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Journal of Translational Medicine Jan 2020Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint...
BACKGROUND
Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint inhibitors has provided promising results, most patients with advanced melanoma are resistant to these treatments and develop severe side effects. Novel treatment strategies are needed for patients with meningeal melanoma metastases, and the potential of antiangiogenic therapy was investigated in this preclinical study.
METHODS
Two GFP-transfected melanoma models (A-07 and D-12) differing substantially in VEGF-A expression were included in the study, and the anti-VEGF-A antibody bevacizumab was used as therapeutic agent. Meningeal metastases were initiated in BALB/c nu/nu mice by intracranial inoculation of melanoma cells, and bevacizumab treatment was given twice a week in i.p. doses of 10 mg/kg until the mice became moribund. Therapeutic effects were evaluated by determining tumor host survival time, assessing tumor growth and angiogenic activity by quantitative analyses of histological preparations, and measuring the expression of angiogenesis-related genes by quantitative PCR.
RESULTS
Meningeal A-07 melanomas showed higher expression of VEGF-A than meningeal D-12 melanomas, whereas the expression of ANGPT2 and IL8, two important angiogenesis drivers in melanoma, was much higher in D-12 than in A-07 tumors. Bevacizumab treatment inhibited tumor angiogenesis and prolonged host survival in mice with A-07 tumors but not in mice with D-12 tumors. Meningeal A-07 tumors in bevacizumab-treated mice compensated for the reduced VEGF-A activity by up-regulating a large number of angiogenesis-related genes, including ANGPT2 and its receptors TIE1 and TIE2. Melanoma cells migrated from meningeal tumors into the cerebrum, where they initiated metastatic growth by vessel co-option. In the A-07 model, the density of cerebral micrometastases was higher in bevacizumab-treated than in untreated mice, either because bevacizumab treatment increased mouse survival or induced increased tumor gene expression.
CONCLUSIONS
The development of antiangiogenic strategies for the treatment of meningeal melanoma metastases is a challenging task because the outcome of treatment will depend on the angiogenic signature of the tumor tissue, treatment-induced alterations of the angiogenic signature, and the treatment sensitivity of metastatic lesions in other intracranial sites.
Topics: Adult; Angiogenesis Inhibitors; Animals; Bevacizumab; Female; Humans; Melanoma; Meningeal Neoplasms; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
PubMed: 31915016
DOI: 10.1186/s12967-020-02212-3 -
Molecules (Basel, Switzerland) Jul 2021Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process.... (Review)
Review
Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.
Topics: Animals; Antineoplastic Agents, Immunological; Bevacizumab; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms
PubMed: 34299401
DOI: 10.3390/molecules26144127 -
Expert Review of Anticancer Therapy Aug 2011Current targeted strategies for cancer focus on the blockade of growth factor receptors and the inhibition of angiogenesis. The VEGF pathway has become an attractive... (Review)
Review
Current targeted strategies for cancer focus on the blockade of growth factor receptors and the inhibition of angiogenesis. The VEGF pathway has become an attractive target in multiple malignancies, including lung cancer. Bevacizumab, a monoclonal antibody against VEGF, increased survival in non-small-cell lung cancer (NSCLC) patients when added to standard carboplatin/paclitaxel chemotherapy. The pivotal Phase III study (ECOG 4599) in NSCLC showed longer overall survival: 12.3 versus 10.3 months and a higher median progression-free survival of 6.2 versus 4.5 months when chemotherapy was associated with bevacizumab. Benefits were confirmed in terms of progression-free survival in the European Phase III study (AVAiL). Subsequently, bevacizumab gained US FDA and European Medicines Agengy approval as a first-line therapy for advanced NSCLC. Bevacizumab's safety profile is well established: most adverse events are mild to moderate and can be managed using standard interventions. This article presents an overview of the current data on bevacizumab for NSCLC.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Humans; Lung Neoplasms; Treatment Outcome
PubMed: 21916570
DOI: 10.1586/era.11.80 -
Eye (London, England) Apr 2019
Topics: Angiogenesis Inhibitors; Bevacizumab; Humans; Macular Degeneration
PubMed: 30482906
DOI: 10.1038/s41433-018-0281-2 -
Future Oncology (London, England) Feb 2023SB8 is a biosimilar of bevacizumab based on its similarity demonstrated by physicochemical, functional, non-clinical and clinical studies. Supported by the concept of... (Review)
Review
SB8 is a biosimilar of bevacizumab based on its similarity demonstrated by physicochemical, functional, non-clinical and clinical studies. Supported by the concept of extrapolation, SB8 was authorized and is used in a similar manner across all types of tumors as reference bevacizumab. Furthermore, SB8 offers convenience with prolonged stability compared with reference bevacizumab in diluted form. Although a biosimilar must demonstrate biosimilarity to a reference product with the 'totality of evidence' in a stringent regulatory process for marketing authorization, some concerns remain among healthcare practitioners, particularly about extrapolation. This review summarizes the concepts of the totality of evidence and extrapolation in biosimilar development and the role of bevacizumab biosimilars in the management of metastatic colorectal cancer as an extrapolated indication.
