An interim analysis of a phase II study of the combination of TACE and sorafenib in patients with unresectable hepatocellular carcinoma in National Cancer Center Korea (COTSUN KOREA, NCT00919009).

Abstract

253 Background: Transarterial chemoembolization (TACE) is the palliative treatment for patients with unresectable HCC. TACE-induced ischemic injury is known to increase circulating VEGF and related with poor prognosis.The aim of this study is to evaluate efficacy and safety of combined TACE with sorafenib, VEGFR inhibitor in unresectable HCC patients. Methods: This study is a non-randomized, open-labeld, single-arm, phase II investigator-initiated clinical study. Estimated number of subjects was 50 under the assumption of 3.2 months of median time to progression (TTP) with TACE alone. All patients are Child-Pugh class A or superb B. Sorafenib begins to be administered on 3 days after the first session of TACE and will be subsequently administered up to 24 weeks. Efficacy of TACE was evaluated after 4 weeks from TACE by dynamic CT. Repeated TACE is performed “on demand” in case of PR or SD according to CT/MRI evaluation. Results: A total of 50 patients were enrolled for this interim analysis. Male was 84% and mean age was 61.5years. Causes of underlying chronic liver disease were HBV in 28 patients (65.1%). Patients were categorized into modified UICC stage II (15, 30.0%), III (24, 48.0%) and IVA (11, 22.0%). Median follow-up period was 5.3 months (range, 1.0–13.1). The size of index lesions was ranged from 1.0 cm to 13.1 cm, and number of lesions was between 1 and 5. Number of TACE sessions was 1.0 (range, 1–4). Common adverse events (AE) during sorafenib therapy were elevation of serum AST/ALT (96.8%), hypocalcemia (90.0%), thrombocytopenia (84.0%), and hyperbilirubinemia (76.0%). Hand-foot skin reaction was most frequently observed among AE of NCI CTCAE grade 3 or higher (40.0%), followed by elevation of serum ALT (38.0%). Dose reduction of sorafenib was needed most commonly due to hand-food skin reaction (n=29). Median TTP was 5.1 months (range, 3.8–6.3). Conclusions: Adverse events were approved as acceptable by independent monitoring system. Preliminary evidence of antitumor activity was also observed. This trial can be safely performed with close monitoring in inoperable and/or unresectable HCC patients. No significant financial relationships to disclose.

Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma

“…For example, switch to sorafenib might be a reasonable measure in patients with intermediate‐stage HCC who are not eligible for, or progressed after TACE 16 . The combination of TACE plus sorafenib might also be a suitable alternative to protect against tumor progression due to ischemic injury following TACE; 17–19 this strategy is supported by recent preliminary results of a prospective study which reported prolonged TTP 20 . The need for evaluation of the outcome of combined TACE and systemic therapy in HCC patients has recently been given high priority 21 …”

“…16 The combination of TACE plus sorafenib might also be a suitable alternative to protect against tumor progression due to ischemic injury following TACE; [17][18][19] this strategy is supported by recent preliminary results of a prospective study which reported prolonged TTP. 20 The need for evaluation of the outcome of combined TACE and systemic therapy in HCC patients has recently been given high priority. 21 The aim of this study was to identify factors associated with TACE refractoriness.…”

Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review

“…The median TTP was 6 months. A phase II study of the combination of TACE and sorafenib in patients with unresectable HCC showed that the median TTP was 5.1 months [ 19 ]. Hu et al compared TACE plus sorafenib with TACE alone in Barcelona Clinic Liver Cancer stage C patients, and the TTP was longer in the combined group (2.6 months vs .…”