***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: BACKGROUND & AIMS Codrituzumab , a humanized monoclonal antibody against Glypican-3 ( GPC3 ) that is expressed in hepatocellular carcinoma ( HCC ) , interacts with CD16/FcγRIIIa and triggers antibody-dependent cytotoxicity . Codrituzumab was studied vs. placebo in a r and omized phase II trial in advanced HCC patients who had failed prior systemic therapy . METHODS Patients with advanced HCC who had failed prior systemic therapy , ⩾18years , Eastern cooperative oncology group ( ECOG ) 0 - 1 , Child-Pugh A were r and omized 2:1 to biweekly codrituzumab 1600 mg vs. placebo . Patients were stratified based on GPC3 immunohistochemical expression : 2+/3 + , 1 + , and 0 . Primary endpoint was progression free survival . Secondary endpoints include overall survival ( OS ) , tolerability , pharmacokinetics , and an exploratory endpoint in biomarkers analysis . RESULTS 185 patients were enrolled : 125 received codrituzumab and 60 placebo : Median age 64/63 , 85/75 % male , 46/42 % Asian , ECOG 0 65/63 % , 74/77 % having vascular invasion and /or extra-hepatic metastasis . 84%/70 % had prior sorafenib . Drug exposure was 98.4 % of planned dose , with an identical adverse events profile between the 2 groups . The median progression free survival and overall survival in the codrituzumab vs. placebo groups in months were : 2.6 vs. 1.5 ( hazard ratios 0.97 , p=0.87 ) , and 8.7 vs. 10 ( hazard ratios 0.96 , p=0.82 ) . Projected Ctrough at cycle 3day 1 based exposure , high CD16/FcγRIIIa on peripheral immune cells , and GPC3 expression in the tumor , were all associated with prolonged progression free survival and overall survival . CONCLUSIONS Codrituzumab did not show clinical benefit in this previously treated HCC population . Whether higher codrituzumab drug exposure or the use of CD16 and GPC3 as potential biomarkers would improve outcome remain unanswered questions . LAY SUMMARY Codrituzumab is a manufactured antibody against a liver cancer protein called glypican-3 . In this clinical trial , codrituzumab was not found be effective against liver cancer . It was suggested though that a higher dose of codrituzumab or selecting patients with high level of glypican-3 or its mediator CD16 might improve outcome . CLINICAL TRIAL REGISTRATION This trial is registered at Clinical trials.gov ( NCT01507168 ) Purpose Codrituzumab , a humanized antibody against glypican-3 , is highly expressed in HCC . A phase I study evaluated the combination with sorafenib in HCC . Patients and methods In a 3 + 3 design , codrituzumab was given intravenously in various doses with sorafenib 400 mg twice daily to patients with advanced HCC , age ≥18 , ECOG 0–1 , Child-Pugh A and B7 , adequate organ functions , and no prior systemic therapy , with tumor assessment by RECIST 1.0 and safety by CTCAE 3.0 . PK and pre , during , and post-therapy 124I radiolabeled codrituzumab PET scan imaging were performed . Results 41 patients were enrolled : 2.5 mg/kg weekly ( qw ) ( 12 ) , 5 mg/kg qw ( 12 ) , 10 mg/kg qw ( 3 ) , 1600 mg every 2 weeks ( q2w ) ( 6 ) , and 1600 mg qw ( 7 ) . Two drug limiting toxicities occurred : grade 3 hyponatremia at 5 mg/kg and grade 3 hyponatremia and hyperglycemia at 1600 mg q2w . Adverse events occurred in 80 % of patients , including at least one ≥ grade 3 : ten ( 25 % ) increased AST , three ( 7.5 % ) increased ALT , and ten ( 25 % ) increased lipase . There were no responses and nine ( 25.7 % ) had stable disease . PK Cmax and AUCt  of codrituzumab and sorafenib were comparable to single-agent data . Thirteen out of 14 patients showed 124I radiolabeled codrituzumab uptake in tumor . In all three patients who underwent a post-progression PET , glypican-3 remained expressed . Conclusion Codrituzumab plus sorafenib were tolerated at 1600 mg q2w and 400 mg bid , respectively , with no responses . Codrituzumab exerts selective distribution to HCC cells , and GPC3 does not show any down-regulation post-progression ( NCT00976170 ) Purpose : The carcinoembryonic antigen glypican-3 ( GPC3 ) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma ( HCC ) . In this nonr and omized , open-label , phase I clinical trial , we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC . Experimental Design : Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination ( intradermal injections on days 1 , 15 , and 29 with dose escalation ) . The primary endpoint was the safety of  GPC3 peptide vaccination . The secondary endpoints were immune response , as measured by IFN-γ ELISPOT assay , and the clinical outcomes tumor response , time to tumor progression , and overall survival ( OS ) . Results : GPC3 vaccination was well-tolerated . One patient showed a partial response , and 19 patients showed stable disease 2 months after initiation of treatment . Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response . Levels of the tumor markers α-fetoprotein and /or des-γ-carboxy prothrombin temporarily decreased in nine patients . The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients . Furthermore , GPC3-specific CTL frequency after vaccination correlated with OS . OS was significantly longer in patients with high GPC3-specific CTL frequencies ( N = 15 ) than in those with low frequencies ( N = 18 ; P = 0.033 ) . Conclusions : GPC3-derived peptide vaccination was well-tolerated , and measurable immune responses and antitumor efficacy were noted . This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC  receiving peptide vaccination . Clin Cancer Res ; 18(13 ) ; 3686–96 . © 2012 AACR Glypican-3 ( GPC3 ) is a promising tumor marker for hepatocellular carcinoma ( HCC ) diagnosis with high sensitivity and specificity . The aim of this study was to establish an immunohistochemical detection method for GPC3 using the 7D11 monoclonal antibody ( 7D11 mAb ) and evaluate its application for HCC diagnosis . The feasibility of the 7D11 mAb was evaluated by immunohistochemistry performed on adjacent normal liver and intrahepatic cholangiocarcinoma ( ICC ) sample s , Furthermore , the serum GPC3 levels were evaluated in 40 HCC patients , 7 ICC patients and 50 healthy donors . The results showed that GPC3 was expressed in 85 % of HCC tissues ( 34/40 ) , but was undetectable in ICC tissues and adjacent normal tissues . GPC3 was significantly increased in the serum of HCC patients ( 17/40 , 42.5 % ) but was undetectable in the serum of ICC patients ( 0/7 , 0 % ) and healthy donors(0/50 , 0 % ) . This prospect i ve study evaluated the clinical usefulness of 7D11 mAb for GPC3 detection in HCC patients . In conclusion , the use of 7D11 mAb might be good for GPC3 large-scale applications for clinical diagnosis of HCC GC33 is a humanized mAb against human glypican‐3 ( GPC3 ) . In the first‐in‐human study carried out in the USA , GC33 was well tolerated and showed preliminary antitumor activity in patients with advanced hepatocellular carcinoma . This study aim ed to assess the safety , tolerability , and pharmacokinetic characteristics of GC33 in Japanese patients with advanced hepatocellular carcinoma . The study design was a conventional 3 + 3 dose‐escalation design to determine the maximum tolerated dose of GC33 given i.v . at 5 , 10 , or 20 mg/kg weekly . Immunohistochemistry was carried out on tumor biopsies to evaluate GPC3 expression .  Thirteen patients were enrolled across the three dose levels , and no patients observed any dose‐limiting toxicity up to the highest planned dose of 20 mg/kg . The most common adverse events were decreased lymphocyte count , decreased natural killer cell count , increased C‐reactive protein , and pyrexia . Grade 3 adverse events ( increased blood pressure , decreased lymphocyte count , and decreased platelet count ) were observed in two or more patients . The AUCinf showed a dose‐proportional increase from the 5 mg/kg dose group to the 20 mg/kg dose group . The trough concentrations  of GC33 appeared to reach a steady state after the fourth to the sixth dose . Seven of the 13 patients showed stable disease , the other six showed progressive disease . Furthermore , three patients showed long‐term stable disease of more than 5 months . In conclusion , GC33 given at up to 20 mg/kg weekly was well tolerated in Japanese patients with advanced hepatocellular carcinoma α-Feto  protein ( AFP ) is the widely used tumor marker in the diagnosis of hepatocellular carcinoma ( HCC ) . The aim of this study was to assess the diagnostic and prognostic validity of a novel marker , serum Glypican-3 ( GPC3 ) and to compare AFP in patients with HCC . One hundred and twenty-eight patients ( 75 patients with HCC , 55 patients with cirrhosis , and 28 healthy controls ) were included in this study . Cut-off value of GPC3 was 3.9 pg/ml . AFP was divided into four subgroups , according to cut-off values with 13 , 20 , 100 , and 200 ng/ml . Sensitivity , specificity , and positive and negative predictive values of GPC3 and AFP13 , AFP20 , AFP100 , AFP200 subgroups and also GPC3+AFP13 , GPC3+AFP20 , GPC3+AFP100 , GPC3+AFP200 combinations were compared . Serum GPC3 levels were significantly higher in patients with HCC and cirrhosis compared with control subjects ( P<0.05 ) . The median serum GPC3 levels were 3.9 pg/ml in controls , 5.51 pg/ml in patients with cirrhosis , and 5.13 pg/ml in those with HCC . The median serum AFP levels were 1.37 ng/ml in controls , 2.32 ng/ml in cirrhotics , and 50.65 ng/ml in HCC patients . The sensitivity , specificity , and positive and negative predictive values of GPC3 was 61.33 , 41.82 , 58.97 , and 44.43 % , respectively . The values for AFP were 68.57 , 94.55 , 94.12 , and 70.27 % , respectively . There was no correlation between GPC3 levels and prognostic parameters . GPC3 is not a useful diagnostic and prognostic marker for HCC 
    Output:
    
GPC3 had a nearly similar sensitivity as AFP , while the specificity and AUC of GPC3 was lower than that of AFP .
The combination of GPC3 and AFP yielded a better sensitivity and AUC than GPC3 or AFP .
Serum GPC3 is inferior to AFP in the differential diagnosis between HCC and LC .
However , the combination of GPC3 and AFP exhibited a much better performance