Open-Label Single-Arm Phase II Trial of Sorafenib Therapy with Drug-eluting Bead Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma: Clinical Results

Abstract

).q RSNA, 2015 Purpose:To determine the efficacy of combined continuous sorafenib therapy and drug-eluting bead (DEB) transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Materials andMethods:This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Inclusion criteria included unresectable HCC, a treatment naïve status, an Eastern Cooperative Oncology Group score of 0-1, and a Child-Pugh score of A-B7. Continuous sorafenib therapy (400 mg twice daily) was started 1 week before the first round of DEB TACE, which was performed in 6-week cycles. Up to four rounds of DEB TACE therapy were allowed on demand within 6 months. The primary end point was safety. Secondary end points were time to progression (TTP), response rate, and overall survival (OS) and were stratified by the Barcelona Clinic Liver Cancer (BCLC) stage and the duration of sorafenib therapy. OS was assessed with Kaplan-Meier estimates, and the Mantel-Cox log-rank test was used to determine differences in survival. A two-sided P value of less than .05 was considered to indicate a significant difference. Results:Fifty patients-of whom 76% were male, 92% had a ChildPugh score of A, and 62% had BCLC stage C disease-underwent a median of three cycles of therapy. The 6-month disease control rate (defined as complete response plus partial response plus stable disease) was 94% according to the response evaluation criteria in solid tumors. Median TTP and OS were 13.9 and 20.4 months, respectively, and 81% of toxicities were grades 1-2. There was one death that was possibly treatment related. Conclusion:Combined continuous sorafenib therapy and on-demand DEB TACE provided excellent local disease control and did not lead to multiplicative toxicities. Long-term administration of sorafenib therapy in combination with DEB TACE may have a survival benefit in patients with advanced HCC.q RSNA, 2015

Adjuvant Medications That Improve Survival after Locoregional Therapy

“…A randomized trial showed that oral ginsenoside Rg3, a ginseng extract with anti-inflammatory and anti-angiogenic effects, improved survival after transarterial chemoembolization (TACE) of HCC (7). Sorafenib, an oral anti-angiogenesis agent, might improve survival after TACE of advanced HCC (4, 8). Bumetanide, a diuretic that also inhibits glycolysis, increased tumor necrosis after transarterial embolization (TAE) of HCC in an animal model (9).…”

Early sorafenib‐related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients

“…With the important exception of the recently introduced multi‐kinase inhibitor sorafenib, systemic chemotherapies and other molecularly targeted therapies have offered no survival benefit . Transarterial chemoembolization (TACE) is the standard treatment for intermediate‐stage HCC . In a 2002 trial in Spain, a significant improvement in survival was achieved with TACE compared to best supportive care ( p = 0.009) .…”

mRECIST response combined with sorafenib‐related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib

“…Currently, the clinical outcomes reported in studies evaluating the efficacy of TACE‐S are widely varied . Furthermore, the significant differences found in these studies can be attributed to ignorance of the response to therapy.…”

“…Therefore, TACE‐S may be the alternative choice of treatment for patients with unresectable HCC . Indeed, a series of studies have reported the survival benefit conferred by TACE‐S for HCC …”