***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 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 Background Disease progression of hepatocellular cancer ( HCC ) in patients eligible for liver transplantation ( LTx ) occurs in up to 50 % of patients , result ing in withdrawal from the LTx waiting list . Transarterial chemoembolization ( TACE ) is used as bridging therapy with highly variable response rates . The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer . Design The HeiLivCa study is a double-blinded , controlled , prospect i ve , r and omized multi-centre phase III trial . Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid . Patients in study arm B will be treated with transarterial chemoembolization plus placebo .  A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled . An interim patients ' analysis will be performed after 60 events . Evaluation of time-to-progression as primary endpoint ( TTP ) will be performed at 120 events . Secondary endpoints are number of patients reaching LTx , disease control rates , OS , progression free survival , quality of live , toxicity and safety . Discussion As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities . This study is design ed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx LBA154^ Background : The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients ( pts ) with intermediate-stage HCC ( BCLC B ) . METHODS Pts were eligible if they had asymptomatic , unresectable , multinodular tumors without vascular invasion ( VI ) or extrahepatic spread ( EHS ) ; Child-Pugh A liver functional status ; and ECOG PS 0 . Pts were r and omized to receive S 400 mg bid or matching P continuously ( 1 cycle = 4 wks ) until progression . All pts received TACE with DEBDOX ( 150 mg doxorubicin ; Biocompatibles UK Ltd ) 3 - 7d after first dose of study drug , and then on d1 ( ±4d ) of months 3 , 7 , and 13 , and q6 months thereafter . The primary endpoint was time to radiologic progression ( TTP ) by independent review ( predefined alpha = 0.15 ) . Secondary endpoints were overall survival ( OS ) , time to VI/EHS , time to untreatable progression ( TTUP ) , and safety . RESULTS Of 452 pts screened , 307 were r and omized to S ( n=154 ) or P ( n=153 ) . The HR for TTP was 0.797 ( 95 % CI , 0.588 , 1.080 ; p=0.072 ) . Median TTP ( 50th percentile ) was 169d/166d in the S and P groups , respectively ; TTP at the 25th and 75th percentiles ( preplanned ) was 112/88d and 285/224d in the S and P groups , respectively . There were no unexpected safety findings . Median treatment duration in the S and P groups was 4.8 and 6.3 months , respectively , and median daily dose of study drug was 566 mg and 791 mg , respectively . CONCLUSIONS The study met its primary endpoint of improving TTP when S was added to a regimen of TACE with DEBDOX , compared with TACE with DEBDOX alone . The combination was well tolerated ; no new safety findings that would preclude use of the combination were observed . The encouraging efficacy signal requires confirmation with data from ongoing phase III trials evaluating the combination of S plus TACE . [ Table : see text ] 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 chemother 
    Output:
    
The common toxicities included fatigue , diarrhea , nausea , h and foot skin reaction ( HFSR ) , hematological events , hepatotoxicity , alopecia , hepatotoxicity , hypertension and rash/desquamation .
AEs are generally manageable with dose reductions .
Combination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS .