Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we rep...Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.展开更多
AIM:To determine the clinical value of a splenorenal shunt plus pericardial devascularization(PCVD)in portal hypertension(PHT)patients with variceal bleeding.METHODS:From January 2008 to November 2012,290 patients wit...AIM:To determine the clinical value of a splenorenal shunt plus pericardial devascularization(PCVD)in portal hypertension(PHT)patients with variceal bleeding.METHODS:From January 2008 to November 2012,290 patients with cirrhotic portal hypertension were treated surgically in our department for the prevention of gastroesophageal variceal bleeding:207 patients received a routine PCVD procedure(PCVD group),and83 patients received a PCVD plus a splenorenal shunt procedure(combined group).Changes in hemodynamic parameters,rebleeding,encephalopathy,portal vein thrombosis,and mortality were analyzed.RESULTS:The free portal pressure decreased to 21.43±4.35 mmHg in the combined group compared with24.61±5.42 mmHg in the PCVD group(P<0.05).The changes in hemodynamic parameters were more significant in the combined group(P<0.05).The long-term rebleeding rate was 7.22%in the combined group,which was lower than that in the PCVD group(14.93%),(P<0.05).CONCLUSION:Devascularization plus splenorenal shunt is an effective and safe strategy to control esophagogastric variceal bleeding in PHT.It should be recommended as a first-line treatment for preventing bleeding in PHT patients when surgical interventions are considered.展开更多
Aim:According to the current guidelines,transarterial chemoembolization(TACE)remains the first-line therapies for hepatocellular carcinoma(HCC)patients at Barcelona Clinic Liver Cancer(BCLC)B-stage and sorafenib is a ...Aim:According to the current guidelines,transarterial chemoembolization(TACE)remains the first-line therapies for hepatocellular carcinoma(HCC)patients at Barcelona Clinic Liver Cancer(BCLC)B-stage and sorafenib is a small molecule target drug for BCLC C-stage.In clinical practice,clinicians have attempted to use stereotactic body radiation therapy(SBRT)plus TACE for treating intermediate-to advanced-stage HCC.However,the therapeutic effects are still inconsistent.This meta-analysis was conducted to elucidate the validity and safety of the combination therapy of SBRT plus TACE in the patients with intermediate-to advanced-stage HCC.Methods:PubMed,MEDLINE,Web of Science,China Biology Medicine,Chinese Knowledge resources integrated and Chinese Scientific Journal Full-Text Database was searched from their inception date to November 2018.The survival rates(half-year,one-year and two-year)were analyzed and compared between the observation groups and the control groups.The negative conversion rate of AFP and the total effective rate were also assessed.Risk ratios(RR)and 95%CI were calculated to express therapeutic effects. ;Results:A total of 1,210 patients from 13 eligible studies were included.The cooperation of TACE and SBRT notably ameliorated the whole survival rates of half-year,one-year,two-year,the negative conversion rate of AFP,and the total effective rate,compared with TACE or SBRT monotherapy[RR(the total effective rate),1.412,95%CI:1.309-1.523,P<0.001],[RR(half-year survival rate),1.196,95%CI:1.121-1.276,P<0.001],[RR(one-year survival rate),1.327,95%CI:1.236-1.424,P<0.001],[RR(two-year survival rate),1.479,95%CI:1.284-1.703,P<0.001]and[RR(negative conversion rate of AFP),1.756,95%CI:1.502-2.059,P<0.001].Sensitivity analysis supported the above results.Conclusion:Combination therapy of SBRT and TACE provides survival benefits in intermediate-to advanced-stage HCC patients compared to monotherapy of SBRT or TACE.展开更多
Aim:This meta-analysis was designed to compare the effectiveness of the combination of transarterial chemoembolization(TACE)and radiofrequency ablation(RFA)vs.that of TACE alone in hepatocellular carcinoma(HCC)tumors ...Aim:This meta-analysis was designed to compare the effectiveness of the combination of transarterial chemoembolization(TACE)and radiofrequency ablation(RFA)vs.that of TACE alone in hepatocellular carcinoma(HCC)tumors larger than 5 cm.Methods:PUBMED,CNKI,and CBM were searched for all related randomized controlled trials(RCTs)up until October 22,2018.Eleven studies were identified that compared TACE with RFAvs.TACE alone for HCC treatment.Tumor response rate,the proportion of patients with either complete or partial shrinkage of tumors,and survival rate were the major evaluation indices.Results:Meta-analysis data revealed that TACE with RFA showed significantly better tumor response rate(risk ratio(RR)=1.452,95%confidence interval(CI):1.308-1.610,P<0.001)and 1-year overall survival rate(RR=1.412,95%CI:1.249-1.596,P<0.001)than that of TACE alone treatment.Conclusion:The data of our study indicates that TACE combined with RFA in the treatment of HCC larger than 5 cm is an effective comprehensive interventional therapy.展开更多
