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  1. Qin S, Chen M, Cheng AL, Kaseb AO, Kudo M, Lee HC, et al.
    Lancet, 2023 Nov 18;402(10415):1835-1847.
    PMID: 37871608 DOI: 10.1016/S0140-6736(23)01796-8
    BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.

    METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098.

    FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.

    INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.

    FUNDING: F Hoffmann-La Roche/Genentech.

    Matched MeSH terms: Bevacizumab/therapeutic use
  2. Alisa-Victoria K, Jin-Poi T, Shatriah I, Zunaina E, Ngah NF
    Clin Ophthalmol, 2014;8:537-42.
    PMID: 24648718 DOI: 10.2147/OPTH.S55623
    Best's vitelliform macular dystrophy complicated with choroidal neovascularization is rare in children. We report three children from a Malay family of five siblings with Best's vitelliform macular dystrophy, in which two of them subsequently developed choroidal neovascularization. The possible pathogenesis of this rare condition is described and highlighted in this report.
    Matched MeSH terms: Bevacizumab
  3. Zhukova N, Rajagopal R, Lam A, Coleman L, Shipman P, Walwyn T, et al.
    Cancer Med, 2019 01;8(1):40-50.
    PMID: 30569607 DOI: 10.1002/cam4.1799
    In pediatric low-grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low-toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow-up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment-limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.
    Matched MeSH terms: Bevacizumab/administration & dosage*; Bevacizumab/adverse effects
  4. Chellappan DK, Leng KH, Jia LJ, Aziz NABA, Hoong WC, Qian YC, et al.
    Biomed Pharmacother, 2018 Jun;102:1127-1144.
    PMID: 29710531 DOI: 10.1016/j.biopha.2018.03.061
    OBJECTIVE: The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers.

    METHODS: The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review.

    RESULTS: In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents.

    CONCLUSION: Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers.

