Thalidomide in Advanced Hepatocellular Carcinoma with Optional Low-Dose Interferon-α2a upon Progression

Abstract

Learning Objectives: After completing this course, the reader will be able to: Identify the etiologic factors contributing to the increasing incidence of hepatocellular carcinoma in the U.S.Explain the rationale for antiangiogenic therapeutic strategies in the treatment of hepatocellular carcinoma.Describe the clinical features associated with a particularly poor prognosis in unresectable hepatocellular carcinoma. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Purpose. To evaluate thalidomide in advanced hepatocellular carcinoma (HCC) and to evaluate combined thalidomide and low-dose interferon-α2a (IFN-α2a) 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-α2a. 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-α2a; 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-α2a is neither safe nor efficacious in this population.