Imatinib treatment for patients with advanced stage hepatocellular carcinoma: A multicenter phase II trial.

Abstract

e14629 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with limited treatment options in advanced stages. The antitumor activity of systemic chemotherapies in patients with HCC has been disappointing. The aim of this study was to evaluate the safety and efficacy of imatinib, a tyrosine kinase inhibitor, in patients with advanced HCC. Methods: Patients with stage III and IVa/b HCCs without surgical and/or loco ablative therapeutic options and preserved liver function (CPC A/B) were eligible. The patients were treated with 400 mg imatinib daily for 12 months. Response was assessed by CT scan. Results: 22 patients (5 f, 16 m; mean age 67) were enrolled in this study. The causes of liver disease were mainly viral (5) and (non) alcoholic fatty liver disease (8). 15 patients presented with CPC A and 3 with B, 3 patients had no evidence of liver cirrhosis. 14 patients had had previous HCC-treatments, mainly resection or loco ablative therapies. Patients were treated with imatinib for a median time period of 9 (4-52) weeks; in 10 patients imatinib was discontinued due to tumor progression, in 4 due to the patients' decision, in 2 due to decompensated liver cirrhosis and in one due to pruritus; 4 patients received the drug for the intended 12 months. Median TTP was 12 (95%CI: 10-14) weeks. Two patients (HCC in noncirrhotic liver) had stable disease throughout the study period, one until discontinuation (pruritus) and the remaining 18 patients developed disease progression. The median overall survival was 7.4 (95%CI: 5.9-8.9) months. Complications due to decompensated liver cirrhosis were the causes of death in all patients. No severe adverse event related to imatinib was observed; the most common adverse events were nausea (10) and peripheral edema (8). In 4 patients imatinib dosage had to be reduced to 200 mg daily after 2, 4, 14 and 28 weeks of treatment because of nausea (3) and angioedema (1). Conclusions: The results of this multicenter study suggest that imatinib is well tolerated in the majority of HCC patients. The median TTP was 11 weeks which is comparable to other targeted therapies indicating that imatinib might be a promising candidate for further studies in the treatment of advanced HCC. No significant financial relationships to disclose.