    Matched MeSH terms: Bevacizumab/pharmacology; Bevacizumab/therapeutic use*
  5. Teo, B.H., Safinaz, M.K., Mae-Lynn, C.B., Amin, A., Edward, R., Mushawiahti, M.
    Medicine & Health, 2018;13(2):175-179.
    MyJurnal
    It is rare for anterior chamber migration of an Ozurdex® implant from vitreous cavity, but it is seen more frequently in aphakic eyes or in pseudophakic cases with zonular dehiscense. We describe a case of a middle-aged gentleman who had persistent diabetic macular oedema not responding to anti-VEGF (vascular endothelium growth factor), who was treated with intravitreal Ozurdex® in his post vitrectomized eye and developed anterior migration of the implant to the anterior chamber. Anterior dislocation of an intravitreal implant of dexamethasone can be managed by repositioning it to the vitreous cavity or removing it through a corneal limbal incision. Ozurdex® is a friable implant, especially after a few weeks of implantation. Therefore, removal of the implant by grasping or aspiration may lead to its fracture or dispersion of the implant material. This is a report of a simple,fast and effective technique to remove a migrated Ozurdex® from the anterior chamber using a modified silicone tip.
    Matched MeSH terms: Bevacizumab
  6. Ab Mutalib NS, Md Yusof NF, Abdul SN, Jamal R
    Front Pharmacol, 2017;8:736.
    PMID: 29075194 DOI: 10.3389/fphar.2017.00736
    Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years. However, the side effects of systemic therapy such as toxicity may cause fatal complications and have a major consequences on the patients' quality of life. Hence, there is an urgent need for key biomarkers which will enable the selection of optimal drug singly or in combination for an individual patient. The application of personalized therapy based on DNA testing could aid the clinicians in providing the most effective chemotherapy agents and dose modifications for each patient. Yet, some of the current findings are controversial and the evidences are conflicting. This review aims at summarizing the current state of knowledge about germline pharmacogenomics DNA variants that are currently used to guide therapeutic decisions and variants that have the potential to be clinically useful in the future. In addition, current updates on germline variants conferring treatment sensitivity, drug resistance to existing chemotherapy agents and variants affecting prognosis and survival will also be emphasized. Different alteration in the same gene might confer resistance or enhanced sensitivity; and while most of other published reviews generally stated only the gene name and codon location, we will specifically discuss the exact variants to offer more accurate information in this mini review.
    Matched MeSH terms: Bevacizumab
  7. Dranitsaris G, Truter I, Lubbe MS, Sriramanakoppa NN, Mendonca VM, Mahagaonkar SB
    Malays J Med Sci, 2011 Oct;18(4):32-43.
    PMID: 22589671 MyJurnal
    Decision analysis (DA) is commonly used to perform economic evaluations of new pharmaceuticals. Using multiples of Malaysia's per capita 2010 gross domestic product (GDP) as the threshold for economic value as suggested by the World Health Organization (WHO), DA was used to estimate a price per dose for bevacizumab, a drug that provides a 1.4-month survival benefit in patients with metastatic colorectal cancer (mCRC).
    Matched MeSH terms: Bevacizumab
  8. Jirjees F, Soliman K, Wang Y, Sonawane R, Sheshala R, Jones D, et al.
    J Pharm Biomed Anal, 2019 Sep 10;174:145-150.
    PMID: 31167158 DOI: 10.1016/j.jpba.2019.05.038
    Bevacizumab is a full-length human monoclonal antibody used to treat various neovascular diseases such as wet age-related macular degeneration (AMD), diabetic eye disease and other problems of the retina. Monthly intravitreal injections of bevacizumab (Avastin®) are effective in the treatment of wet AMD. However, there is a growing demand in the development of sustained release ophthalmic formulations. Therefore, this study aims, for the first time, to develop a rapid, simple, and sensitive method using size exclusion chromatography coupled with fluorescence detection for routine quantification of bevacizumab in ophthalmic formulations and during in vitro release studies. The selected chromatographic conditions included an aqueous mobile phase composed of 35 mM sodium phosphate buffer and 300 mM sodium chloride (pH 6.8), a flow rate of 0.5 mL/min, and the fluorescence detector was operated at excitation and emission wavelengths of 280 and 340 nm, respectively. The peak area-concentration relationship maintained its linearity over concentration range of 0.1-20 μg/mL (R2 = 0.9993), and the quantitation limit was 100 ng/mL. The method was validated for specificity, accuracy, precision, and robustness. The developed method had a run time of 6 min at temperature 25 °C, making it a unique validated method for rapid and cost-effective quantification of bevacizumab.
    Matched MeSH terms: Bevacizumab/analysis*
  9. Sakamoto T, Shimura M, Kitano S, Ohji M, Ogura Y, Yamashita H, et al.
    Graefes Arch Clin Exp Ophthalmol, 2022 Feb;260(2):477-487.
    PMID: 34477927 DOI: 10.1007/s00417-021-05308-8
    PURPOSE: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis.

    METHODS: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS).

    RESULTS: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080).

