Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205

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.