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British Journal of Cancer (2013) 109, 14081413 | doi: 10.1038/bjc.2013.409
Keywords: bevacizumab; capecitabine; imatinib; oxaliplatin; colorectal cancer; safety
Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205
T Hoehler1, G von Wichert2, C Schimanski3, S Kanzler4, M H Moehler3, A Hinke5, T Seufferlein2, J Siebler6, A Hochhaus7, D Arnold8, M Hallek9, R Hofheinz10,12 and U T Hacker*,11,12
1Department I of Internal Medicine, Prosper Hospital Recklinghausen, 44879 Recklinghausen, Germany; 2Department I of Internal Medicine, Universitaetsklinikum Ulm, 89081 Ulm, Germany; 3Department I of Internal Medicine, University of Mainz, 55099 Mainz, Germany; 4Department II of Internal Medicine, Leopoldina Krankenhaus, 97422 Schweinfurt, Germany; 5WiSP GmbH, 40764 Langenfeld, Germany; 6Department I of Internal Medicine, Universitaetsklinikum Erlangen, 91054 Erlangen, Germany;
7Department II of Internal Medicine, Hamatologie/Onkologie, Universitaetsklinikum Jena, 07740 Jena, Germany; 8Klinik fr Tumorbiologie, 79106 Freiburg, Germany; 9Department I of Internal Medicine, Center of Integrated Oncology (CIO) Cologne/ Bonn, Uniklinik Koeln, 50924 Cologne, Germany; 10Department III of Internal Medicine, Universitaetslinikum Mannheim, 68167 Mannheim, Germany and 11University Cancer Center Leipzig (UCCL), Universitaetsklinikum Leipzig, 04103 Leipzig, Germany
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 114; 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 121 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:...