    CONCLUSION: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

    Matched MeSH terms: Bevacizumab/therapeutic use
  10. Yong MH, Amin A, Mushawiahti M, Bastion ML
    Med J Malaysia, 2015 Dec;70(6):358-60.
    PMID: 26988210
    We report a case of a middle-aged gentleman with recalcitrant macular oedema (RMO) secondary to ischaemic central retinal vein occlusion (CRVO). He was given six injections of intravitreal ranibizumab (anti-VEGF) monthly. However, his visual acuity (VA) deteriorated and the macular oedema worsened. He then received an intravitreal dexamethasone implant eight months post-CRVO. His VA and macular oedema improved dramatically and significantly at first follow-up and remained stable at six months after implant. This case can be a reference for those who treating recalcitrant macular oedema. It shows the effect of an intravitreal dexamathasone implant might have in a patient with RMO due to CRVO. The patient enjoyed improvement of vision, with clinical evidence of reduction in central macular thickness (CMT) and with no serious adverse events after a single injection up to six months post implant.
    Matched MeSH terms: Bevacizumab
  11. Daftarian N, Zandi S, Piryaie G, Nikougoftar Zarif M, Ranaei Pirmardan E, Yamaguchi M, et al.
    FASEB J, 2020 Jun;34(6):8001-8011.
    PMID: 32333612 DOI: 10.1096/fj.201901902RR
    Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P 
    Matched MeSH terms: Bevacizumab
  12. Eteraf-Oskouei T, Allahyari S, Akbarzadeh-Atashkhosrow A, Delazar A, Pashaii M, Gan SH, et al.
    PMID: 25977699 DOI: 10.1155/2015/760405
    The antiangiogenesis effect of Ficus carica leaves extract in an air pouch model of inflammation was investigated in rat. Inflammation was induced by injection of carrageenan into pouches. After antioxidant capacity and total phenolic content (TPC) investigations, the extract was administered at 5, 25, and 50 mg/pouch, and then the volume of exudates, the cell number, TNFα, PGE2, and VEGF levels were measured. Angiogenesis of granulation tissues was determined by measuring hemoglobin content. Based on the DPPH assay, the extract had significant antioxidant activity with TPC of 11.70 mg GAE/100 g dry sample. In addition, leukocyte accumulation and volume of exudate were significantly inhibited by the extract. Moreover, it significantly decreased the production of TNFα, PGE2, and VEGF, while angiogenesis was significantly inhibited by all administered doses. Interestingly, attenuation of angiogenesis and inflammatory parameters (except leukocyte accumulation) by the extract was similar to that shown by diclofenac. The extract has anti-inflammatory effects and ameliorated cell influx and exudation to the site of the inflammatory response which may be related to the local inhibition of TNFα, PGE2, and VEGF levels as similarly shown by diclofenac. The antiangiogenesis and anti-VEGF effects of Ficus carica may be correlated with its significant antioxidant potentials.
    Matched MeSH terms: Bevacizumab
  13. Oon CE, Bridges E, Sheldon H, Sainson RCA, Jubb A, Turley H, et al.
    Oncotarget, 2017 Jun 20;8(25):40115-40131.
    PMID: 28445154 DOI: 10.18632/oncotarget.16969
    Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro. Mouse DLL4 or JAG1 expressed in glioblastoma cells decreased tumour cell proliferation in vitro but promoted tumour growth in vivo. mDLL4-expressing tumours showed fewer but larger vessels whereas mJAG1-tumours produced more vessels. In both tumour types pericyte coverage was decreased but the vessels were more perfused. Both ligands increased tumour resistance towards anti-VEGF therapy but the resistance was higher in mDLL4-tumours versus mJAG1-tumours. However, their sensitivity to the therapy was restored by blocking Notch signalling with dibenzazepine. Importantly, anti-DLL4 antibody blocked the effect of JAG1 on tumour growth and increased vessel branching in vivo. The mechanism behind the differential responsiveness was due to a positive feedback loop for DLL4-Notch signalling, rendering DLL4 more dominant in activating Notch signalling in the tumour microenvironment. We concluded that DLL4 and JAG1 promote tumour growth by modulating tumour angiogenesis via different mechanisms. JAG1 is not antagonistic but utilises DLL4 in tumour angiogenesis. The results suggest that anti-JAG1 therapy should be explored in conjunction with anti-DLL4 treatment in developing anti-Notch therapies in clinics.
    Matched MeSH terms: Bevacizumab/pharmacology
  14. Subrayan V, Khaw KW, Peyman M, Koay AC, Tajunisah I
    Ophthalmologica, 2013;229(4):208-11.
    PMID: 23548379 DOI: 10.1159/000348630
    To evaluate the outcome of intravitreal bevacizumab in the treatment of radiation-induced cystoid macular oedema among patients who underwent external beam radiotherapy for nasopharyngeal carcinoma.
    Matched MeSH terms: Bevacizumab
  15. Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.
    Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
    PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004
    Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.
    Matched MeSH terms: Bevacizumab
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