***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 This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents BACKGROUND & AIMS Sorafenib , a multi-kinase inhibitor with anti-angiogenic activity , was recently approved for the treatment of advanced hepatocellular carcinoma ( HCC ) .  Metronomic chemotherapy using tegafur/uracil ( 4:1 molar ratio ) , an oral fluoropyrimidine , has been shown to enhance the anti-tumor effect of anti-angiogenic agents in pre clinical models . This phase II study evaluated the efficacy and safety of combining metronomic tegafur/uracil with sorafenib in patients with advanced HCC . METHODS Patients with histologically- or cytologically-proven HCC and Child-Pugh class A liver function were treated with sorafenib ( 400 mg twice daily ) and tegafur/uracil ( 125 mg/m(2 ) based on tegafur twice daily ) continuously as first-line therapy for metastatic or locally advanced disease that could not be treated by loco-regional therapies . The primary endpoint was progression-free survival ( PFS ) . RESULTS The study enrolled 53 patients . Thirty-eight patients ( 72 % ) were hepatitis B surface antigen-positive . The median PFS was 3.7 months ( 95 % C.I. , 1.9 - 5.5 ) and the median overall survival was 7.4 months ( 95 % C.I. , 3.4 - 11.4 ) . According to RECIST criteria , 4 patients ( 8 % ) had a partial response and 26 patients ( 49 % ) had a stable disease . Major grade 3/4 toxicities included fatigue ( 15 % ) , abnormal liver function ( 13 % ) , elevated serum lipase ( 10 % ) h and -foot skin reaction ( HFSR ) ( 9 % ) , and bleeding ( 8 % ) . HFSR was the major adverse event result ing in dose reduction ( 19 % ) or treatment delay ( 21 % ) . CONCLUSIONS Metronomic chemotherapy with tegafur/uracil can be safely combined with sorafenib and shows preliminary activity to improve the efficacy of sorafenib in advanced HCC patients AIM After transarterial chemoembolization ( TACE ) , the residual cancer cells are under extensive hypoxic or even anoxic environment . Hypoxia can lead to adaptive responses . For example , angiogenesis will help these cells survive . In this study , we examined the effect of TACE on angiogenesis and expression of vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( b-FGF ) and to assess their relevance to Walker-256 transplanted hepatoma . METHODS Male Wistar rats were inoculated with Walker-256 tumor in the left lobe of liver .  Angiography and transarterial chemoembolization were performed at d14 after transplantation . Sixty rats bearing walker-256 transplanted hepatoma were r and omly divided into control group , arterial infusion group and TACE group . Each group consisted of twenty rats .  Normal saline , 5-Fu , 5-Fu and lipiodol were infused through hepatic artery respectively . Two weeks after the infusion , staining of factor VIII , VEGF and b-FGF was performed by immunohistochemistry method in routine paraffin-embedded sections . Microvessel density ( MVD ) was counted in endothelial cells with positive factor VIII . Their expression levels were analyzed in conjunction with the pathologic features . RESULTS While a smaller tumor volume was found in TACE group ( F=37.818 , P<0.001 ) , no statistical differences between MVD and expression of VEGF and b-FGF were found among the 3 groups . MVD of the control group , chemotherapy group and chemoemoblization group was 80.84+/-24.24 , 83.05+/-20.29 and 85.20+/-23.91 ( F=0.193 , P=0.873 ) , respectively . The positive expression of VEGF and b-FGF was 75 % , 75 % , 85 % ( chi2=0.449 , P=0.799 ) and 30 % , 25 % , 30 % ( chi2=0.141 , P=0.922 ) , respectively . Statistical analysis revealed a positive correlation between the expression of VEGF and MVD ( r=0.552 , P<0.001 ) . CONCLUSION There has been little influence of lipiodol chemoembolization on the formation of tumor angiogenesis , but the development of neovascularization and expression of VEGF play important roles in establishment of collateral circulation and reconstruction of blood supply of residual cancer tissue Purpose Advanced hepatocellular carcinoma ( HCC ) not eligible for local therapies has limited chances of cure . Sorafenib is a multikinase inhibitor with proven activity in advanced HCC . Octreotide is used in this setting with conflicting results . Treatment with sorafenib and long-acting