Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation

• DOI: 10.1073/pnas.1318022110
• Publication Date: 2013-11-05T01:58:48Z
• Authors: Tracy T. Batchelor; Elizabeth R. Gers...; Kyrre E. Emblem; Dan G. Duda; Jayashree Kalpath...; Matija Snuderl; Marek Ancukiewicz; Pavlina Polaskova; Marco C. Pinho; Dominique Jennings; Scott R. Plotkin; Andrew S. Chi; April F. Eichler; Jorg Dietrich; Fred H. Hochberg; Christine Lu-Emerson; A. John Iafrate; S. Percy Ivy; Bruce R. Rosen; Jay S. Loeffler; Patrick Y. Wen; A. Greg Sorensen; Rakesh K. Jain
• Keywords: 610; Angiogenesis Inhibitors; Enzyme-Linked Immunosorbent Assay; Polymerase Chain Reaction; Statistics, Nonparametric; 03 medical and health sciences; 0302 clinical medicine; 616; Biomarkers, Tumor; Temozolomide; Humans; Prospective Studies; DNA Modification Methylases; Protein Kinase Inhibitors; Research Subject Categories::MEDICINE::Surgery::Oncology; Brain Neoplasms; Tumor Suppressor Proteins; Receptor Protein-Tyrosine Kinases; Magnetic Resonance Imaging; 3. Good health; Dacarbazine; Oxygen; DNA Repair Enzymes; Treatment Outcome; Quinazolines; Glioblastoma

Antiangiogenic therapy has shown clear activity and improved survival benefit for certain tumor types. However, an incomplete understanding of the mechanisms action antiangiogenic agents hindered optimization broader application this new therapeutic modality. In particular, impact on blood flow oxygenation status (i.e., role vessel pruning versus normalization) remains controversial. This controversy become critical as multiple phase III trials anti-VEGF combined with cytotoxics failed to show overall in newly diagnosed glioblastoma (nGBM) patients several other cancers. Here, we shed light nGBM response cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, using MRI techniques biomarkers prospective II clinical cediranib chemoradiation vs. alone patients. We demonstrate that perfusion occurs only subset cediranib-containing regimens, is associated these Moreover, increase well pharmacodynamic biomarkers, such changes plasma placenta growth factor sVEGFR2. Finally, treatment resistance was elevated IL-8 sVEGFR1 posttherapy. conclusion, after may distinguish responders nonresponders early course expensive potentially toxic form therapy, results provide insight into selection most likely from treatments.