A pilot sutdy of thalidomide in patients with advanced hepatocellular carcinoma

LT Chen, MD, PhD a, Y Chao, MD, PhD b, AL Cheng, MD, PhD c, TW Liu, MD a, J Whang-Peng, MD a

National Health Research Institutes a, Veteran General Hospital b, National Taiwan University c, Taipei, Taiwan

AIMS: To evaluate the efficacy of an angiogenesis inhibitor, thalidomide, in advanced hepatocellular carcinoma (HCC). Patients and Methods: Forty-two patients of metastatic or locally advanced HCC who had received oral thalidomide from either a name-listed compassionate use program (n= 27) or a phase I/dose escalating trial (n=15) were included in this analysis. Thalidomide was administered twice daily. Thirty-two patients (76%) had failed prior therapy and 26 patients (62%) had extrahepatic metastasis diseases. Results: The administration dose of thalidomide was 200 mg/day and 300 - 400 mg/day in 45% and 43% of patients, respectively. The serum a-fetoprotein (AFP) level in 8 out of 28 patients whose baseline value was > 400 ng/mL had a > 50% fall for more than 4 weeks. Partial response (PR) was achieved in 2 (4.9%, 95% CI: -2.0%-11.8%), stable diseases (SD) in 15 (36.6%) and progressive disease (PD) in 24 (58.5%). Mixed tumor response with a significant reduction of total tumor burden for more than 4 weeks was observed in 2 of 15 SD patients. The disease stabilization (PR+SD) rate was neither affected by Child-PughÕs class, A versus B/C, nor by an administration dose of thalidomide, 200 mg/day versus > 300 mg/day. The overall survival time of patients with PR/SD and PD was 291 and 81 days, respectively. Adverse effects mainly consisted of mild constipation, lethargy/drowsiness and skin rash. Conclusion: The data suggests that oral thalidomide has moderate effects in stabilizing the progression of advanced HCC even in the presence of severe underlying liver cirrhosis.

KEY WORDS: hepatocellular carcinoma, angiogenesis inhibitor, thalidomide.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prevention.