Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators.     

2019—2021年天津市人民医院贝伐珠单抗临床应用合理性分析

目的 对2019—2021年天津市人民医院贝伐珠单抗的临床应用情况进行评价,以期促进贝伐珠单抗超说明书用药的管理及其临床合理应用。方法 回顾性分析天津市人民医院2019年1月—2021年12月使用贝伐珠单抗患者的用药信息,根据说明书及指南评价其应用的合理性。结果 共收集1 313例患者（6 134次医嘱）,通过适应症、治疗方案、用法用量3个方面评价应用合理性。结果 显示,存在适应症不适宜情况占比0.07%,用法用量不适宜情况占比4.77%,其中包括给药浓度不适宜（1.21%）、给药途径不适宜（0.23%）、与手术间隔时间不适宜（3.33%）。结论 天津市人民医院贝伐珠单抗的临床应用基本符合国内外说明书及指南要求,但也存在一定的超说明书用药情况。医院及临床药师应持续规范抗肿瘤药物超说明书使用的管理,促进抗肿瘤药物的合理应用。     

Intravitreal bevacizumab injection for chronic central serous chorioretinopathy

Abstract Purpose: To evaluate the safety and efficacy of intravitreal bevacizumab injection for the treatment of chronic central serous chorioretinopathy. Methods: There eyes of 3 patients with chronic central serous chorioretinopathy received an intravitreal bevacizumab 0.1ml (2.5mg) injection. Observation procedures were best-corrected visual acuity(BCVA), fluorescein angiography(FA), and optical coherence tomography（OCT）. Results: All patients showed improved visual acuity, and reduced or resolved serous neuroepithelial detachment following treatment. Conclusions: Intravitreal bevacizumab injection resulted in improved visual acuity and anatomical results for chronic CSC with persistent serous neuroepithelial detachment. The results suggest that vascular endothelial growth factor (VEGF) may be involved in fluid leakage in patients with chronic CSC and a possible role for anti-VEGF agents in the treatment of chronic CSC. Further evaluation of intravitreal bevacizumab for chronic CSC is warranted. Key words Central serous chorioretinopathy, Intravitreal bevacizumab, Retinal pigment epithelium detachment     

Repeated bevacizumab injections versus mitomycin C in rotational conjunctival flap for prevention of pterygium recurrence

Aims:

To evaluate the efficacy of repeated bevacizumab injection in rotational conjunctival flap surgery versus rotational conjunctival flap with adjunctive mitomycin C (MMC) or rotational conjunctival flap alone.

Materials and Methods:

Ninety eyes of 90 patients who underwent primary pterygium surgery with rotational flap were evaluated. Patients were randomly assigned to undergo conjunctival rotational flap alone (Group A) or conjunctival rotational flap with either 0.02% MMC application (Group B) or adjunctive subconjunctival 2.5 mg/0.1 ml bevacizumab injection (Group C). Each group consisted of 30 eyes. Recurrence rates at 9 months were evaluated.

Results:

There were no statistically significant differences in mean size of the pterygium across the limbus in terms of length (P > 0.5). The recurrence rates at 9 months were 26.6% (n = 8) in Group A, 13.3% (n = 4) in Group B, and 10% (n = 3) in Group C. The recurrence rates in Group B and C were significantly lower than in Group A (P =0.1806). The recurrence rates were similar in Group B and C (P > 0.05).

Conclusions:

Subconjunctival bevacizumab injection may decrease the recurrence rate of primary pterygium surgery with rotational conjunctival flap. Further studies with a larger population and longer follow-up period are needed to supplement this study.     

