Hoehler, T., von Wichert, G., Schimanski, C., Kanzler, S., Moehler, M. H., Hinke, A., Seufferlein, T., Siebler, J., Hochhaus, A., Arnold, D., Hallek, M., Hofheinz, R. and Hacker, U. T. (2013). Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205. Br. J. Cancer, 109 (6). S. 1408 - 1414. LONDON: NATURE PUBLISHING GROUP. ISSN 1532-1827

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Abstract

Background: Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer. Methods: Two dose levels (I/II) were defined: capecitabine 850/1000 mg m(-2) twice daily on days 1-14; oxaliplatin 100/130 mg m(-2) on day 1; bevacizumab 7.5 mg kg(-1) on day 1; imatinib 300 mg day(-1) on days 1-21 every 21 days. The primary study endpoint was safety. The phase II secondary endpoint was 6-month progression-free survival (PFS). Results: Dose level I was chosen for phase II testing because, even though further dose escalation was permitted by the protocol, gastrointestinal toxicities were considered to be clinically significant. A total of 49 patients were evaluated. The 6-month PFS rate was 76%, median PFS was 10.6 months and median overall survival was 23.2 months. Haematological toxicities were generally mild. Sensory neuropathy and diarrhoea were the most common grade 3 toxicities. Conclusion: The combination of XELOX with bevacizumab and imatinib is tolerable and has promising efficacy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hoehler, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Wichert, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schimanski, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kanzler, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moehler, M. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hinke, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seufferlein, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siebler, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hochhaus, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofheinz, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hacker, U. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-475838
DOI: 10.1038/bjc.2013.409
Journal or Publication Title: Br. J. Cancer
Volume: 109
Number: 6
Page Range: S. 1408 - 1414
Date: 2013
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1532-1827
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PULMONARY ARTERIAL-HYPERTENSION; TUMOR VASCULATURE; 1ST-LINE THERAPY; I TRIAL; FLUOROURACIL; LEUCOVORIN; CHEMOTHERAPY; PDGF; RECEPTORS; SUNITINIBMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47583

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