***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 PURPOSE Open-label , phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer . PATIENTS AND METHODS Patients were stratified and r and omly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day . Primary end point was overall survival ( OS ) . RESULTS Early trial termination occurred for futility and safety reasons . A total of 1,074 patients were r and omly assigned to the study ( sunitinib arm , n = 530 ; sorafenib arm , n = 544 ) . For sunitinib and sorafenib , respectively , median OS was 7.9 versus 10.2 months ( hazard ratio [ HR ] , 1.30 ; one-sided P = .9990 ; two-sided P = .0014 ) ; median progression-free survival ( PFS ; 3.6 v 3.0 months ; HR , 1.13 ; one-sided P = .8785 ; two-sided P = .2286 ) and time to progression ( TTP ; 4.1 v 3.8 months ; HR , 1.13 ; one-sided P = .8312 ; two-sided P = .3082 ) were comparable . Median OS was similar among Asian ( 7.7 v 8.8 months ; HR , 1.21 ; one-sided P = .9829 ) and hepatitis B-infected patients ( 7.6 v 8.0 months ; HR , 1.10 ; one-sided P = .8286 ) , but was shorter with sunitinib in hepatitis C-infected patients ( 9.2 v 17.6 months ; HR , 1.52 ; one-sided P = .9835 ) . Sunitinib was associated with more frequent and severe adverse events ( AEs ) than sorafenib . Common grade 3/4 AEs were thrombocytopenia ( 29.7 % ) and neutropenia ( 25.7 % ) for sunitinib ; h and -foot syndrome ( 21.2 % ) for sorafenib . Discontinuations owing to AEs were similar ( sunitinib , 13.3 % ; sorafenib , 12.7 % ) . CONCLUSION OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib . OS was comparable in Asian and hepatitis B-infected patients . OS was superior in hepatitis C-infected patients who received sorafenib . Sunitinib-treated patients reported more frequent and severe toxicity Objective : A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma ( HCC ) patients , and to investigate clinical and molecular predictors of outcome . Methods : 59 patients with advanced HCC received 10 mg/kg i.v . of bevacizumab every 14 days and 150 mg p.o . of erlotinib daily . The primary endpoint was progression-free survival ( PFS ) at 16 weeks . Clinical characteristics and plasma biomarkers expression levels were analyzed . Results : PFS at 16 weeks was 64 % ( 95 % CI 51–76 ) : 14 patients achieved partial response ( 24 % ) , 33 had stable disease ( 56 % ) , 6 progressed ( 10 % ) , and 6 were not evaluable ( 10 % ) . Median overall survival was 13.7 months ( 95 % CI 9.6–19.7 ) , and median PFS was 7.2 months ( 95 % CI 5.6–8.3 ) . Grade 3–4 adverse events included fatigue ( 30 % ) , diarrhea ( 17 % ) , hypertension ( 14 % ) , elevated transaminases ( 12 % ) , and gastrointestinal hemorrhage ( 10 % ) . High plasma angiopoietin-2 , epidermal growth factor receptor , and endothelin-1 , and lack of acneiform rash were associated with poor outcome . Conclusions : The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC . Current correlatives may help to guide future HCC studies This r and omized , controlled trial assessed the efficacy of transarterial Lipiodol ( Lipiodol Ultrafluide , Laboratoire Guerbet , Aulnay-Sous-Bois , France ) chemoembolization in patients with unresectable hepatocellular carcinoma . From March 1996 to October 1997 , 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and r and omly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery ( chemoembolization group , 40 patients ) or symptomatic treatment ( control group , 40 patients ) . One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis . Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease . Survival was the main end point . The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 ( range , 1 - 15 ) courses per patient . Chemoembolization result ed in a marked tumor response , and the actuarial survival was significantly better in the chemoembolization group ( 1 year , 57 % ; 2 years , 31 % ; 3 years , 26 % ) than in the control group ( 1 year , 32 % ; 2 years , 11 % ; 3 years , 3 % ; P = .002 ) . When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model , the survival benefit of chemoembolization remained significant ( relative risk of death , 0.49 ; 95 % CI , 0.29 - 0.81 ; P = .006 ) . Although death from liver failure was more frequent in patients who received chemoembolization , the liver functions of the survivors were not significantly different . In conclusion , in Asian patients with unresectable hepatocellular carcinoma , transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment Purpose : Vali date d biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma ( HCC ) . One of the objectives of the phase III , r and omized , controlled Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy . Experimental Design : In SHARP , 602 patients with advanced HCC were r and omized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis . Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment . The c and i date biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib . Results : In both the entire patient population and the placebo cohort , baseline angiopoietin 2 ( Ang2 ) and VEGF concentrations independently predicted survival . Clinical variables such as macroscopic vascular invasion , Eastern Cooperative Oncology Group ( ECOG ) performance status , and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups . In the sorafenib cohort , trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline ( P of interaction = 0.081 and 0.073 , respectively ) . Conclusions : The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC . In contrast , none of the biomarkers tested significantly predicted response to sorafenib . Clin Cancer Res ; 18(8 ) ; 2290–300 . © 2012 AACR UNLABELLED Angiogenesis inhibition by the vascular endothelial growth factor receptor ( VEGFR ) and platelet-derived growth factor receptor ( PDGFR ) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma ( HCC ) ; however , angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor ( FGFR ) pathway activation . In addition to VEGFR and PDGFR , dovitinib inhibits FGFR . Frontline oral dovitinib ( 500 mg/day , 5 days on , 2 days off ; n = 82 ) versus sorafenib ( 400 mg twice daily ; n = 83 ) was evaluated in an open-label , r and omized phase 2 study of Asian-Pacific patients with advanced HCC . The primary and key secondary endpoints were overall survival ( OS ) and time to tumor progression ( TTP ) as determined by a local investigator , respectively . Patients included in the study were ineligible for surgical and /or locoregional therapies or had disease progression after receiving these therapies . The median OS ( 95 % confidence interval [ CI ] ) was 8.0 ( 6.6 - 9.1 ) months for dovitinib and 8.4 ( 5.4 - 11.3 ) months for sorafenib . The median TTP ( 95 % CI ) per investigator assessment was 4.1 ( 2.8 - 4.2 ) months and 4.1 ( 2.8 - 4.3 ) months for dovitinib and sorafenib , respectively . Common any-cause adverse events included diarrhea ( 62 % ) , decreased appetite ( 43 % ) , nausea ( 41 % ) , vomiting ( 41 % ) , fatigue ( 35 % ) , rash ( 34 % ) , and pyrexia ( 30 % ) for dovitinib and palmar-plantar erythrodysesthesia syndrome ( 66 % ) and decreased appetite ( 31 % ) for sorafenib . Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 ( sVEGFR1 ) and hepatocyte growth factor ( HGF ) below median levels versus at or above the median levels ( median OS [ 95 % CI ] : sVEGFR1 , 11.2 [ 9.0 - 13.8 ] and 5.7 [ 4.3 - 7.0 ] months , respectively [ P = .0002 ] ; HGF , 11.2 [ 8.9 - 13.8 ] and 5.9 [ 5.0 - 7.6 ] months , respectively [ P = 0.0002 ] ) . CONCLUSION Dovitinib was well tolerated , but activity was not greater than sorafenib as a frontline systemic therapy for HCC . Based on these data , no subsequent phase 3 study has been planned . ( Hepatology 2 
    Output:
    
In first-line therapy , patients receiving sorafenib had increased overall survival and progression free survival .