Year: 2013
Type: article
Abstract: The last several years have witnessed burgeoning interest in targeting the VEGF pathway in glioblastomas. Given the dramatic responses seen with targeting the ligand (bevacizumab), attempts to target VEGFR have naturally followed. Cediranib is an orally available pan-VEGF tyrosine kinase inhibitor. A carefully documented small phase II study at a daily dose of 45 mg in recurrent glioblastomas demonstrated a partial response rate of 27% and PFS-6 of 26%, meeting its primary endpoint. Moreover, serial MR spectroscopy studies suggested a possible direct effect of the drug on tumor metabolism. Notably, almost half the patients required dose reduction because of toxicity. These results spawned a phase III trial in glioblastoma patients at first recurrence. Anti-VEGF therapy-naïve patients with tumor progression despite radiation and temozolomide were randomized to cediranib alone (30 mg), CCNU + cediranib (20 mg, based on pilot data demonstrating synergistic myelosuppression), or CCNU alone in a 2:2:1 ratio. The primary endpoint was blinded, independent assessment of PFS in each cediranib group compared to the lomustine group, with secondary endpoints including radiographic response, overall survival, PFS-6, and time to neurologic deterioration.
Source: Neuro-Oncology
Authors: K. Aldape, W. Pope, J. Huse, D. Schiff, G. Zadeh
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4246555920