The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evalua...The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.展开更多
Background Neovascular glaucoma （NVG） is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab （IVB） injection in conjunct...Background Neovascular glaucoma （NVG） is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab （IVB） injection in conjunction with Ahmed glaucoma valve implantation （AGVI） in the management of NVG. Methods This was a retrospective study of patients with NVG in whom AGVI was performed between October 2008 and May 2012. The sample was divided into two groups according to the pretreatment： with adjunctive IVB injection （the IVB group, n=25 eyes） and without adjunctive IVB injection （the control group, n=28 eyes）. The surgical success rate, number of antiglaucoma medications used, best-corrected visual acuity （BCVA）, postoperative complications, regression, and recurrence of iris neovascularization （NVI） were analyzed between the groups. Results The surgical outcomes of the two groups were compared. The complete success rates in the IVB and control groups were 84.0% and 64.3% at 12 months and 80.0% and 53.6% at 18 months, respectively. There was a significant difference between the two groups （P=0.041）. Mean postoperative intraocular pressures, mean number of postoperative antiglaucoma medications, and BCVA were not significant between the two groups. The NVI in 22 （88.0%） eyes had completely regressed within 2-8 days after IVB. However, NVI recurred in 10 eyes （40.0%） 2-9 months later after IVB. The IVB group had only 1 case （4.0%） of hyphema out of 25 eyes, while there were 8 （28.6%） cases of hyphema out of 28 eyes in the control group （P=0.026）.Conclusions This study showed that preoperative IVB injection reduced NVI remarkably, decreased hyphema, and led to higher surgical success rates. Pre-operative IVB injection may be an effective adjunct to AGVI in the management of NVG.展开更多
Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their ...Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors （＂small molecule inhibitors＂） and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin （mTOR） upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, roTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.展开更多
文摘The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.
基金ZHOU Min-wen and WANG Wei contributed equallyto this study. This research was supported by grants from the National Natural Science Foundation of China （No. 81170849）, and the Fundamental Research Funds of State Key Laboratory of Ophthalmology （No. 2011 C02）.
文摘Background Neovascular glaucoma （NVG） is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab （IVB） injection in conjunction with Ahmed glaucoma valve implantation （AGVI） in the management of NVG. Methods This was a retrospective study of patients with NVG in whom AGVI was performed between October 2008 and May 2012. The sample was divided into two groups according to the pretreatment： with adjunctive IVB injection （the IVB group, n=25 eyes） and without adjunctive IVB injection （the control group, n=28 eyes）. The surgical success rate, number of antiglaucoma medications used, best-corrected visual acuity （BCVA）, postoperative complications, regression, and recurrence of iris neovascularization （NVI） were analyzed between the groups. Results The surgical outcomes of the two groups were compared. The complete success rates in the IVB and control groups were 84.0% and 64.3% at 12 months and 80.0% and 53.6% at 18 months, respectively. There was a significant difference between the two groups （P=0.041）. Mean postoperative intraocular pressures, mean number of postoperative antiglaucoma medications, and BCVA were not significant between the two groups. The NVI in 22 （88.0%） eyes had completely regressed within 2-8 days after IVB. However, NVI recurred in 10 eyes （40.0%） 2-9 months later after IVB. The IVB group had only 1 case （4.0%） of hyphema out of 25 eyes, while there were 8 （28.6%） cases of hyphema out of 28 eyes in the control group （P=0.026）.Conclusions This study showed that preoperative IVB injection reduced NVI remarkably, decreased hyphema, and led to higher surgical success rates. Pre-operative IVB injection may be an effective adjunct to AGVI in the management of NVG.
文摘Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer （HCC）. Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors （＂small molecule inhibitors＂） and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin （mTOR） upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, roTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.
