Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently ava...Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.展开更多
Objective The aim of this study was to assess the value of palliative local treatment of incurable metastatic lesions in colorectal cancer(CRC) patients receiving chemotherapy plus bevacizumab.Methods Data of 105 pati...Objective The aim of this study was to assess the value of palliative local treatment of incurable metastatic lesions in colorectal cancer(CRC) patients receiving chemotherapy plus bevacizumab.Methods Data of 105 patients with histologically confirmed synchronous or metachronous metastatic CRC who received bevacizumab treatment from January 1, 2011 to January 31, 2017 were retrospectively reviewed. Sixteen(15%) patients who were treated with bevacizumab for less than 4 cycles were excluded, and finally, 89(85%) patients were enrolled. Among them, 33(37%) patients who received palliative local treatment were categorized into the palliative local treatment group, and the remaining 56(63%) patients were categorized into the chemotherapy plus bevacizumab group. The primary endpoint was overall survival(OS), which was calculated using Kaplan-Meier survival analyses. Factors possibly influencing survival were evaluated by univariate and multivariate analyses. Adverse events(AEs) were graded according to Common Terminology Criteria for Adverse Events, version 4.0. Grades 1–2 and 3–4 AEs of the two groups were compared and analyzed using the Fisher's exact test and χ~2 analysis.Results The median follow-up period was 20.4 months, ranging from 1 to 60 months. The median OS in the palliative local treatment group was 36.3 months(95% CI, 33.5–39.2), and that in the chemotherapy plus bevacizumab group was 20.5 months(95% CI, 17.6–23.4). Both the univariate(HR 0.13, 95% CI, 0.05–0.30, P < 0.001) and multivariate(HR 0.16, 95% CI, 0.07–0.39, P < 0.001) analyses showed that the addition of palliative local treatment could prolong survival compared with chemotherapy plus bevacizumab alone. There were no significant differences in the rates of common chemotherapy-or bevacizumab-related AEs between the two groups.Conclusion These findings suggest palliative local treatment is an effective and safe method for treating patients with incurable metastatic CRC receiving chemotherapy plus bevacizumab.展开更多
AIM: To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor(VEGF) treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor...AIM: To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor(VEGF) treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor(VEGFR) expressions were evaluated following repeated bevacizumab treatments in hypoxic human umbilical vein endothelial cells(HUVECs) in vitro.METHODS: HUVECs were incubated under hypoxic conditions in two media of different bevacizumab concentrations(1.0 or 2.5 mg/m L) for 17 h, and then in a new medium without bevacizumab for 7h. This procedure was repeated twice more. A culture with an identical volume of excipients served as the control. Cytotoxicity and cell proliferation were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and Ki-67 assays, respectively. Levels of VEGF and VEGFR were assessed using enzyme-linked immunosorbent assay and Western blot respectively.RESULTS: Cytotoxic effects were not reported for either bevacizumab concentration. Cell proliferation was not reduced after anti-VEGF treatments. VEGF level after single treatment was significantly higher than that of the control and after repeated treatments. Phosphorylated VEGFR-2 expression increased significantly after singleand repeated bevacizumab treatments compared with the control. The 1.0 mg/m L bevacizumab induced significantly higher expressions of VEGFR-2 than the 2.5 mg/m L in single and repeated treatment groups.CONCLUSION: Bevacizumab treatment of HUVECs elevated VEGFR expression in both single and repeated treatments, indicating a mechanism for the reduced efficacy of anti-VEGF therapy in ocular neovascular disorders.展开更多
Background:To compare the structural outcome of intravitreal bevacizumab(IVB)and laser treatment for type 1 retinopathy of prematurity(ROP).Methods:This is a retrospective comparative study.From December 2002 to April...Background:To compare the structural outcome of intravitreal bevacizumab(IVB)and laser treatment for type 1 retinopathy of prematurity(ROP).Methods:This is a retrospective comparative study.From December 2002 to April 2009,patients with type 1ROP according to criteria of Early Treatment of Retinopathy of Prematurity(ETROP)study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern.From May 2009 to January 2015,we performed IVB for patients with type 1 ROP.The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group.The demographical data,postmenstrual age(PMA)for treatment,and fundus findings were recorded by chart review.The difference between laser and bevacizumab groups was compared by Student t-test and Fisher exact test.Results:We collected 43 patients(86 eyes)with type 1 ROP,including 30 male and 13 female infants.Their mean gestation age and birth body weight(BBW)were 27.5 weeks and 1,034 gm.Zone I and zone II disease were found in 8 and 35 patients.The mean PMA for treatment was 37.3 weeks.The mean follow-up period was54.4 months.Laser treatment was administered in 26 patients,and bevacizumab injection for 17 infants.Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization.Complete regression of ROP was found in 15 infants of bevacizumab group following the first IVB.Four eyes in two patients(2/17,11.7%)had recurrence of ROP and received additional injections and adjuvant laser treatment.There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management.Conclusions:Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes.Single session of laser ablation in nearly confluent pattern was sufficient for complete regression of ROP in laser group.Single IVB was appropriate for managing most of cases with ROP in bevacizumab group,but a small proportion(nearly one tenth)of them had recurrent episodes requiring adjuvant therapies.展开更多
Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-...Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were identified.Results: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed(12.3 vs. 4.8 vs. 8.6 months;P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy.Conclusions: First-line induction and maintenance therapy with Bev(7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.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
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
AIM: To compare visual acuity and central macular thickness(CMT) changes in neovascular age-related macular degeneration patients treated with either 6weekly bevacizumab regimen or 4 weekly ranibizumab on an as req...AIM: To compare visual acuity and central macular thickness(CMT) changes in neovascular age-related macular degeneration patients treated with either 6weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis.·METHODS: Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits.Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on the reduction of 〉5 letters in the best-corrected visual acuity(BCVA), the presence of retinal fluid on optical coherence tomography(OCT) or new retinal haemorrhage.·RESULTS: Visual acuity at 2y bevacizumab patients gained 7. 0 letters and ranibizumab 9. 2( P = 0. 31, 95 %CI-6.4 to 2.0). At 2y 86% of bevacizumab and 94%ranibizumab patients had not lost 15 letters or more(P =0.13). Mean CMT decreased at 2y bevacizumab by 146 μm,ranibizumab 160 μm(P =0.72). Mean number of injections was at 2y bevacizumzb 11.9, ranibizumab 10.3(P =0.023).· CONCLUSION: Bevacizumab 6 weekly on an as required basis was not demonstrably non-inferior to ranibizumab 4 weekly pro re nata(prn) in terms of BCVA and change in CMT. In the bevacizumab group, one more injection was required in the second year compared to the ranibizumab group.展开更多
Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP ...Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.展开更多
Glioblastoma multiforme(GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology andmedicine. Historically this may be contextualized in the f...Glioblastoma multiforme(GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology andmedicine. Historically this may be contextualized in the fact that the medical and scientific communities have had a very elementary understanding of its intricate and complex pathophysiology. The last 10-15 years have yielded a number of studies that have elucidated much of the molecular and genetic complexities of GBM that underlie its pathogenesis. Excitingly, some of these discovered genetic mutations and molecular profiles in GBM have demonstrated value in prognostication and utility in predicting response to treatment. Despite this, however, treatment options for patients have remained somewhat limited. These treatment options are expected to expand with the availability of new data and with the transition of novel treatment modalities from animal to human studies. This paper will have a threefold objective: provide an overview of the traditional paradigm in understanding and treating GBM, describe recent discoveries in the molecular pathogenesis of GBM against this historical backdrop, and acquaint the reader with new treatment modalities that hold significant therapeutic potential for patients.展开更多
Treatment of the wet form of age-related macular degeneration(wet AMD) has been revolutionized a decade ago with the introduction of vascular endothelial growth factor(VEGF) blockers that reduce neovascularization and...Treatment of the wet form of age-related macular degeneration(wet AMD) has been revolutionized a decade ago with the introduction of vascular endothelial growth factor(VEGF) blockers that reduce neovascularization and macular edema. Two approved drugs are marketed for the treatment of wet AMD—ranibizumab and aflibercept, but there is a third drug, bevacizumab, which is widely used offlabel; a cancer drug that also blocks VEGF but was never tested in pivotal trials and never approved for ophthalmic indications including wet AMD. Similarity of bevacizumab to ranibizumab led to off-label use and even to government-sponsored studies comparison the approved ranibizumab head-to-head to the offlabel cancer drug bevacizumab in wet AMD, like the Comparison of Age-related Macular Degeneration Treatments Trials(CATT) study, discussed in this perspective paper. Recent publication of 5-year follow-up from the initial 2-year CATT study provided the occasion to discuss the similarities and differences between these two drugs and the lessons learned from the last decade of anti-VEGF therapy for wet AMD. Clinical efficacy is comparable, with an advantage for ranibizumab. Likewise, safety finding favor ranibizumab over bevacizumab in some aspects. The latest addition of approved anti-VEGF drugs for wet AMD, aflibercept, may provide even more benefit to patients. In this perspective we discuss results of CATT and other longterm follow-up and comparative studies. While all demonstrate clinical benefit of anti-VEGF, all reveal that most patients' loose visual acuity(VA) in real-life situations over 5–7 years. This loss is based on—what we believe—significant under-treatment of wet AMD patients, due to economic or practical limitations and overestimation of perceived risks as geographic atrophy. We compare own data that showed more intensive treatment(more than twice the CATT-follow-up injections) with ranibizumab or aflibercept can maintain a sustained gain in VA in wet AMD patients after 6 years. We encourage retina specialists to treat wet AMD patients more aggressively and frequently in order to provide the maximum benefit for their patients.展开更多
文摘Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.