贝伐单抗联合紫杉类化疗方案治疗HER-2阴性转移性乳腺癌的疗效评估:一项Meta分析

目的:采用Meta分析方法系统性评估贝伐单抗联合紫杉类化疗药物对HER-2阴性转移性乳腺癌的治疗效果。方法:电子计算机检索自建库至2020年12月发表的有关贝伐单抗联合紫杉类药物治疗HER-2阴性转移性乳腺癌的文章。根据制定的纳入和排除标准对文献进行筛选以及质量评价,然后提取研究数据。选择PFS、OS、ORR以及1年生存率（1y SR）作为主要疗效结局指标,采用Stata软件对合并效应量风险比率（hazard ratio,HR）和相对危险度（relative ratio,RR）进行Meta合并分析,按照研究类型进行亚组分析。发表偏倚利用漏斗图法以及Egger检验进行定性和定量评估。结果:初检文献849篇,最终纳入9篇文献进入Meta分析,研究共包含患者6 242例,其中贝伐单抗联合紫杉组3 555例,紫杉单药组2 687例。文献质量评价均为中等或高等质量。Meta合并结果显示,贝伐单抗联合紫杉方案对比紫杉单药能够显著提升PFS（HR=0.65,95%CI 0.55~0.77,Z=5.01,P＜0.001）、ORR（RR=1.59,95%CI 1.44~11.74,Z=9.61,P＜0.001）以及1y SR（RR=1.11,95%CI 1.08~1.15,Z=6.26,P＜0.001）,但在OS方面的优势不具有显著统计学意义（HR=0.83,95%CI 0.69~1.00,Z=2.0,P＜0.045）。结论:贝伐单抗联合紫杉类治疗方案,相比紫杉单药化疗方案可以明显提升PFS、ORR以及1年生存率,但并不能显著增加OS。因此,在临床实践中,应当谨慎选择化疗方案。     

A Comparison of Folinic Acid,Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer

AimTo compare the efficacy and safety of folinic acid, fluorouracil and irinotecan (FOLFIRI) plus bevacizumab or aflibercept in metastatic colorectal cancer (mCRC) patients pretreated with oxaliplatin-based chemotherapy.Materials and methodsWe analysed the treatment outcomes of patients receiving FOLFIRI in combination with bevacizumab or aflibercept as second-line treatment for mCRC between October 2017 and March 2020. This analysis included 67 patients receiving FOLFIRI plus aflibercept and 83 receiving FOLFIRI plus bevacizumab.ResultsThe overall response rate (ORR) was 13.6% (95% confidence interval 4.85–22.34) in the FOLFIRI–aflibercept group and 14.7% (95% confidence interval 6.68–22.71) in the FOLFIRI–bevacizumab group. This difference in ORR was not statistically significant. The median progression-free survival was 8.6 months in the FOLFIRI–bevacizumab group and 8.5 months in the FOLFIRI–aflibercept group (P = 0.752). Patients in the FOLFIRI–bevacizumab group showed a median overall survival of 12.4 months, whereas patients in the FOLFIRI–aflibercept group had a median overall survival of 13.7 months (P = 0.276). There were no significant differences in survival between the two treatment groups. The adverse events were also largely similar between the two groups. However, hypertension of grade 3 or more was more frequent in the FOLFIRI–aflibercept group.ConclusionFOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumour activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC.     

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis

Background What benefits and toxicities patients acquire from the use of bevacizumab combined with first-line chemotherapy remains controversial.This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer （mCRC）.Methods Several databases,including PubMed,Embase,and Cochrane Library,were searched up to April 30,2013.Eligible studies were only randomized,controlled trials （RCTs） with a direct comparison between mCRC patients treated with and without bevacizumab.Overall risk ratio （RR）,hazard ratio （HR）,odds ratio （OR）,and 95％ confidence intervals （CO were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials.Results Six RCTs,including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group,were included.Overall,the addition of bevacizumab to first-line chemotherapy increased overall response rate （ORR） by 4.5％,prolonged both progression-free survival （PFS） and overall survival （OS）,and increased the rate of total Grades 3 or 4 adverse events （G3/4AEs） by 6.9％.Significant differences were found in ORR （RR=1.22 （95％ CI 1.01-1.46）,P=0.03）,PFS （HR=0.60 （95％ Cl 0.47-0.77）,P ＜0.0001）,OS （HR=0.83 （95％ Cl 0.70-0.97）,P=0.02）,and any G3/4AEs （OR=1.56 （95％ Cl 1.29-1.89）,P ＜0.00001）.Conclusion Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC,because of conferring a significant improvement in ORR,PFS,and OS,even though it increased adverse events.