To the Editor:Lung cancer leads to the largest number of cancer-associated deaths in the world.As the main means of the spreading of lung cancer,lymph node metastasis is related to the strategy for its treatment and t...To the Editor:Lung cancer leads to the largest number of cancer-associated deaths in the world.As the main means of the spreading of lung cancer,lymph node metastasis is related to the strategy for its treatment and the prognosis of the patients.[1]According to guidelines of the National Comprehensive Cancer Network,once mediastinal lymph nodes have been involved,patients are considered to have reached an advanced stage of lung cancer,and the treatment strategy should be different.[2]Computed tomography(CT)is a common method for the preoperative prediction of lymph node metastasis among lung cancer patients.However,not all abnormal lymph nodes can be recognized preoperatively with CT.Thus,more accurate prediction of lymph node metastasis is important for lung cancer treatment.展开更多
Background and aims:Splenomegaly often occurs in cirrhotic patients with portal hypertension(PHT),and therefore,the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question i...Background and aims:Splenomegaly often occurs in cirrhotic patients with portal hypertension(PHT),and therefore,the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question in these patients.Here,we developed a novel approach to assess true splenic volume more precisely.Methods:High-quality thin-slice computed tomography data of 112 cirrhotic patients with PHT were obtained and reviewed.Both the conventional measurement and a novel formula obtained from 3-dimensional reconstruction software were used to estimate splenic volume,and the accuracy was compared and verified.Results:In PHT patients,the splenic volume calculated using the conventional method was significantly less than that calculated using the 3-dimensional software.We found that the splenic volume was significantly positively correlated with splenic indices of length(L),thickness(T),and width(W)and also the diameter of the splenic vein.Using these indices,we propose 2 novel formulas using the software to estimate the splenic volume more accurately:SV=69.686 L+53.077 W+103.525 T+314.510 diameter of splenic vein 2266.209(p<0.01,R^(2)=0.805).And a more practical simplified formula:SV'=0.504× L× W×T+319.762 diameter of splenic vein 81.66(p<0.01,R^(2)=0.784).Conclusion:Although the conventional formula has been widely used for years,it is not suitable for an enlarged spleen.We developed 2 novel formulas for estimating splenic volume from clinical data that were more appropriate for cirrhotic patients with PHT.展开更多
WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell l...WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.展开更多
To provide a new method to estimate the effectiveness of thoracolumbar vertebral finite element model. Methods: A mechanical model of human thoracolumbar vertebrae motion segment was made using three-dimensional finit...To provide a new method to estimate the effectiveness of thoracolumbar vertebral finite element model. Methods: A mechanical model of human thoracolumbar vertebrae motion segment was made using three-dimensional finite element method and the stress distribution of vertically compressed thoracolumbar vertebrae was analyzed, meanwhile, 20 patients with burst fracture of thoracolumbar vertebrae were tested by CT to calculated average CT value at ascertained different points of thoracolumbar vertebrae. The calculated results and effective stress at the same position were analyzed with straight line correlation. Results: The stress level of different position of thoracolumbar vertebrae under vertical compressive force was positively correlated with the correlative CT value, and the regressive style, Y= 214.028 + 45.268 X, r= 0.7386 , P< 0.05 (n=8) showed a statistical significance.Conclusions: To study mechanism of thoracolumbar vertebrae injuries under different forces has clinical significance.展开更多
基金funded by Shanghai Henlius Biotech, Inc., Science and Technology Commission of Shanghai Municipality (No. 14431908500)China National Major Project for New Drug Innovation (No. 2012ZX09303012)。
文摘Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.
