Phase I/II study of sorafenib in combination with intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable advanced hepatocellular carcinoma with portal vein tumor thrombus.

Abstract

441 Background: Our purpose in the study was to ascertain the feasibility of a combination therapy with sorafenib and hepatic arterial infusion therapy (HAIC) using cisplatin (CDDP) for unresectable advanced HCC included portal vein tumor thrombus. Methods: Phase I study: Soraenib was administered continuously, whereas CDDP was given on day1, 8, and 15. The dose of sorafenib was escalated in two steps from 400 to 800 mg/body, whereas the dose of CDDP was escalated in three steps from 20 to 25 and 30 mg/m2. We estimate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of this therapy, to determine the recommended dose (RD). Phase II study: Thirty-five patients with unresectable HCC received this therapy under RD, and the efficacy and safety were assessed. Results: Phase I study: 15 patients (11 male/4 female, median age: 73.1 years) with unresectable advanced HCC have been enrolled. None of the patients treated with sorafenib 400mg and cisplatin 20 mg/m2 experienced DLT. Three of three patients treatd with sorafenib 800mg and cisplatin 20 mg/m2 experienced DLTs (two serum bilirubin elevation and one hepatic encephalopathy). None of the patients treated with sorafenib 400mg and cisplatin 25 mg/m2 experienced DLT. One of six patients treated with sorafenib 400mg and cisplatin 30 mg/m2 experienced dose-limiting thrombocytopenia, and One of them experienced dose-limiting serum aspartate aminotransferase elevation. Phase II study: 35 patients (27 male / 8 female, median age : 69.2 years) with unresectable advanced HCC have been enrolled. The clinical response were rated as 9 partial response (PR), 18 stable disease (SD), and 8 progressive disease (PD). Conclusions: In this study, RD of this therapy was sorafenib 400mg/body and CDDP 30 mg/m2. Sorafenib in combination with intermittent HAIC using CDDP for unresectable advanced HCC was expected to be safe and effective treatment. Clinical trial information: 000008571.