Topics: Humans; Bevacizumab; Biosimilar Pharmaceuticals; Drug Approval; Colonic Neoplasms; Rectal Neoplasms
PubMed: 36883661
DOI: 10.2217/fon-2022-1273 -
Eye (London, England) May 2022
Topics: Angiogenesis Inhibitors; Bevacizumab; Humans; Retina
PubMed: 35046548
DOI: 10.1038/s41433-021-01909-z -
Drug Design, Development and Therapy 2015Bevacizumab is the first molecular-targeted agent to be used for the treatment of ovarian cancer. Bevacizumab is a humanized monoclonal antibody targeting vascular... (Review)
Review
Bevacizumab is the first molecular-targeted agent to be used for the treatment of ovarian cancer. Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor. Two randomized Phase III trials evaluated the combination of bevacizumab plus standard cytotoxic chemotherapy for first-line treatment of advanced ovarian cancer. Additional Phase III trials evaluated bevacizumab combined with cytotoxic chemotherapy in platinum-sensitive and platinum-resistant recurrent ovarian cancer. All these trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, bevacizumab effectively improved the quality of life with regard to abdominal symptoms in recurrent ovarian cancer patients. Bevacizumab is associated with adverse events not commonly observed with cytotoxic agents used to treat gynecological cancers, such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed by gynecologists. The clinical trial results with bevacizumab have supported its recent approval in Europe and the United States as a treatment for ovarian cancer. This review presents the latest evidence for bevacizumab therapy of ovarian cancer and describes selection of patients for personalized treatment.
Topics: Animals; Antineoplastic Agents; Bevacizumab; Biomarkers, Tumor; Clinical Trials, Phase III as Topic; Female; Humans; Ovarian Neoplasms; Predictive Value of Tests; Randomized Controlled Trials as Topic
PubMed: 25960638
DOI: 10.2147/DDDT.S83275 -
Cancer Journal (Sudbury, Mass.) 2018
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Immunological; Bevacizumab; Humans; Mice; Neoplasms
PubMed: 30119078
DOI: 10.1097/PPO.0000000000000325 -
The Oncologist Feb 2015Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect.... (Review)
Review
Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events.
Topics: Angiogenesis Inhibitors; Bevacizumab; Disease Management; Glioblastoma; Humans; Venous Thromboembolism
PubMed: 25568148
DOI: 10.1634/theoncologist.2014-0330 -
Current Drug Targets 2017Ovarian cancer is the leading cause of deaths attributable to gynecologic malignancies. Late diagnosis and a high tendency of metastasis and drug resistance often lead... (Review)
Review
BACKGROUND
Ovarian cancer is the leading cause of deaths attributable to gynecologic malignancies. Late diagnosis and a high tendency of metastasis and drug resistance often lead to recurrence and poor outcomes. Anti-angiogenesis is considered a promising therapeutic strategy for recurrent ovarian cancers. Anti-VEGF body, bevacizumab, is an angiogenesis inhibitor with demonstrated activity and tolerable toxicity.
OBJECTIVE
To elucidate the benefits and side effects of bevacizumab for the therapy of recurrent ovarian cancer.
METHODS
Reviewed the results of published clinical trials.
RESULTS
Recent Phase II studies indicated that bevacizumab monotherapy or in combination with conventional or other anti-angiogenic chemotherapy reagents could be effective for recurrent (platinum- sensitive and -resistant) ovarian cancers. Additionally, two phase III randomized trials reached similar conclusions that in either platinum-sensitive or -resistant ovarian cancers, adding bevacizumab to chemotherapy can improve progression-free survival. Despite the general recognition of bevacizumab as a well-tolerated drug in recurrent ovarian cancer patients, oncologists have become aware of the significant risks associated with gastrointestinal perforation.
CONCLUSION
Bevacizumab used alone or combined with other chemotherapy reagents is efficacious and tolerable in the treatment of recurrent ovarian cancer.
Topics: Antineoplastic Agents, Immunological; Bevacizumab; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27138763
DOI: 10.2174/1389450117666160502150237