文摘AIM:To determine the clinical value of a splenorenal shunt plus pericardial devascularization(PCVD)in portal hypertension(PHT)patients with variceal bleeding.METHODS:From January 2008 to November 2012,290 patients with cirrhotic portal hypertension were treated surgically in our department for the prevention of gastroesophageal variceal bleeding:207 patients received a routine PCVD procedure(PCVD group),and83 patients received a PCVD plus a splenorenal shunt procedure(combined group).Changes in hemodynamic parameters,rebleeding,encephalopathy,portal vein thrombosis,and mortality were analyzed.RESULTS:The free portal pressure decreased to 21.43±4.35 mmHg in the combined group compared with24.61±5.42 mmHg in the PCVD group(P<0.05).The changes in hemodynamic parameters were more significant in the combined group(P<0.05).The long-term rebleeding rate was 7.22%in the combined group,which was lower than that in the PCVD group(14.93%),(P<0.05).CONCLUSION:Devascularization plus splenorenal shunt is an effective and safe strategy to control esophagogastric variceal bleeding in PHT.It should be recommended as a first-line treatment for preventing bleeding in PHT patients when surgical interventions are considered.
基金This study was funded by the National Natural Science Foundations of China(81773488,81172287).
文摘Aim:According to the current guidelines,transarterial chemoembolization(TACE)remains the first-line therapies for hepatocellular carcinoma(HCC)patients at Barcelona Clinic Liver Cancer(BCLC)B-stage and sorafenib is a small molecule target drug for BCLC C-stage.In clinical practice,clinicians have attempted to use stereotactic body radiation therapy(SBRT)plus TACE for treating intermediate-to advanced-stage HCC.However,the therapeutic effects are still inconsistent.This meta-analysis was conducted to elucidate the validity and safety of the combination therapy of SBRT plus TACE in the patients with intermediate-to advanced-stage HCC.Methods:PubMed,MEDLINE,Web of Science,China Biology Medicine,Chinese Knowledge resources integrated and Chinese Scientific Journal Full-Text Database was searched from their inception date to November 2018.The survival rates(half-year,one-year and two-year)were analyzed and compared between the observation groups and the control groups.The negative conversion rate of AFP and the total effective rate were also assessed.Risk ratios(RR)and 95%CI were calculated to express therapeutic effects. ;Results:A total of 1,210 patients from 13 eligible studies were included.The cooperation of TACE and SBRT notably ameliorated the whole survival rates of half-year,one-year,two-year,the negative conversion rate of AFP,and the total effective rate,compared with TACE or SBRT monotherapy[RR(the total effective rate),1.412,95%CI:1.309-1.523,P<0.001],[RR(half-year survival rate),1.196,95%CI:1.121-1.276,P<0.001],[RR(one-year survival rate),1.327,95%CI:1.236-1.424,P<0.001],[RR(two-year survival rate),1.479,95%CI:1.284-1.703,P<0.001]and[RR(negative conversion rate of AFP),1.756,95%CI:1.502-2.059,P<0.001].Sensitivity analysis supported the above results.Conclusion:Combination therapy of SBRT and TACE provides survival benefits in intermediate-to advanced-stage HCC patients compared to monotherapy of SBRT or TACE.
基金This study was funded by National Natural Science Foundations of China(81773488 and 8177110260).
