carcinoma (HCC). Methods: 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. Results: 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. Conclusion: The absorption and elimination of thalidomide are not significantly different in HCC patients with compensated or decompensated hepatic dysfunction.