文摘Objective The aim of this study was to assess the value of palliative local treatment of incurable metastatic lesions in colorectal cancer(CRC) patients receiving chemotherapy plus bevacizumab.Methods Data of 105 patients with histologically confirmed synchronous or metachronous metastatic CRC who received bevacizumab treatment from January 1, 2011 to January 31, 2017 were retrospectively reviewed. Sixteen(15%) patients who were treated with bevacizumab for less than 4 cycles were excluded, and finally, 89(85%) patients were enrolled. Among them, 33(37%) patients who received palliative local treatment were categorized into the palliative local treatment group, and the remaining 56(63%) patients were categorized into the chemotherapy plus bevacizumab group. The primary endpoint was overall survival(OS), which was calculated using Kaplan-Meier survival analyses. Factors possibly influencing survival were evaluated by univariate and multivariate analyses. Adverse events(AEs) were graded according to Common Terminology Criteria for Adverse Events, version 4.0. Grades 1–2 and 3–4 AEs of the two groups were compared and analyzed using the Fisher's exact test and χ~2 analysis.Results The median follow-up period was 20.4 months, ranging from 1 to 60 months. The median OS in the palliative local treatment group was 36.3 months(95% CI, 33.5–39.2), and that in the chemotherapy plus bevacizumab group was 20.5 months(95% CI, 17.6–23.4). Both the univariate(HR 0.13, 95% CI, 0.05–0.30, P < 0.001) and multivariate(HR 0.16, 95% CI, 0.07–0.39, P < 0.001) analyses showed that the addition of palliative local treatment could prolong survival compared with chemotherapy plus bevacizumab alone. There were no significant differences in the rates of common chemotherapy-or bevacizumab-related AEs between the two groups.Conclusion These findings suggest palliative local treatment is an effective and safe method for treating patients with incurable metastatic CRC receiving chemotherapy plus bevacizumab.
文摘AIM: To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor(VEGF) treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor(VEGFR) expressions were evaluated following repeated bevacizumab treatments in hypoxic human umbilical vein endothelial cells(HUVECs) in vitro.METHODS: HUVECs were incubated under hypoxic conditions in two media of different bevacizumab concentrations(1.0 or 2.5 mg/m L) for 17 h, and then in a new medium without bevacizumab for 7h. This procedure was repeated twice more. A culture with an identical volume of excipients served as the control. Cytotoxicity and cell proliferation were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and Ki-67 assays, respectively. Levels of VEGF and VEGFR were assessed using enzyme-linked immunosorbent assay and Western blot respectively.RESULTS: Cytotoxic effects were not reported for either bevacizumab concentration. Cell proliferation was not reduced after anti-VEGF treatments. VEGF level after single treatment was significantly higher than that of the control and after repeated treatments. Phosphorylated VEGFR-2 expression increased significantly after singleand repeated bevacizumab treatments compared with the control. The 1.0 mg/m L bevacizumab induced significantly higher expressions of VEGFR-2 than the 2.5 mg/m L in single and repeated treatment groups.CONCLUSION: Bevacizumab treatment of HUVECs elevated VEGFR expression in both single and repeated treatments, indicating a mechanism for the reduced efficacy of anti-VEGF therapy in ocular neovascular disorders.
文摘Background:To compare the structural outcome of intravitreal bevacizumab(IVB)and laser treatment for type 1 retinopathy of prematurity(ROP).Methods:This is a retrospective comparative study.From December 2002 to April 2009,patients with type 1ROP according to criteria of Early Treatment of Retinopathy of Prematurity(ETROP)study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern.From May 2009 to January 2015,we performed IVB for patients with type 1 ROP.The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group.The demographical data,postmenstrual age(PMA)for treatment,and fundus findings were recorded by chart review.The difference between laser and bevacizumab groups was compared by Student t-test and Fisher exact test.Results:We collected 43 patients(86 eyes)with type 1 ROP,including 30 male and 13 female infants.Their mean gestation age and birth body weight(BBW)were 27.5 weeks and 1,034 gm.Zone I and zone II disease were found in 8 and 35 patients.The mean PMA for treatment was 37.3 weeks.The mean follow-up period was54.4 months.Laser treatment was administered in 26 patients,and bevacizumab injection for 17 infants.Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization.Complete regression of ROP was found in 15 infants of bevacizumab group following the first IVB.Four eyes in two patients(2/17,11.7%)had recurrence of ROP and received additional injections and adjuvant laser treatment.There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management.Conclusions:Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes.Single session of laser ablation in nearly confluent pattern was sufficient for complete regression of ROP in laser group.Single IVB was appropriate for managing most of cases with ROP in bevacizumab group,but a small proportion(nearly one tenth)of them had recurrent episodes requiring adjuvant therapies.
