This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, A. X. Articles by Ryan, D. P. Search for Related Content PubMed PubMed Citation Articles by Zhu, A. X. Articles by Ryan, D. P.

A Phase II Study of Epirubicin and Thalidomide in Unresectable or Metastatic Hepatocellular Carcinoma

Massachusetts General Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Correspondence: Andrew X. Zhu, M.D., Massachusetts General Hospital Cancer Center, 100 Blossom Street, Cox 640, Boston, Massachusetts 02114, USA. Telephone: 617-724-0786; Fax: 617-724-3166; e-mail: azhu{at}partners.org

Background. The median survival time for patients with unresectable hepatocellular carcinoma (HCC) is <6 months, and no effective standard systemic chemotherapy is available. Both epirubicin (Ellence^®; Pfizer Pharmaceuticals, New York, NY, http://www.pfizer.com) and thalidomide (Thalomid^®; Celgene Corporation, Warren, NJ, http://www.celgene.com) have reported activity for HCC as single agents, and they have different mechanisms of action and nonoverlapping toxicities. Therefore, we performed a phase II study using the combination of epirubicin and thalidomide in patients with unresectable and metastatic HCC.

Methods. Nineteen patients with measurable, unresectable, or metastatic HCC were enrolled. All patients were required to have adequate major organ function and performance status. The treatment consisted of weekly epirubicin at a dose of 20 mg/m² administered i.v. and daily thalidomide at a dose of 200 mg orally given as a 3-weeks-on/1-week-off schedule. Intrapatient dose escalation of thalidomide was allowed every 2 weeks up to 800 mg daily as long as tolerated. Physical examinations, toxicity assessments, and serum chemistry analyses were performed weekly, and tumor measurements were conducted every 8 weeks.

Results. All 19 patients enrolled into the study were evaluable for toxicity assessment and 17 patients were evaluable for response assessment. A total of 71 cycles of chemotherapy was administered, with a median of two cycles administered to each patient (range 1–14). No complete or partial responses were observed. Seven patients (41%) had stable disease, with a median duration of 6 months (range 5–14). The median survival time for all 19 patients was 196 days (95% confidence interval 93–302). The treatment was generally well tolerated. Treatment-related toxicities included constipation (grade 3, 5%; grade 2, 37%; grade 1, 21%), fatigue (grade 3, 5%; grade 2, 42%), and sensory neuropathy (grade 2, 5%; grade 1, 32%). Four patients required dose reductions of thalidomide due to treatment-related toxicities, and the median tolerated dose of thalidomide was 200 mg daily.

Conclusions. The combination of epirubicin and thalidomide was well tolerated when administered in the schedule used in this study. This regimen has limited activity in HCC, with some patients achieving stable disease and clinical benefit. There is a need for defining more effective systemic therapies for HCC.

Key Words. Hepatocellular carcinoma • Epirubicin • Thalidomide • Angiogenesis • Clinical study

This article has been cited by other articles:

				S. R. Vora, H. Zheng, Z. K. Stadler, C. S. Fuchs, and A. X. Zhu Serum {alpha}-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma Oncologist, July 1, 2009; 14(7): 717 - 725. [Abstract] [Full Text] [PDF]

				A. X. Zhu Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be? Oncologist, July 1, 2006; 11(7): 790 - 800. [Abstract] [Full Text] [PDF]

				A. X. Zhu, L. S. Blaszkowsky, D. P. Ryan, J. W. Clark, A. Muzikansky, K. Horgan, S. Sheehan, K. E. Hale, P. C. Enzinger, P. Bhargava, et al. Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma J. Clin. Oncol., April 20, 2006; 24(12): 1898 - 1903. [Abstract] [Full Text] [PDF]

				C.-C. Lee, Y.-H. Wu, S.-H. Chung, and W.-J. Chen Acute Tumor Lysis Syndrome After Thalidomide Therapy in Advanced Hepatocellular Carcinoma Oncologist, January 1, 2006; 11(1): 87 - 88. [Full Text] [PDF]