Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts.

A number of pre-clinical studies have suggested that blocking vascular endothelial growth factor (VEGF) signalling can be beneficial in combination with radiotherapy. This study investigated the effects of cediranib, a highly potent orally available inhibitor of VEGF receptor tyrosine kinase activity in combination with radiation in Calu-6 lung xenografts. In nude mice, Calu-6 tumours were established and treatments initiated at a volume of 250 mm3. Tumour-localized radiotherapy was given as three or five daily fractions of 2 Gy. Cediranib (3 mg kg−1) was administered 2 h prior to each fraction and continued post radiotherapy (concomitant regimen) or was initiated immediately after the completion of radiotherapy (sequential regimen). The endpoint was the time taken for tumour volume to quadruple (RTV4). Combined treatments resulted in a significantly enhanced growth delay compared with either modality alone. The therapeutic benefit was the same irrespective of the scheduling regimen. Tumour regression was...