基金supported by Wu Jieping Fund (No. 320.6750.14266)
文摘Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were identified.Results: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed(12.3 vs. 4.8 vs. 8.6 months;P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy.Conclusions: First-line induction and maintenance therapy with Bev(7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.
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.
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.
文摘AIM: To compare visual acuity and central macular thickness(CMT) changes in neovascular age-related macular degeneration patients treated with either 6weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis.·METHODS: Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits.Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on the reduction of 〉5 letters in the best-corrected visual acuity(BCVA), the presence of retinal fluid on optical coherence tomography(OCT) or new retinal haemorrhage.·RESULTS: Visual acuity at 2y bevacizumab patients gained 7. 0 letters and ranibizumab 9. 2( P = 0. 31, 95 %CI-6.4 to 2.0). At 2y 86% of bevacizumab and 94%ranibizumab patients had not lost 15 letters or more(P =0.13). Mean CMT decreased at 2y bevacizumab by 146 μm,ranibizumab 160 μm(P =0.72). Mean number of injections was at 2y bevacizumzb 11.9, ranibizumab 10.3(P =0.023).· CONCLUSION: Bevacizumab 6 weekly on an as required basis was not demonstrably non-inferior to ranibizumab 4 weekly pro re nata(prn) in terms of BCVA and change in CMT. In the bevacizumab group, one more injection was required in the second year compared to the ranibizumab group.
文摘Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.
文摘Glioblastoma multiforme(GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology andmedicine. Historically this may be contextualized in the fact that the medical and scientific communities have had a very elementary understanding of its intricate and complex pathophysiology. The last 10-15 years have yielded a number of studies that have elucidated much of the molecular and genetic complexities of GBM that underlie its pathogenesis. Excitingly, some of these discovered genetic mutations and molecular profiles in GBM have demonstrated value in prognostication and utility in predicting response to treatment. Despite this, however, treatment options for patients have remained somewhat limited. These treatment options are expected to expand with the availability of new data and with the transition of novel treatment modalities from animal to human studies. This paper will have a threefold objective: provide an overview of the traditional paradigm in understanding and treating GBM, describe recent discoveries in the molecular pathogenesis of GBM against this historical backdrop, and acquaint the reader with new treatment modalities that hold significant therapeutic potential for patients.
文摘Treatment of the wet form of age-related macular degeneration(wet AMD) has been revolutionized a decade ago with the introduction of vascular endothelial growth factor(VEGF) blockers that reduce neovascularization and macular edema. Two approved drugs are marketed for the treatment of wet AMD—ranibizumab and aflibercept, but there is a third drug, bevacizumab, which is widely used offlabel; a cancer drug that also blocks VEGF but was never tested in pivotal trials and never approved for ophthalmic indications including wet AMD. Similarity of bevacizumab to ranibizumab led to off-label use and even to government-sponsored studies comparison the approved ranibizumab head-to-head to the offlabel cancer drug bevacizumab in wet AMD, like the Comparison of Age-related Macular Degeneration Treatments Trials(CATT) study, discussed in this perspective paper. Recent publication of 5-year follow-up from the initial 2-year CATT study provided the occasion to discuss the similarities and differences between these two drugs and the lessons learned from the last decade of anti-VEGF therapy for wet AMD. Clinical efficacy is comparable, with an advantage for ranibizumab. Likewise, safety finding favor ranibizumab over bevacizumab in some aspects. The latest addition of approved anti-VEGF drugs for wet AMD, aflibercept, may provide even more benefit to patients. In this perspective we discuss results of CATT and other longterm follow-up and comparative studies. While all demonstrate clinical benefit of anti-VEGF, all reveal that most patients' loose visual acuity(VA) in real-life situations over 5–7 years. This loss is based on—what we believe—significant under-treatment of wet AMD patients, due to economic or practical limitations and overestimation of perceived risks as geographic atrophy. We compare own data that showed more intensive treatment(more than twice the CATT-follow-up injections) with ranibizumab or aflibercept can maintain a sustained gain in VA in wet AMD patients after 6 years. We encourage retina specialists to treat wet AMD patients more aggressively and frequently in order to provide the maximum benefit for their patients.