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.
ASJC Scopus subject areas
- Cancer Research
- Pharmacology (medical)
Shiah, H. S., Chao, Y., Chen, L. T., Yao, T. J., Huang, J. D., Chang, J. Y., Chen, P. J., Chuang, T. R., Chin, Y. H., Whang-Peng, J., & Liu, T. W. (2006). Phase I and pharmacokinetic study of oral thalidomide in patients with advanced hepatocellular carcinoma. Cancer Chemotherapy and Pharmacology, 58(5), 654-664. https://doi.org/10.1007/s00280-006-0203-z