Phase I and pharmacokinetic study of oral thalidomide in patients with advanced hepatocellular carcinoma
Journal
Cancer Chemotherapy and Pharmacology
Journal Volume
58
Journal Issue
5
Pages
654-664
Date Issued
2006
Author(s)
Shiah H.-S.
Chao Y.
Chen L.-T.
Yao T.-J.
Huang J.-D.
Chang J.-Y.
Chuang T.-R.
Chin Y.-H.
Whang-Peng J.
Liu T.-W.
Abstract
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. ? Springer-Verlag 2006.
Subjects
Angiogenesis inhibitor; Cirrhosis; Hepatitis virus; Maximum tolerated dose
SDGs
Other Subjects
alanine aminotransferase; antihistaminic agent; corticosteroid; hemoglobin; laxative; thado; thalidomide; abnormally high substrate concentration in blood; adult; advanced cancer; aged; alanine aminotransferase blood level; angioneurotic edema; area under the curve; article; bradycardia; cancer chemotherapy; cancer patient; clinical article; clinical trial; cohort analysis; constipation; controlled clinical trial; controlled study; correlation analysis; cystitis; disease severity; dizziness; drug absorption; drug blood level; drug determination; drug dose regimen; drug elimination; drug induced disease; drug safety; drug screening; dyspnea; esophagus varices bleeding; experience; female; fever; hair loss; Hepatitis B virus; Hepatitis C virus; human; leukopenia; liver cell carcinoma; liver dysfunction; male; maximum tolerated dose; mucosa inflammation; nonlinear system; periorbital edema; peripheral neuropathy; phase 1 clinical trial; priority journal; rash; sick sinus syndrome; somnolence; steady state; virus titration
Publisher
Springer Verlag
Type
journal article