TY - JOUR
T1 - Phase II trial of erlotinib and bevacizumab in patients with advanced upper gastrointestinal cancers
AU - Rohrberg, Kristoffer S
AU - Olesen, René K
AU - Pfeiffer, Per
AU - Ladekarl, Morten
AU - Pappot, Helle
AU - Christensen, Ib J
AU - Høyer-Hansen, Gunilla
AU - Sørensen, Morten
AU - Skov, Birgit G
AU - Buysschaert, Ian
AU - Carmeliet, Peter
AU - Lassen, Ulrik
PY - 2012/2
Y1 - 2012/2
N2 - Background. 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. Methods. 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. Results. 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. Discussion. 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.
AB - Background. 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. Methods. 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. Results. 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. Discussion. 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.
KW - Adult
KW - Aged
KW - Angiogenesis Inhibitors
KW - Antibodies, Monoclonal, Humanized
KW - Carcinoma
KW - Disease-Free Survival
KW - Dose-Response Relationship, Drug
KW - Drug Resistance, Neoplasm
KW - Drug Therapy, Combination
KW - Female
KW - Follow-Up Studies
KW - Gastrointestinal Neoplasms
KW - Humans
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Quinazolines
KW - Receptor, Epidermal Growth Factor
KW - Survival Analysis
KW - Treatment Outcome
U2 - 10.3109/0284186X.2011.619568
DO - 10.3109/0284186X.2011.619568
M3 - Journal article
C2 - 22017239
SN - 0001-6357
VL - 51
SP - 234
EP - 242
JO - Acta Odontologica Scandinavica
JF - Acta Odontologica Scandinavica
IS - 2
ER -
