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Anti-tumour and anti-vascular effects of cediranib (AZD2171) alone and in combination with other anti-tumour therapies

Lookup NU author(s): Professor Steve WedgeORCiD

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Abstract

Cediranib (AZD2171) is a highly potent inhibitor of all three vascular endothelial growth factor receptors. The aim of this preclinical study was to examine the effect of combining cediranib with mechanistically distinct anti-tumour therapies.Cediranib (1.5 or 3 mg/kg/day) was evaluated alone and in combination with either gefitinib, imatinib, ZD6126, saracatinib, selumetinib, bevacizumab, 5-fluorouracil (5-FU), docetaxel, oxaliplatin, gemcitabine, pemetrexed, irinotecan or cisplatin in human tumour xenograft models. Anti-tumour activity was measured by assessing the change in tumour volume following treatment compared with vehicle-treated time-matched controls.In all cases, the combination regimens, at tolerated doses and schedules, inhibited tumour growth to a greater extent than the corresponding monotherapy treatments. Compared with cediranib alone, statistically significant enhancements in anti-tumour activity were observed with all combination regimens. Notably, after 14 days of treatment, the combination of cediranib with ZD6126 induced substantial tumour regression (60 % compared with pre-treatment volume), whilst treatment with each agent alone led only to partial growth inhibition. A combination of cediranib with gefitinib also induced tumour regressions, and cediranib combined with either gemcitabine or irinotecan was found to inhibit tumour growth profoundly (by 99 and 98 %, respectively).Combining cediranib with selected cytotoxic or targeted agents proved efficacious in a range of human tumour xenograft models.

Publication metadata

Author(s): Kendrew J, Odedra R, Logie A, Taylor PJ, Pearsall S, Ogilvie DJ, Wedge SR, Jurgensmeier JM

Publication type: Article

Publication status: Published

Journal: Cancer Chemotherapy and Pharmacology

Year: 2013

Volume: 71

Issue: 4

Pages: 1021-1032

Print publication date: 01/04/2013

Online publication date: 26/01/2013

Acceptance date: 14/01/2013

ISSN (print): 0344-5704

ISSN (electronic): 1432-0843

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00280-013-2097-x

DOI: 10.1007/s00280-013-2097-x

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