文摘Aim:This meta-analysis was designed to compare the effectiveness of the combination of transarterial chemoembolization(TACE)and radiofrequency ablation(RFA)vs.that of TACE alone in hepatocellular carcinoma(HCC)tumors larger than 5 cm.Methods:PUBMED,CNKI,and CBM were searched for all related randomized controlled trials(RCTs)up until October 22,2018.Eleven studies were identified that compared TACE with RFAvs.TACE alone for HCC treatment.Tumor response rate,the proportion of patients with either complete or partial shrinkage of tumors,and survival rate were the major evaluation indices.Results:Meta-analysis data revealed that TACE with RFA showed significantly better tumor response rate(risk ratio(RR)=1.452,95%confidence interval(CI):1.308-1.610,P<0.001)and 1-year overall survival rate(RR=1.412,95%CI:1.249-1.596,P<0.001)than that of TACE alone treatment.Conclusion:The data of our study indicates that TACE combined with RFA in the treatment of HCC larger than 5 cm is an effective comprehensive interventional therapy.
基金Natural Science Foundation of Shandong Province(No.ZR2020HM234)
文摘To the Editor:Lung cancer leads to the largest number of cancer-associated deaths in the world.As the main means of the spreading of lung cancer,lymph node metastasis is related to the strategy for its treatment and the prognosis of the patients.[1]According to guidelines of the National Comprehensive Cancer Network,once mediastinal lymph nodes have been involved,patients are considered to have reached an advanced stage of lung cancer,and the treatment strategy should be different.[2]Computed tomography(CT)is a common method for the preoperative prediction of lymph node metastasis among lung cancer patients.However,not all abnormal lymph nodes can be recognized preoperatively with CT.Thus,more accurate prediction of lymph node metastasis is important for lung cancer treatment.
基金by the Ethical Committee of Tangdu Hos-pital(approval number:K202001-07).
文摘Background and aims:Splenomegaly often occurs in cirrhotic patients with portal hypertension(PHT),and therefore,the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question in these patients.Here,we developed a novel approach to assess true splenic volume more precisely.Methods:High-quality thin-slice computed tomography data of 112 cirrhotic patients with PHT were obtained and reviewed.Both the conventional measurement and a novel formula obtained from 3-dimensional reconstruction software were used to estimate splenic volume,and the accuracy was compared and verified.Results:In PHT patients,the splenic volume calculated using the conventional method was significantly less than that calculated using the 3-dimensional software.We found that the splenic volume was significantly positively correlated with splenic indices of length(L),thickness(T),and width(W)and also the diameter of the splenic vein.Using these indices,we propose 2 novel formulas using the software to estimate the splenic volume more accurately:SV=69.686 L+53.077 W+103.525 T+314.510 diameter of splenic vein 2266.209(p<0.01,R^(2)=0.805).And a more practical simplified formula:SV'=0.504× L× W×T+319.762 diameter of splenic vein 81.66(p<0.01,R^(2)=0.784).Conclusion:Although the conventional formula has been widely used for years,it is not suitable for an enlarged spleen.We developed 2 novel formulas for estimating splenic volume from clinical data that were more appropriate for cirrhotic patients with PHT.
基金This study(NCT03389815)was funded by Qilu Pharmaceutical Co.,Ltd.and also supported in part by China National Major Project for New Drug Innovation(2017ZX09304015)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-001).
文摘WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.
文摘To provide a new method to estimate the effectiveness of thoracolumbar vertebral finite element model. Methods: A mechanical model of human thoracolumbar vertebrae motion segment was made using three-dimensional finite element method and the stress distribution of vertically compressed thoracolumbar vertebrae was analyzed, meanwhile, 20 patients with burst fracture of thoracolumbar vertebrae were tested by CT to calculated average CT value at ascertained different points of thoracolumbar vertebrae. The calculated results and effective stress at the same position were analyzed with straight line correlation. Results: The stress level of different position of thoracolumbar vertebrae under vertical compressive force was positively correlated with the correlative CT value, and the regressive style, Y= 214.028 + 45.268 X, r= 0.7386 , P< 0.05 (n=8) showed a statistical significance.Conclusions: To study mechanism of thoracolumbar vertebrae injuries under different forces has clinical significance.
