Practical Management of Bevacizumab-Related Toxicities in Glioblastoma

Brandes, Alba Ariela; Bartolotti, Marco; Tosoni, Alicia; Poggi, Rosalba; Franceschi, Enrico

doi:10.1634/theoncologist.2014-0330

Cited by 69 publications

(51 citation statements)

References 55 publications

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“…BH4 is in clinical trials for the treatment of endothelial dysfunction in a number of vascular diseases. Since the BH4/BH2 ratio of normal tissues is high and the NOS activity of these cells is coupled, BH4 or SP should have minimal effects on normal tissue and vasculature and is therefore a potentially safe alternative to other normalizing agents, such as avastin, which are associated with considerable toxicity (Brandes et al, 2015). Taken together, these findings show great promise for the use of SP as a vascular normalizing agent, and further investigation into NOS uncoupling and tumor vasculature is warranted.…”

Section: Discussionmentioning

confidence: 85%

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization

Rabender

Bruno

Alam

et al. 2018

J Pharmacol Exp Ther

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Previously, we demonstrated that nitric oxide (NO) synthase (NOS) is uncoupled in a wide range of solid tumors and that restoring NOS coupling with the tetrahydrobiopterin precursor sepiapterin (SP) inhibits tumor progression. Endothelial dysfunction characterizes the poorly functional vasculature of solid tumors, and since NO is critical for regulation of endothelial function we asked whether SP, by recoupling NOS, improves tumor vasculature structure and function-enhancing chemotherapeutic delivery and response to radiotherapy. MMTV-neu mice with spontaneous breast tumors were treated with SP by oral gavage and evaluated by multispectral optoacoustic tomographic analysis of tumor HbO and by tissue staining for markers of hypoxia, blood perfusion, and markers of endothelial and smooth muscle proteins. Recoupling tumor NOS activity results in vascular normalization observed as reduced tumor hypoxia, improved tumor percentage of HbO and perfusion, as well as increased pericyte coverage of tumor blood vessels. The normalized vasculature and improved tumor oxygenation led to a greater than 2-fold increase in radiation-induced apoptosis compared with radiation or SP alone. High-performance liquid chromatography analysis of tumor doxorubicin levels showed a greater than 50% increase in doxorubicin uptake and a synergistic effect on tumor cell apoptosis. This study highlights for the first time the importance of NOS uncoupling and endothelial dysfunction in the development of tumor vasculature and presents a new approach for improving the tumoricidal efficacies of chemotherapy and radiotherapy.

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Section: Discussionmentioning

confidence: 85%

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization

Rabender

Bruno

Alam

et al. 2018

J Pharmacol Exp Ther

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“…To minimize the risk of severe bleeding in the setting of bevacizumab therapy, it is imperative that patients be evaluated for potential risk factors for bleeding (27). Bevacizumab should not be administered to patients with serious hemorrhage or recent hemoptysis and should be discontinued upon development of any serious bleeding event.…”

Section: Bleeding Eventsmentioning

confidence: 99%

Biological agents in gastrointestinal cancers: adverse effects and their management

Arora¹,

Gupta²,

Singh³

2017

J. Gastrointest. Oncol.

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Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy. However, these agents bring with them a set of side effects attributable to their unique mechanisms of action. The anti VEGF agents-bevacizumab, aflibercept and ramucirumab, can result in renal and vascular complications such as hypertension, arterial thrombotic events (ATE), proteinuria and GI perforations. The anti EGFR agents classically cause dermatological toxicities, in addition to hypomagnesemia, which can be dose limiting for patients. Trastuzumab, a monoclonal antibody that targets Her2/Neu, is known to cause cardiotoxicity, especially when used with anthracyclines. Use of immunotherapy agents such as nivolumab is associated with the development immune related adverse events (irAEs). The use of these agents is expected to increase over the next few years and it is crucial that patients and practitioners are aware of their adverse effects and current management strategies. This review highlights the adverse events associated with the use of biologic and immunologic therapies in GI cancers, their incidence and current management strategies.

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“…Bevacizumab is a monoclonal antibody. It is a target for vascular endothelial growth factor (VEGF) receptor which works angiogenesis in cancer growth, and widely standard agents for several tumors [29] and has the possibility of being the root of maintenance therapy VEGF has been said not only tumoral angiogenesis but also several physiological engaging that involve vascular homeostasis, coagulation, wound healing, renal filtration, and blood pressure regulation. This molecular targeting drug has side effects such as Hypertension (HTN), Proteinuria, bleeding, venous thromboembolism (VTE) and spontaneous perforation of the gastrointestinal tract and so on.…”

Section: Discussionmentioning

confidence: 99%

Maintenance Therapy for Elderly Colorectal Cancer Patients with Bevacizumab: Single Center Experience

Orita¹,

Koshiba²,

Kushida³

et al. 2018

Cancer Sci Res

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Background: Over the past decade, the outcome of treatment with chemotherapy for metastatic colorectal cancer (mCRC) is substantially better, with proven increases survival. However, many patients still suffer significant toxicities, such as peripheral neuropathy. In advanced countries, where most patients with mCRC are older, maintenance therapy is under study with the goal of reducing severe side effects and maintaining quality of life (QOL). Continuation of cytotoxic chemotherapy in the setting of accumulated toxicities is often not feasible, so less toxic drugs are needed over the long-term. Bevacizumab is one option that has low side effects and proven benefit when combined with chemotherapy. This report describes our experience in giving bevacizumab maintenance therapy to 11 older patients with mCRC and reviews maintenance therapy for mCRC. Materials and Methods:Baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected from the local patient registry. Approval was provided by the Juntendo University Hospital Institutional Review Board. Results: Eleven patients received maintenance therapy after FOLFOX and/or FOLFIRI regimens for an average of 476 days. Maintenance therapy was instituted due to several side effects from oxaliplatin-based chemotherapy.Side effect included such as peripheral neuropathy and fatigue could reduce during maintenance therapy and get QOL until end stage.Conclusions: Our experience with these 11 patients, demonstrates both prolonged survival as well as maintained QOL. Bevacizumab based maintenance therapy may be considered in elderly patients with mCRC.

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Practical Management of Bevacizumab-Related Toxicities in Glioblastoma

Cited by 69 publications

References 55 publications

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization

Biological agents in gastrointestinal cancers: adverse effects and their management

Maintenance Therapy for Elderly Colorectal Cancer Patients with Bevacizumab: Single Center Experience

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