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01.04.2013 | Original Article

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

verfasst von: Jane Kendrew, Rajesh Odedra, Armelle Logié, Paula J. Taylor, Sharon Pearsall, Donald J. Ogilvie, Stephen R. Wedge, Juliane M. Jürgensmeier

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2013

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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

Combining cediranib with selected cytotoxic or targeted agents proved efficacious in a range of human tumour xenograft models.

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Titel: Anti-tumour and anti-vascular effects of cediranib (AZD2171) alone and in combination with other anti-tumour therapies
verfasst von: Jane Kendrew
Rajesh Odedra
Armelle Logié
Paula J. Taylor
Sharon Pearsall
Donald J. Ogilvie
Stephen R. Wedge
Juliane M. Jürgensmeier
Publikationsdatum: 01.04.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2097-x

Springer Medizin

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