The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma

Abstract

BackgroundThe long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC.MethodsBetween June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded.ResultsThe median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed.ConclusionTACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma

“…The HR in sorafenib/placebo for overall survival was 1.06 (95%CI: 0.69-1.64; P = 0.790) and they concluded that combination therapy with TACE + sorafenib is not superior to TACE alone [35] . However, our findings are in contrast with those from a recent study assessing the effectiveness of TACE + sorafenib vs TACE in Chinese patients; Qu et al [30] reported a statistically significant improvement in median survival time with the combination therapy when compared to TACE alone (27 mo vs 17 mo, P = 0.001). The primary reason for the positive results observed in the study by Qu et al [30] may be attributed to their larger sample size (90 patients) in their study compared with our study with 43 patients.…”

“…Furthermore, the study by Qu et al [30] is limited by a relatively uneven duration of patient follow-up for the compared treatment modalities (25 mo for TACE alone and 46 mo for combination therapy). In contrast, our study has even and longer duration of follow-up (56 mo for TACE alone and 52 mo for combination therapy).…”

“…A recently published retrospective observational study by Qu et al [30] conducted in China showed that median survival time was significantly longer in patients with HCC treated with sorafenib and TACE vs TACE alone (27 mo vs 17 mo, P = 0.001). Despite the positive outcomes reported with the combined therapy, a clinical trial that enrolled a small number of patients was stopped prematurely due to adverse events (AE) and safety concerns with the combination therapy of high-dose doxorubicinbased TACE regimen and sorafenib [31] .…”

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

“…The combination of the (doxorubicin-loaded) spheres with systemic anti-angiogenic therapy has already been reported (9)(10)(11), and several phase II and III trials with oral sunitinib (SATURNE) or sorafenib are under way or completed (12,13). Sunitinib malate (SU11248) is available as an oral formulation from Pfizer (New York, New York) and was approved by the U.S. Food and Drug Administration in 2006 for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor (14).…”

Recent advances in multidisciplinary management of hepatocellular carcinoma

“…In phase Ⅱ studies, sorafenib concomitant with TACE or DEB-TACE was well tolerated and effective in unresectable HCC [148][149][150][151] . Synchronous therapy with sorafenib and TACE has also been retrospectively analyzed: the median overall survival for the combined sorafenib and TACE was 27 mo compared to 17 mo for TACE alone [152] . Several prospective controlled studies have evaluated the efficacy of combination treatment [153][154][155][156][157][158] (Table 2).…”