***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC  is well tolerated and safe , with most toxicities  related to sorafenib  . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising BACKGROUND / AIMS Lipiodol chemoembolization is a widely used method of treatment in patients with unresectable hepatocellular carcinoma , but its efficacy is still debated . The aim of our study was to assess the efficacy of lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma . METHODS Seventy-three patients with unresectable hepatocellular carcinoma , but without severe liver disease or portal vein occlusion , were r and omly assigned to receive either repeated lipiodol chemoembolization ( lipiodol , cisplatin ( 2 mg/kg ) , lecithin , and gelatin sponge injected into the hepatic artery ) plus tamoxifen ( 40 mg ) or tamoxifen alone . The main end-point was survival . RESULTS The 37 patients in the lipiodol chemoembolization group received 104 courses ( median 3 per patient ) . By 1 September 1996 , 58 patients had died : 30 in the lipiodol chemoembolization group and 28 in the tamoxifen group . There was no difference in survival between the two groups ( p=0.77 ) . The relative risk of death in the lipiodol chemoembolization plus tamoxifen group as compared to the tamoxifen group was 0.92 ( 95 % confidence interval 0.55 to 1.56 ) . At 1 year , survival was 51 % and 55 % , respectively . An objective tumoral response was more frequently observed in the lipiodol chemoembolization group than in the tamoxifen group ( 24 versus 5.5 % , respectively , p=0.046 ) . Lipiodol chemoembolization caused two deaths and induced signs of liver failure in 51 % of the patients assigned to this treatment . CONCLUSION In our r and omized study , lipiodol chemoembolization did not improve the survival of patients with unresectable hepatocellular carcinoma treated with tamoxifen BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) .  Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) .  HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses Abstract Objectives To investigate the safety of transarterial chemoembolisation ( TACE ) in combination with sorafenib in patients with hepatocellular carcinoma ( HCC ) . Methods Patients with Child – Pugh A/B liver function , ECOG performance status 0–2 and HCC treatable with TACE received continuous sorafenib 800 mg/day , and TACE with doxorubicin ( 75 , 50 and 25 mg/m2 according to serum bilirubin : < 1.5 , 1.5–3 , and > 3 mg/dL ) and lipiodol 2 weeks after sorafenib initiation and repeated every 4 weeks . Results Fifteen patients were included ( Child – Pugh A/B , n = 12/3 ; Barcelona Clinic Liver Cancer-A/B/C , n = 1/9/5 ; ECOG 0/2 , n = 14/1 ) . Median time on sorafenib was 5.2 months ( 2.6–7.4 months ) ; median number of TACE sessions was 3 . Common adverse events were abdominal pain ( n = 14 ) , weight loss ( n = 13 ) , alopecia ( n = 12 ) , fatigue ( n = 12 ) and hyperbilirubinaemia ( n = 11 ) . There were 32 serious adverse events ( grade ≥3 ) ; 9/10-unscheduled hospital admissions and 4/5 deaths were considered TACE-related . The study was stopped prematurely because of safety concerns . At 6 months , 2 and 5 patients had complete or partial responses ; 1 had stable disease . Median overall survival was 10.6 months ( 95 % CI : 5.2–16 months ) . Conclusion These findings do not support use of an intensive , high-dose doxorubicin-based TACE regimen in combination with sorafenib in this study population .Key Points• Transarterial chemoembolisation ( TACE ) is widely used in patients with hepatocellular carcinoma ( HCC ) • Various antiangiogenic and other agents have been used to augment this treatment • We tested lipiodol-TACE with bilirubin-adjusted doxorubicin dosing in combination with sorafenib • This trial was stopped prematurely because of safety reasons • Our safety results do not support the combination of sorafenib with this TACE BACKGROUND & AIMS Transarterial chemoembolization ( TACE ) is an important palliative treatment for unresectable hepatocellular carcinoma ( HCC ) , but TACE-induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis . The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC . METHODS The primary objectives of this prospect i ve , single-arm , phase II study were to evaluate safety and time to progression ( TTP ) .  Sorafenib was given 3 days after TACE and was administered for up to 24 weeks . Repeated TACE was performed on dem and . Tumor response was assessed every 8 weeks . RESULTS Fifty patients were treated and followed from July 2009 to May 2011 . All patients were in Barcelona Clinic Liver Cancer ( BCLC ) stage B ( 82 % ) or C ( 18 % ) . The median time of follow-up was 14.9 months and a median of 1 TACE session was given ( range , 1 - 4 ) . The median dose intensity of sorafenib  was 68.7 % ( range , 37.3 - 100 ) of 800 mg daily . The most common reasons for dose reduction were h and -foot syndrome and thrombocytopenia .  Thirty patients completed the study and 17 patients discontinued sorafenib due to disease progression . The overall median TTP was 7.1 months ( 95 % confidence interval ( CI ) , 4.8 - 7.5 months ) : 7.3 months in BCLC stage B ; 5.0 months in BCLC stage C. The 6-month progression-free survival rate was 52 % ( 95 % CI , 37.3 - 66.1 ) . CONCLUSIONS Concurrent treatment of unresectable HCC with conventional TACE and sorafenib demonstrates a manageable safety profile and a possibility of promising efficacy This prospect i ve non‐r and omized controlled trial aim ed to compare the efficacy of sorafenib in combination with transarterial chemoembolization ( TACE ) vs TACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma 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 prospect i ve 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 clinical ly 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 . Clinical ly , 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 BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group 
    Output:
    
Frequently reported grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase , fatigue , hypertension , h and -foot skin reaction and diarrhea .
Conclusions The sorafenib/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate stage/advanced HCC .
The reported efficacy of a sorafenib/TACE combination appears to compare favorably with sorafenib or TACE monotherapies , the most commonly implemented strategies for unresectable HCC .