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

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, Jacqueline Whang-Peng, Tsang Wu Liu

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)654-664
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume58
Issue number5
DOIs
Publication statusPublished - Jan 1 2006
Externally publishedYes

Fingerprint

Thalidomide
Pharmacokinetics
Hepatocellular Carcinoma
Toxicity
Maximum Tolerated Dose
Blood
Angioedema
Pharmaceutical Preparations
Hepatitis C
Hepatitis B
Dyspnea
Area Under Curve
Appointments and Schedules

Keywords

  • Angiogenesis inhibitor
  • Cirrhosis
  • Hepatitis virus
  • Maximum tolerated dose

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Phase I and pharmacokinetic study of oral thalidomide in patients with advanced hepatocellular carcinoma. / Shiah, Her Shyong; Chao, Yee; Chen, Li Tzong; Yao, Tzy Jyun; Huang, Jin Ding; Chang, Jang Yang; Chen, Pei Jer; Chuang, Tsai Rong; Chin, Yung Hsin; Whang-Peng, Jacqueline; Liu, Tsang Wu.

In: Cancer Chemotherapy and Pharmacology, Vol. 58, No. 5, 01.01.2006, p. 654-664.

Research output: Contribution to journalArticle

Shiah, Her Shyong ; Chao, Yee ; Chen, Li Tzong ; Yao, Tzy Jyun ; Huang, Jin Ding ; Chang, Jang Yang ; Chen, Pei Jer ; Chuang, Tsai Rong ; Chin, Yung Hsin ; Whang-Peng, Jacqueline ; Liu, Tsang Wu. / Phase I and pharmacokinetic study of oral thalidomide in patients with advanced hepatocellular carcinoma. In: Cancer Chemotherapy and Pharmacology. 2006 ; Vol. 58, No. 5. pp. 654-664.
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AU - Chao, Yee

AU - Chen, Li Tzong

AU - Yao, Tzy Jyun

AU - Huang, Jin Ding

AU - Chang, Jang Yang

AU - Chen, Pei Jer

AU - Chuang, Tsai Rong

AU - Chin, Yung Hsin

AU - Whang-Peng, Jacqueline

AU - Liu, Tsang Wu

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N2 - 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.

AB - 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.

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