Interim analysis of START: Study in asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial

Abstract

Transarterial chemoembolization (TACE) represents a first-line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia-Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5-20 ml) and doxorubicin (30-60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention-to-treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.Hepatocellular carcinoma (HCC) is fifth most common cancer worldwide 1 but has a very uneven geographic distribution. South-east Asian countries and tropical Africa show the highest incidence with peak rates of 150 per 100,000 in Taiwan 2 and 28 per 100,000 in Singapore. 3 Over 600,000 new cases of liver cancer are diagnosed globally each year, 1 and the Asia-Pacific regions contribute more than 50% of these. The lowest rates are found in western countries, Australia,

Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

“…Nagano et al noticed that the overall median progression-free survival (PFS) of advanced HCC was 2.0 months (40). In addition, the association between sorafenib therapy and longer DFS is largely concordant with previous studies in patients with HCC (25,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). In a pilot study by Wang et al (25) that included 31 patients at a high risk of recurrence, sorafenib therapy following hepatic resection significantly improved the time to recurrence as well as the recurrence rate.…”

The Roles of Doxorubicin in Hepatocellular Carcinoma

“…Similar clinical studies are currently being conducted globally [94,95]. It is hoped that the findings from these studies corroborate the positive results obtained from the Asia-Pacific region [93].…”

“…Given the different modes of actions between the kinase inhibitor (sorafenib) and the cytotoxic agent (doxorubicin), it is perfectly reasonable to evaluate the combination of these two classes of drug and assess the clinical benefits that may bring to HCC patients. Excitingly, a recent phase II study revealed the combined use of sorafenib and doxorubicin (administrated as conventional TACE) in patients from the Asia-Pacific region with intermediate HCC [93]. The disease control rate and overall response rate were reported to be 91.2 % and 52.4 %, respectively.…”

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

“…improved survival benefit in patients with stage B disease receiving a combination of sorafenib and transcatheter arterial chemoembolization (TACE) (Chung et al, 2013;Park et al, 2012).…”