***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: AIM Transcatheter arterial chemoembolization ( TACE ) is an established treatment for unresectable hepatocellular carcinoma ( HCC ) . However , it is unclear which chemotherapeutic agent should be selected for TACE . The aim of this study was to compare the efficacy of cisplatin ( CDDP ) with that of epirubicin ( EPI ) in TACE for patients with unresectable or relapsed HCC . METHODS We performed a historical cohort study involving 131 patients treated with a first TACE , defined as either an initial treatment for previously untreated HCC or a first treatment for relapsed HCC after curative resections or ablations .  Efficacy was estimated as the response rate ( RR ) and it was adjusted for the confounding factors that were defined in this study . RESULTS The RR were 62.5 % ( 20/32 ) for the first TACE with CDDP and 51.5 % ( 51/99 ) for that with EPI . In the adjusted analysis for a history of hepatectomy , percutaneous treatment combined with TACE and tumor factors , the odds ratio was 1.72 ( 95 % confidence interval [ CI ] = 0.70 - 4.48 ) . However , a test for interaction between the number of tumors and the chemotherapeutic agent was statistically significant ( P = 0.016 ) . In multiple HCC , the RR were 66.7 % ( 10/17 ) for CDDP and 39.6 % ( 30/46 ) for EPI . The odds ratio was 4.11 ( 95 % CI = 1.14 - 17.2 ) . CONCLUSION CDDP may be more effective than EPI in TACE for multiple HCC . A r and omized controlled study is needed to clarify the efficacy of CDDP in TACE in patients with multiple HCC The prognosis of patients with hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) is extremely poor . The aim of this study was to eluci date the efficacy of hepatic arterial infusion chemotherapy ( HAIC ) for patients with advanced HCCs Sorafenib targets the Raf/mitogen-activated protein kinase , VEGF , and platelet-derived growth factor pathways and prolongs survival patients in advanced hepatocellular carcinoma ( HCC ) .  Everolimus inhibits the mammalian target of rapamycin , a kinase overactive in HCC . To investigate whether the antitumor effects of these agents are additive , we compared a combined and sequential treatment regimen of everolimus and sorafenib with monotherapy . After hepatic implantation of Morris Hepatoma ( MH ) cells , rats were r and omly allocated to everolimus ( 5 mg/kg , 2 × /week ) , sorafenib ( 7.5 mg/kg/d ) , combined everolimus and sorafenib , sequential sorafenib ( 2 weeks ) then everolimus ( 3 weeks ) , or control groups . MRI quantified tumor volumes . Erk1/2 , 4E-BP1 , and their phosphorylated forms were quantified by immunoblotting . Angiogenesis was assessed in vitro by aortic ring and tube formation assays , and in vivo with Vegf-a mRNA and vascular casts . After 35 days , tumor volumes were reduced by 60 % , 85 % , and 55 % , relative to controls , in everolimus , the combination , and sequential groups , respectively ( P < 0.01 ) . Survival was longest in the combination group ( P < 0.001 ) . Phosphorylation of 4E-BP1 and Erk1/2 decreased after everolimus and sorafenib , respectively . Angiogenesis decreased after all treatments ( P < 0.05 ) , although sorafenib increased Vegf-a mRNA in liver tumors . Vessel sprouting was abundant in control tumors , lower after sorafenib , and absent after the combination . Intussusceptive angiogenic transluminal pillars failed to coalesce after the combination . Combined treatment with everolimus and sorafenib exerts a stronger antitumoral effect on MH tumors than monotherapy . Everolimus  retains antitumoral properties when administered sequentially after sorafenib . This supports the clinical use of everolimus in HCC , both in combination with sorafenib or after sorafenib . Mol Cancer Ther ; 10(6 ) ; 1007–17 . © 2011 AACR In a prospect i ve , multicenter , open‐label study , de novo liver transplant patients were r and omized at day 30±5 to ( i ) everolimus initiation with tacrolimus elimination ( TAC Elimination ) ( ii ) everolimus initiation with reduced‐exposure tacrolimus ( EVR+Reduced TAC ) or ( iii ) st and ard‐exposure tacrolimus ( TAC Control ) . R and omization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection ( tBPAR ) . EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint ( tBPAR , graft loss or death at 12 months posttransplantation ) : 6.7 % versus 9.7 % ( −3.0 % ; 95 % CI −8.7 , 2.6 % ; p<0.001 for noninferiority [ 12 % margin ] ) . tBPAR occurred in 2.9 % of EVR+Reduced TAC patients versus 7.0 % of TAC Controls ( p = 0.035 ) . The change in adjusted estimated GFR from r and omization to month 12 was superior with EVR+Reduced TAC versus TAC Control ( difference 8.50 mL/min/1.73 m2 , 97.5 % CI 3.74 , 13.27 mL/min/1.73 m2 , p<0.001 for superiority ) . Drug discontinuation for adverse events occurred in 25.7 % of EVR+Reduced TAC and 14.1 % of TAC Controls ( relative risk 1.82 , 95 % CI 1.25 , 2.66 ) . Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 ( 95 % CI 1.03 , 3.00 ) . Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function , compared to a st and ard tacrolimus exposure regimen 12 months after liver transplantation Hepatocellular carcinoma ( HCC ) st and s as a major health problem worldwide . The management of advanced HCC , limited for a longtime by the disappointing results of conventional cytotoxic chemotherapies , has recently changed with the publication of the results of the Sorafenib Hepatocellular Carcinoma Assessment R and omized Protocol ( SHARP ) trial , which demonstrated an overall survival benefit over placebo in patients with advanced HCC . This study was further confirmed by the Asian-Pacific trial using sorafenib in Eastern patients . Those trials demonstrated that therapeutic benefits may derive from improving our knowledge of deregulated signaling pathways involved in HCC carcinogenesis . This review summarizes the results of clinical trials in which targeted therapies are currently evaluated aim ing to enlarge the therapeutic armamentarium for HCC in a near future We present the 12-month results of a prospect i ve trial of conversion from calcineurin inhibitors ( CNI ) to everolimus ( EVL ) in maintenance liver transplant ( LT ) recipients . Forty ( M : F = 28:12 ; 54.9 + /- 11 years ) patients were enrolled at a mean interval of 45.5 + /- 31.2 months from transplantation . Conversion was with EVL at a dosage of 0.75 mg b.i.d . , withdrawal of antimetabolites , and a 50%-per-week reduction of CNI to a complete stop within 4 weeks . The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI , death , and graft loss . Indication to conversion was deteriorating renal function in 36 ( 90 % ) . At 12 months , patient- and graft survival were 100 % and the success rate was 75 % ( 30/40 ) . Ten patients ( 25 % ) were failures : four ( 10 % ) for acute rejection ; three hepatitis C virus-RNA positive patients ( 7.5 % ) for hypertransaminasemia ; one ( 2.5 % ) for acute cholangitis ; and two ( 5 % ) due to persistent pruritus and oral ulcers . In patients on EVL monotherapy , at 12 months the mean change of calculated creatinine clearance ( cCrCl ) was 4.03 + /- 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl ( P < 0.0001 ) . Conversion from CNI to EVL is feasible in 75 % of the cases and associated with improvement in renal function for patients with higher baseline cCrCl Data on the conversion of patients to everolimus after liver transplantation are sparse . A multicenter , retrospective study followed 240 maintenance liver transplant patients to analyze the current indications for everolimus conversion , the employed regimens and exposure levels , and the impact on efficacy and safety . The mean time from transplantation to the introduction of everolimus was 4.9 ± 5.2 years . The mean everolimus trough level was 7.3 ± 4.1 ng/mL at month 1 and 8.1 ± 4.7 ng/mL at month 12 . At 12 months , 61.6 % of the patients were no longer receiving calcineurin inhibitor ( CNI ) therapy . The mean estimated glomerular filtration rate ( eGFR ) according to the Cockcroft-Gault formula was 64.2 ± 30.0 mL/minute on day 0 and 68.4 ± 32.5 mL/minute at month 12 ( P = 0.007 ) . Among patients with baseline serum creatinine levels ≥ 130 μmol/L , the eGFR values were 44.3 ± 15.7 mL/minute on day 0 and 53.7 ± 26.0 mL/minute at month 12 ( P = 0.003 ) . Four patients ( 1.6 % ) developed mild or moderate biopsy-proven acute rejection . Adverse events led to everolimus discontinuation in 12.9 % of the patients . After the initiation of everolimus  , the mean white blood cell count decreased significantly , and the total cholesterol and triglyceride levels increased significantly . In this retrospective analysis of the largest cohort of maintenance liver transplant patients analyzed after their conversion to everolimus , more than 60 % of the patients were kept free of CNIs with a very low risk of acute rejection and with an acceptable safety profile . R and omized trials in which maintenance liver transplant patients are switched to everolimus in response to clinical indications or preemptively are warranted BACKGROUND Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin ( mTOR ) intracellular signaling pathway . In early studies , the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity . METHODS In this phase 3 , r and omized trial , we compared everolimus and exemestane versus exemestane and placebo ( r and omly assigned in a 2:1 ratio ) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease ( or both ) . The primary end point was progression-free survival . Secondary end points included survival , response rate , and safety . A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed . RESULTS Baseline characteristics were well balanced between the two study groups . The median age was 62 years , 56 % had visceral involvement , and 84 % had hormone-sensitive disease . Previous therapy included letrozole or anastrozole ( 100 % ) , tamoxifen ( 48 % ) , fulvestrant ( 16 % ) , and chemotherapy ( 68 % ) . The most common grade 3 or 4 adverse events were stomatitis ( 8 % in the everolimus-plus-exemestane group vs. 1 % in the placebo-plus-exemestane group ) , anemia ( 6 % vs. < 1 % ) , dyspnea ( 4 % vs. 1 % ) , hyperglycemia ( 4 % vs. < 1 % ) , fatigue ( 4 % vs. 1 % ) , and pneumonitis ( 3 % vs. 0 % ) . At the interim analysis , median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane , according to assessment s by local investigators ( hazard ratio for progression or death , 0.43 ; 95 % confidence interval [ CI ] , 0.35 to 0.54 ; P<0.001 ) . Median progression-free survival was 10.6 months and 4.1 months , 
    Output:
    
Manypre clinical studies demonstrated that everolimus had antitumor effects such as antiproliferation and antiangiogenesis .
However , some differences in the effects were observed among in vivo animal studies for HCC treatment .
Meanwhile , clinical studies demonstrated that the response rate of single-agent everolimus was low , though survival benefits could be expected .
Everolimus at the dose of 10 mg/day significantly increased the risk of the adverse events .