Phase II trial of erlotinib and bevacizumab in patients with advanced upper gastrointestinal cancers

Department of Oncology, The Finsen Centre, Copenhagen University Hospital Rigshospitalet, Denmark.
Acta oncologica (Stockholm, Sweden) (Impact Factor: 3). 02/2012; 51(2):234-42. DOI: 10.3109/0284186X.2011.619568
Source: PubMed


Patients with upper gastrointestinal cancers have a poor prognosis and only few treatment options. The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are valid targets in many solid tumours, and they have synergistic effects in preclinical studies.
In this multi-center phase II trial patients with chemoresistant, metastatic upper gastrointestinal cancer were treated with erlotinib (150 mg daily) and bevacizumab (10 mg/kg every two weeks). Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity and biomarker correlates. Plasma samples were analysed for EGFR and angiogenesis related markers using quantitative immunoassays.
One hundred and two patients were enrolled in the trial between June 2006 and October 2007. The most common toxicities were skin reaction, diarrhoea, and fatigue. ORR was 6%, median PFS was 2.2 months, and OS 4.3 months. Low concentration of urokinase plasminogen activator receptor (uPAR) domain I was correlated to longer PFS and OS.
The combination of erlotinib and bevacizumab is well tolerated, however, with low clinical activity in patients with chemoresistant UGI cancer. Some patients do benefit from the therapy, and uPAR forms are potential biomarkers in these patients.

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Available from: Morten Ladekarl, Aug 04, 2014
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    • "Dickler et al. also showed that the combination of B + E had very limited activity in treating unselected patients with metastatic breast cancer [24]. Similarly, the combination has minimal clinical activity in patients with advanced upper gastrointestinal cancers [25] and recurrent advanced squamous cell carcinoma of the head and neck [26]. All the aforementioned studies consistently demonstrated that although B + E was a fairly well tolerated regime, it had minimal clinical activity in various solid malignancies. "
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