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Cancer Chemotherapy and Pharmacology

, Volume 58, Issue 5, pp 654–664 | Cite as

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
Original Article

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.

Keywords

Cirrhosis Maximum tolerated dose Angiogenesis inhibitor Hepatitis virus 

Notes

Acknowledgement

This work was supported by intramural grant of National Health Research Institutes, no. NHRI-89A1-CAQOVGHWRD.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Her-Shyong Shiah
    • 1
  • Yee Chao
    • 5
  • Li-Tzong Chen
    • 1
    • 2
  • Tzy-Jyun Yao
    • 3
  • Jin-Ding Huang
    • 4
    • 6
  • Jang-Yang Chang
    • 1
  • Pei-Jer Chen
    • 7
  • Tsai-Rong Chuang
    • 1
  • Yung-Hsin Chin
    • 1
  • Jacqueline Whang-Peng
    • 1
  • Tsang-Wu Liu
    • 1
  1. 1.Divisions of Cancer Research National Health Research InstitutesTaipeiTaiwan, ROC
  2. 2.Department of Internal MedicineKaohsiung Medical University HospitalKaohsiungTaiwan, ROC
  3. 3.Biostatistics & Bioinformatics and Biotechnology & Pharmaceutical Research National Health Research InstitutesTaipeiTaiwan, ROC
  4. 4.Biotechnology and Pharmaceutical ResearchNational Health Research InstitutesTaipeiTaiwan, ROC
  5. 5.Cancer Treatment CenterTaipei Veteran General HospitalTaipeiTaiwan, ROC
  6. 6.Department of Pharmacology Medical College of National Cheng-Kong UniversityTainanTaiwan, ROC
  7. 7.Graduate Institute of Clinical Medicine Medical College of National Taiwan University TaipeiTaiwan, ROC

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