Translating biological insights into clinical endpoints in neuro-oncology.

摘要

On March 31,2009, the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee voted unanimously in favour of approving bevacizumab as a single agent for recurrent glioblastoma multiforme, which is among the deadliest human cancers.1 The dismal prognosis in glioblastoma outcome addresses the urgent need for the translation of new biological insights into clinical endpoints that can eventually improve patient management.2"4 On May 5, 2009, the FDA granted accelerated approval of bevacizumab for patients with glioblastoma with progressive disease following prior treatment. The new indication was granted under an FDA programme that allows for the provisional approval of medicines for cancer or other life-threatening diseases. Bevacizumab was the first clinically available angiogenesis inhibitor in the United States, and is a recombinant humanised monoclonal antibody that binds and neutralises the biological activity of human vascular endothelial growth factor (VEGF). In addition to its antiangiogenic effects, bevacizumab also reduces vascular permeability, and therefore brain oedema induced by VEGF, and stabilises the blood-brain barrier. The drug was first approved in 2004 for combination use with standard chemotherapy for metastatic colon cancer and non-small-cell lung cancer. In 2008, it was approved by the FDA for the use in metastatic breast cancer, against the recommendation of its advisory panel, who objected because the drug slowed tumour growth but did not extend survival of patients.