octreotide was tested in advanced HCC to evaluate safety and activity . Methods Fifty patients with advanced HCC , Child-Pugh A or B , received sorafenib at a dosage of 800 mg/day for 28 days with a following week of rest and long-acting octreotide at a dose of 40 mg , administered every 28 days . Results All patients were assessable for safety and efficacy . Sixteen patients out of 50 ( 34 % ) were naïve from other therapies , while all the others were previously treated with local and /or systemic treatments . We achieved 5 partial responses ( 10 % ) , 33 stable diseases ( 66 % ) and 12 progressions of disease ( 24 % ) . Median time to progression was 7.0 months ( 95 % CI , 3.0–10.9 months ) , and median overall survival was 12 months ( 95 % CI , 6.3–17.4 months ) . Treatment was well tolerated . Diarrhoea ( 6 % ) and hypertension ( 4 % ) were the most frequent grade 3 toxicities . Conclusions Our data suggest that the combination between sorafenib and long-acting octreotide is active and well tolerated in patients with advanced HCC and could represent another efficacious chance for the management of this population BACKGROUND AND AIMS The aim of this study was : ( i ) to define the characteristics of hepatocellular carcinoma ( HCC ) associated with recurrences following initial remission by transcatheter arterial chemoembolization ( TACE )  ; ( ii ) to evaluate the patterns of recurrences ; and ( iii ) find a better surveillance method of detecting recurrent HCC . METHODS Out of 230 consecutive HCC patients who underwent TACE , 77 with initial remission were followed prospect ively for at least 12 months . We compared the recurrence rates according to the characteristics of the tumors and analyzed the locations of the recurrent HCC . The diagnostic efficacies of CT scans with serum AFP , angiography and Lipiodol CT scan in detecting recurrent HCC were also evaluated . RESULTS Recurrent HCC was detected in 40 patients during a median period of 27 months . The recurrence rate of multinodular HCC was higher than the single nodular type . All six patients with portal vein thrombosis recurred . Even though 45 % of recurrences were adjacent to original tumors , 63 % were separated from them ( 8 % at both ) . Hepatocellular carcinoma with heterogeneous Lipiodol uptake tended to recur at the site adjacent to the original tumors more frequently than HCC with homogeneous Lipiodol uptake . Only 18 of 40 recurrent HCC were initially detected by serum alpha-fetoprotein ( AFP ) and CT scans : 19 by angiography and three only by Lipiodol CT scan . CONCLUSION Our data indicated that HCC of the multinodular type and with portal vein thrombosis recur more frequently following initial remission by TACE . It is also suggested that regular angiography in addition to serum AFP and CT scan may be valuable in detecting recurrent HCC . Other treatment modalities may need to be combined to ablate tumors completely and to therefore reduce recurrences , especially in HCC with heterogeneous Lipiodol uptake Sorafenib , an oral multikinase inhibitor , shows efficacy in renal cell and hepatocellular carcinoma ( HCC ) and is well tolerated when combined with doxorubicin in other solid tumours . Eighteen patients with inoperable HCC received doxorubicin 60 mg/m(2 ) IV for up to six 3-week cycles . Sorafenib 400 mg bid was administered continuously starting day 4 . Patients discontinuing doxorubicin were eligible for sorafenib monotherapy . The most frequent grade 3 - 4 drug-related adverse events were neutropaenia ( 61 % ) , leukopaenia ( 45 % ) and diarrhoea ( 17 % , grade 3 ) . Seven of eight patients who completed six cycles of doxorubicin continued treatment with sorafenib for at least 3 months . Doxorubicin  moderately increased AUC ( 21 % ) and C(max ) ( 33 % ) when administered with 
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Conclusions Treatment with sorafenib results in statistically significant , but clinical ly modest , improvements in OS , TTP , and DCR .
For patients with hepatitis B , response seems to be poorer than for those with hepatitis C. The frequency of h and –foot syndrome seems to be higher when sorafenib is used in advanced cirrhosis and is combined with 5-FU drugs .
It is not clear that sorafenib combined with other treatments is more effective than sorafenib alone