***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: Summary Background The combination of bevacizumab ( B ) and erlotinib ( E ) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients . We aim ed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment . Methods Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited . All patients received bevacizumab(B ) at 10 mg/kg every 2 weeks with erlotinib(E ) at 150 mg daily for a maximum of 6 cycles . Response assessment s using both RECIST and modified RECIST criteria were performed after every 6 weeks . The primary endpoint was clinical benefit ( CB ) rate and a Simon two-stage design was employed . Results The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited . The median age was 47 years ( range , 28–61 ) and all patients were in ECOG performance status 1 . Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis . Among these 10 patients , none of the enrolled patients achieved response or stable disease . The median time-to-progression was 1.81 months ( 95 % confidence interval [ C.I. ] , 1.08–1.74 months ) and overall survival was 4.37 months ( 95 % C.I. , 1.08–11.66 months ) . Rash ( 70 % ) , diarrhea ( 50 % ) and malaise ( 40 % ) were the most commonly encountered toxicities . Conclusion The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population . Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population 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 PURPOSE Hepatocellular carcinoma ( HCC ) is a vascular tumor with poor prognosis . Given the reported activity of gemcitabine and oxaliplatin ( GEMOX ) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab ( B ) , a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients . PATIENTS AND METHODS Eligible patients had pathologically proven measurable unresectable or metastatic HCC . For cycle 1 ( 14 days ) , bevacizumab 10 mg/kg was administered alone intravenously on day 1 . For cycle 2 and beyond ( 28 days/cycle ) , bevacizumab 10 mg/kg was administered on days 1 and 15 , gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16 . RESULTS Thirty-three patients were enrolled and 30 patients were assessable for  efficacy  . The objective response rate was 20 % , and 27 % of patients had stable disease . Median overall survival was 9.6 months ( 95 % CI , 8.0 months to not available ) and median progression-free survival ( PFS ) was 5.3 months ( 95 % CI , 3.7 to 8.7 months ) ; the PFS rate at 3 and 6 months was 70 % ( 95 % CI , 54 % to 85 % ) and 48 % ( 95 % CI , 31 % to 65 % ) , respectively . The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia , transient elevation of aminotransferases , hypertension , and fatigue . CONCLUSION GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC . The high 6-month PFS rate is encouraging , and this regimen is worthy of further investigation BACKGROUND The growing availability of active agents makes the development of novel therapies increasingly complex and the choice of end points critical . We assessed the frequency of use of efficacy end points in advanced breast cancer . METHODS We search ed PubMed for r and omized trials published between 2000 and 2007 in 10 leading medical journals . We abstract ed data on  progression-free survival ( PFS ) , time to tumor progression ( TTP ) , response rate ( RR ) and overall survival .  RESULTS A total of 58 studies enrolled 23,371 assessable patients in 122 treatment arms . The primary end points most frequently used were RR and TTP ( n=21 each ) , followed by PFS ( n=14 ) . In five of the trials using TTP as the primary end point , no definition of TTP was reported ; in 13 of the other 16 cases , death was counted as an event , making TTP indistinguishable from PFS . Trials having PFS , TTP or time to treatment failure as the primary end point ( n=36 ) had a higher mean number of patients than those using RR ( P=0.061 ) . CONCLUSION Investigators seem to be frequently using PFS and TTP interchangeably in advanced breast cancer . Such use of terms may lead to confusion when results of different trials are compared , and uniform use of definitions seems in order Epidermal growth factor receptor ( EGFR ) and vascular endothelial growth factor ( VEGF ) are rational targets for therapy in hepatocellular cancer ( HCC ) Background : Molecularly targeted agents with anti-angiogenic activity , including bevacizumab , have demonstrated clinical activity in patients with advanced/metastatic hepatocellular carcinoma ( HCC ) . This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population . Methods : Histologically proven/ clinical ly diagnosed advanced HCC patients received bevacizumab 7.5 mg kg–1 on day 1 and capecitabine 800 mg m–2 twice daily on days 1–14 every 3 weeks as first-line therapy . Results : A total of 45 patients were enrolled ; 44 ( 96 % ) had extrahepatic metastasis and /or major vessel invasion and 30 ( 67 % ) had hepatitis B.  