Phase I study of vandetanib with radiotherapy and temozolomide for newly diagnosed glioblastoma.
ABSTRACT Increasing evidence has suggested that angiogenesis inhibition might potentiate the effects of radiotherapy and chemotherapy in patients with glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition might be of therapeutic benefit, because the epidermal growth factor receptor is upregulated in GBM and contributes to radiation resistance. We conducted a Phase I study of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed GBM combined with RT and temozolomide (TMZ).
A total of 13 GBM patients were treated with vandetanib, radiotherapy, and concurrent and adjuvant TMZ, using a standard "3 + 3" dose escalation. The maximal tolerated dose was defined as the dose with <1 of 6 dose-limiting toxicities during the first 12 weeks of therapy. The eligible patients were adults with newly diagnosed GBM, Karnofsky performance status of >or=60, normal organ function, who were not taking enzyme-inducing antiepileptic drugs.
Of the 13 patients, 6 were treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed dose-limiting toxicities within the first 12 weeks, including gastrointestinal hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and diverticulitis with gastrointestinal perforation in 1 patient. The other 7 patients were treated with 100 mg daily, with no dose-limiting toxicities observed, establishing this dose as the maximal tolerated dose combined with TMZ and RT.
Vandetanib can be safely combined with RT and TMZ in GBM patients. A Phase II study in which patients are randomized to vandetanib 100 mg daily with RT and TMZ or RT and TMZ alone is underway.
Article: Anti-angiogenic therapy in glioma.[Show abstract] [Hide abstract]
ABSTRACT: There has been great interest in developing anti-angiogenic therapies for the treatment of patients with high-grade gliomas. In fact, some anti-angiogenic agents are now routinely used for the treatment of patients with glioblastoma. However, the use of these agents is largely based on trials which indicate an initial radiographic response, while it remains unclear whether any anti-angiogenic therapies tested to date have improved the overall survival of patients with malignant glial tumours. This manuscript reviews the landscape of anti-angiogenic therapy in glioma, with a focus on GBM, and demonstrates that further innovation is needed to determine the true utility of anti-angiogenic therapy.Clinical and Translational Oncology 05/2011; 13(5):294-300. · 1.28 Impact Factor
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ABSTRACT: Glioblastoma is a deadly brain disease and modest improvement in survival has been made. At initial diagnosis, treatment consists of maximum safe surgical resection, followed by temozolomide and chemoirradiation or adjuvant temozolomide alone. However, these treatments do not improve the prognosis and survival of patients. New treatment strategies are being sought according to the biology of tumors. The epidermal growth factor receptor has been considered as the hallmark in glioma tumors; thereby, some antibodies have been designed to bind to this receptor and block the downstream signaling pathways. Also, it is known that vascularization plays an important role in supplying new vessels to the tumor; therefore, new therapy has been guided to inhibit angiogenic growth factors in order to limit tumor growth. An innovative strategy in the treatment of glial tumors is the use of toxins produced by bacteria, which may be coupled to specific carrier-ligands and used for tumoral targeting. These carrier-ligands provide tumor-selective properties by the recognition of a cell-surface receptor on the tumor cells and promote their binding of the toxin-carrier complex prior to entry into the cell. Here, we reviewed some strategies to improve the management and treatment of glioblastoma and focused on the use of antibodies.Autoimmune diseases. 01/2013; 2013:716813.
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ABSTRACT: Individualized therapies are popular current concepts in oncology and first steps towards stratified medicine have now been taken in neurooncology through implementation of stratified therapeutic approaches. Knowledge about the molecular basis of brain tumors has expanded greatly in recent years and a few molecular alterations are studied routinely because of their clinical relevance. However, no single targeted agent has yet been fully approved for the treatment of glial brain tumors. In this review, we argue that multidisciplinary and integrated approaches are essential for translational research and the development of new treatments for patients with malignant gliomas, and we present a conceptual framework in which to place the components of such an interdisciplinary approach. We believe that this ambitious goal can be best realized through strong cooperation of brain tumor centers with local hospitals and physicians; such an approach enables close dialogue between expert subspecialty clinicians and local therapists to consider all aspects of this increasingly complex set of diseases.Acta Neuropathologica 05/2013; · 9.73 Impact Factor