Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature-a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye's posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.

2018-06-03·Expert Opinion on Biological Therapy3区 · 医学

Issues and promises of bevacizumab in prostate cancer treatment

3区 · 医学

Review

作者: Formica, Vincenzo ; Roselli, Mario ; Cereda, Vittore

INTRODUCTIONThere is general agreement that increased angiogenesis is an important factor in determining prostate cancer development and prognosis. Vascular Endothelial Growth Factor (VEGF) is thought to play a primary role in the molecular events that lead to prostate cancer progression, from androgen-dependency to castration-resistance until dissemination to the skeleton. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has exhibited clinical activity in different cancer types. Areas covered: In this review we summarize the data of clinical trials, investigating the effects of bevacizumab in prostate cancer patients. Until now, the drug has demonstrated anti-tumoral activity although with no improvements in overall survival (OS) and a wide range of alarming side effects in metastatic castration-resistant prostate cancer (mCRPC). Recently, promising results were achieved, using bevacizumab in combination with androgen deprivation therapy (ADT) in patients with recurrent prostate cancer after definitive local therapy. Expert opinion: The suboptimal efficacy of bevacizumab may relate to molecular events triggered during disease progression, such as redundancy of angiogenic factors or the interfering influence of androgens on angiogenic pathways. Further studies, using bevacizumab in combination with ADT and/or inhibitors of other key pathways on the subset of patients with low burden, hormone sensitive prostate cancer, need to be conducted.

2017-01-01·Journal of Cancer3区 · 医学

Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment

3区 · 医学

ArticleOA

作者: Desenclos, Christine ; Darmon, Ilan ; Blanchard, Nicolas ; Trudel, Stéphanie ; Taillandier, Luc ; Blonski, Marie ; Morisse, Mony Chenda ; Boone, Mathieu ; Coutte, Alexandre ; Roufai, Diana Bello ; Faivre, Jean-Christophe ; Le Rhun, Emilie ; Chauffert, Bruno

Background. New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy. Methods. We retrospectively analyzed tumor and target volumes and clinical neurological status in 39 patients with bulky GB and/or with severe neurological impairment after an induction treatment combining TMZ and BEV. Neurological and radiological responses were assessed according to RANO criteria. Calculating gross tumor and clinical target volumes (GTV and CTV) was done at diagnosis and before radiotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan Meier methods. Safety was reported according to NCTCAE. Results. A cohort of 39 patients was analyzed between December 2010 and April 2014. Upfront standard TMZ-based chemoradiotherapy was recused due either to tumor volume or impairment of neurological status and/or performance status. After TMZ/BEV induction (median time of 3 months), 6 (15%) patients achieved a partial response (PR), and 17 (44%) had a stable disease. 24 patients (62%) received a radical-intent chemoradiotherapy. TMZ-BEV induced median reduction of the clinical target volume (CTV) was 25.9% [-84.4%; - 4.8%]. The median PFS and OS were 8.4 months [95% CI: (6.6 - 9.9)] and 11.0 months [95% CI: (9.3 - 13.7)], respectively in the whole cohort and 10.8 [95% CI: (9.3 - 12.9)] and 15.0 [95% CI: (13.2 - 17.8)] for irradiated patients. Induction treatment led to corticosteroid dose reduction or cessation in 21 patients (54%). KPS improvement was observed in 38% of patients. Toxicity was mild with only 7/39 (18%) grade III-IV toxicity, including 1 digestive bleeding and 1 epistaxis. Conclusion. TMZ-BEV induction led to CTV reduction allowing for optimal chemoradiotherapy in a majority (62%) of patients for which radiotherapy was initially recused. A clinical benefit was obtained with improved KPS and a decrease in steroid dose.

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