No grade 3/4 haematological toxicity occurred . Treatment-related grade 3/4 non-haematological toxicities included diarrhoea ( n=2 , 4 % ) , nausea/vomiting ( n=1 , 2 % ) , gastrointestinal bleeding ( n=4 , 9 % ) and h and –foot syndrome ( n=4 , 9 % ) . The overall response rate ( RECIST ) was 9 % and the disease control rate was 52 % . Overall , median progression-free survival ( PFS ) and overall survival ( OS ) were 2.7 and 5.9 months , respectively . Median PFS and OS were 3.6 and 8.2 months , respectively , for Cancer of the Liver Italian Programme ( CLIP ) score ⩽3 patients , and 1.4 and 3.3 months , respectively , for CLIP score 4 patients . Conclusion : The bevacizumab – capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC Growth factor overexpression , including epidermal growth factor receptor ( EGFR ) expression , is common in hepatocellular cancers . Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR . The primary objective of this study was to determine the proportion of hepatocellular carcinoma ( HCC ) patients treated with erlotinib who were alive and progression‐free ( PFS ) at 16 weeks of continuous treatment BACKGROUND Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma ( HCC ) , but the response rate is low ( < 20 % ) and there is no convincing evidence for improved survival .  Cisplatin , interferon , doxorubicin , and fluorouracil ( PIAF ) used in combination , by contrast , has shown promise in a phase II study . We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial . METHODS Patients with histologically confirmed unresectable HCC were r and omly assigned to receive either doxorubicin or PIAF every 3 weeks , for up to six cycles . The primary endpoint was overall survival , and secondary endpoints were response rate and toxicity . Survival differences were calculated using the Kaplan-Meier method . Treatment groups were compared for differences in the incidence of adverse events using chi-square tests . All statistical tests were two-sided . RESULTS The median survival of the doxorubicin and PIAF groups was 6.83 months ( 95 % confidence [ CI ] = 4.80 to 9.56 ) and 8.67 months ( 95 % CI = 6.36 to 12.00 ) , respectively ( P = 0.83 ) . The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 ( 95 % CI = 0.71 to 1.32 ) . Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response . The overall response rates in the doxorubicin and PIAF groups were 10.5 % ( 95 % CI = 3.9 % to 16.9 % ) and 20.9 % ( 95 % CI = 12.5 % to 29.2 % ) , respectively . Neutropenia , thrombocytopenia , and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin . CONCLUSION Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin , the differences were not statistically significant . PIAF was also associated with increased treatment-related toxicity . The prognosis of patients with unresectable HCC remains poor PURPOSE Epidermal growth factor receptor/human epidermal growth factor receptor 1 ( EGFR/HER1 ) and lig and expression is frequently seen in hepatocellular cancers ( HCCs ) . Erlotinib ( Tarceva , OSI-774 ; OSI Pharmaceuticals , Melville , NY ) is a receptor tyrosine kinase inhibitor with specificity for the EGFR/HER1 . METHODS The primary objective of this study was to determine the proportion of patients with advanced HCC who were progression-free at 6 months . Patients with either unresectable or metastatic disease were studied . Only one prior systemic or locoregional therapy was allowed . Erlotinib was given continuously at a dose of 150 mg per day orally . RESULTS Thirty-eight patients with HCC were enrolled . Median age of the patients was 69 years ( range , 27 to 83 years ) . A majority of patients ( 63 % ) had an Eastern Cooperative Oncology Group performance status of 1 . Forty-seven percent of patients had received prior chemotherapy for advanced HCC . EGFR/HER1 expression was detected in 88 % of the patients . Median number of cycles per patient was two ( range , 1 to 26 ) . Twelve ( 32 % ; CI 95 % , 18 to 49 ) of the 38 patients with HCC were progression-free at 6 months . Three patients had partial radiologic responses of duration of 2 , 10 , and 11 months , respectively . Disease control was seen in 59 % of the patients . Median overall survival time was 13 months . Ten patients ( 26 % ) had toxicity-related dose reductions of erlotinib . Grade 3/4 skin toxicity or diarrhea was encountered in five and three patients , respectively . CONCLUS 
    Output:
    
Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC .
The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib , the only currently approved treatment for unresectable HCC .