***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 Objective : This study was performed to identify clinical predictors for better survival in patients with advanced hepatocellular carcinoma ( HCC ) under sorafenib treatment . Methods : Between December 2007 and January 2010 , 46 patients with advanced HCC were treated with sorafenib until significant tumor progression or intolerable toxicity . We prospect ively collected clinical baseline data as well as data on the incidence and severity of toxic side effects of sorafenib to be correlated with progression-free survival and overall survival ( OS ) , respectively . Results : Only 26.1 % ( n = 12 ) of patients tolerated sorafenib without requiring dose reduction . The most frequent grade 3 toxicities were diarrhea ( 32.6 % ) , h and -foot skin reaction ( 13.0 % ) , fatigue ( 4.3 % ) , and nausea/vomiting ( 2.2 % ) . Eastern Cooperative Oncology Group performance status ( p = 0.034 ) and portal vein infiltration ( p = 0.021 ) significantly correlated with OS . Furthermore , we found a significant correlation between OS and appearance of grade 2 or 3 diarrhea with a median actuarial survival of 11.8 months ( 95 % CI 6.9–16.6 ) compared to 4.2 months in patients with grade 0 or 1 diarrhea ( 95 % CI 0.0–9.1 ; p = 0.009 ) . In contrast , appearance of h and -foot skin reaction did neither correlate with progression-free survival nor with OS . Conclusion : Appearance of grade 2 or 3 diarrhea indicates a better OS of HCC patients undergoing sorafenib treatment BACKGROUND & AIMS Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and , by measuring organ damage and tumor stage , can influence treatment . Moreover , elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma . We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , and bilirubin ; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment . METHODS Patients ( n=602 ) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase ( not significantly elevated , mildly elevated , or moderately elevated ) , alpha-fetoprotein ( normal or elevated ) , and bilirubin ( normal or elevated ) . Bilirubin was measured at baseline and on day 1 of each cycle . RESULTS Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin had shorter overall survival ( OS ) than those with normal baseline concentrations , irrespective of treatment group . No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin . Median changes from baseline in bilirubin concentration at the last cycle of treatment were + 0.17 and + 0.19 mg/dl in the sorafenib and placebo groups , respectively . CONCLUSIONS These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma , irrespective of baseline alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy Purpose : Hypertension is a mechanism-based toxicity of sorafenib and other cancer therapeutics that inhibit the vascular endothelial growth factor ( VEGF ) signaling pathway . This prospect i ve , single-center , cohort study characterized ambulatory blood pressure monitoring as an early pharmacodynamic biomarker of VEGF signaling pathway inhibition by sorafenib . Experimental Design : Fifty-four normotensive advanced cancer patients underwent 24-hour ambulatory blood pressure monitoring before and between days 6 and 10 of sorafenib therapy . After blood pressure changes were detected among the first cohort within 10 days ,  ambulatory blood pressure monitoring  was done during the first 24 hours of treatment for the second cohort . Results : For the entire patient population , the blood pressure increase [ mean systolic , + 10.8 mm Hg ; 95 % confidence interval ( 95 % CI ) , 8.6 - 13.0 ; range , −5.2 to + 28.7 mm Hg ; mean diastolic , + 8.0 mm Hg ; 95 % CI , 6.3 - 9.7 ; range , −4.4 to + 27.1 mm Hg ] was detected between days 6 and 10 ( P < 0.0001 for both ) and plateaued thereafter . Variability in blood pressure change did not associate with : age , body size , sex , self-reported race , baseline blood pressure , or steady-state sorafenib plasma concentrations . In the second cohort , the blood pressure elevation was detected during the first 24 hours ( mean systolic , + 8.2 mm Hg ; 95 % CI , 5.0 - 11.3 ; mean diastolic , + 6.5 mm Hg ; 95 % CI , 4.7 - 8.3 ; P < 0.0001 for both ) . Conclusions : Ambulatory blood pressure monitoring detects the blood pressure response to VEGF signaling pathway inhibition by sorafenib during the first 24 hours of treatment . The magnitude of blood pressure elevation is highly variable and unpredictable but could be important in optimizing the therapeutic index of VEGF signaling pathway inhibitor therapy . ( Clin Cancer Res 2009;15(19):6250–7 PURPOSE Sorafenib has been found to have significant clinical activity against hepatocellular carcinoma ( HCC ) .  H and -foot skin syndrome ( HFS ) has been described with the usage of sorafenib . It is a dose-limiting toxicity and may lead to compromised efficacy because of dose reduction . METHODS From 14 patients diagnosed with HCC 10 who developed HFS while on treatment with sorafenib were included in this study . Sorafenib was administered orally at a dose of 400 mg twice daily vitamin E usage can be effective in HFS due to sorafenib , therefore vitamin E 300 mg/day was started when HFS occurred . HFS was grade d according to the National Cancer Institute ( NCI ) criteria . RESULTS Grade 2 - 3 HFS was found in 10 of 14 patients . Vitamin E was started to all patients without using topical agents . Mean time to the appearance of HFS was 15 ± 3 days ( range 10 - 22 ) after starting sorafenib . Grade was 3 in 4 patients , 2 in 4 patients and 1 in 2 patients . Vitamin E administration had a marked effect after 10 - 12 days of its initiation . Skin lesions disappeared without any dose modification . CONCLUSION Sorafenib is the gold st and ard for HCC treatment . Dose modification due to HFS decreases the effectiveness of this agent . Adding vitamin E to sorafenib is effective in HFS without dose reduction or treatment interruption . This is the first clinical study to report resolution of HFS with vitamin E due to sorafenib therapy 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 We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ;  451 patients received sorafenib and 452 received placebo .  The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0 
    Output:
    
Sorafenib was associated with a higher risk of adverse effects  than placebo .
The risk for grade 3 - 4 h and -foot skin reactions , rash or desquamation , diarrhea , and hypertension was much higher in the sorafenib treatment group .
These side effects could often be mitigated with appropriate treatment .
CONCLUSIONS Sorafenib was a moderately effective and safe oral drug for use in Child-Pugh A patients with unresectable HCC .
Sorafenib monotherapy is not recommended for treating intermediate-stage HCC .