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Thalidomide in Advanced Hepatocellular Carcinoma with Optional Low-Dose Interferon-2a upon Progression

^a Departments of Medicine and Surgery, Mount Sinai School of Medicine, New York, New York, USA; ^b Department of Medicine, New York University School of Medicine, New York, New York, USA

Key Words. Hepatocellular carcinoma • Liver neoplasms • Thalidomide • Interferon-alpha • Hepatitis C virus • Angiogenesis inhibitors

Correspondence: Jonathan D. Schwartz, M.D., Mount Sinai School of Medicine, Hematology-Oncology, One Gustave L. Levy Place, Box 1129, New York, New York 10029, USA. Telephone: 212-241-3984; Fax: 212-876-5276; e-mail: jonathan.schwartz{at}mssm.edu

Purpose. To evaluate thalidomide in advanced hepatocellular carcinoma (HCC) and to evaluate combined thalidomide and low-dose interferon-2a (IFN-2a) after tumor progression on thalidomide. Systemic therapy is minimally effective in HCC and tumor angiogenesis is a potential therapeutic target.

Patients and Methods. Patients with unresectable HCC were eligible if they had preserved hepatic and renal function. The initial thalidomide dosage was 200 mg daily and was adjusted for toxicity. Upon progression, patients could continue thalidomide with additional low-dosage (one million units twice daily) IFN-2a.

Results. Thirty-eight enrolled patients were predominantly hepatitis C virus infected (53%), Child-Pugh class A (79%), and Eastern Cooperative Oncology Group performance status 0–1 (92%); 60% had extrahepatic metastasis. Confirmed disease control was seen in seven patients (18%) and included one complete and one partial response (5% response rate). The median progression-free survival was 2.1 months, and median overall survival was 5.5 months. Tumor invasion of the portal vein or vena cava, large (>10 cm) tumor, and younger age were associated with shorter overall survival. Toxicity included fatigue in 74% of patients. Six patients stopped therapy because of side effects, including two patients (5%) with grade 4 arteriothrombotic events. Five patients continued thalidomide upon progression with the addition of IFN-2a; there was no disease control and 80% had grade 3 toxicity.

Conclusions. Thalidomide is not well tolerated and confers limited disease control in advanced HCC. Combination thalidomide and low-dose IFN-2a is neither safe nor efficacious in this population.

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