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


CONCLUSIONS
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.
Department of Oncology, The Finsen Centre, Copenhagen University Hospital Rigshospitalet, Denmark. kristoffer@onkolog.dk
Kristoffer S
KS
Rohrberg
René K
RK
Olesen
Per
P
Pfeiffer
Morten
M
Ladekarl
Helle
H
Pappot
Ib J
IJ
Christensen
Gunilla
G
Høyer-Hansen
Morten
M
Sørensen
Birgit G
BG
Skov
Ian
I
Buysschaert
Peter
P
Carmeliet
Ulrik
U
Lassen
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004359:Drug Therapy, Combination / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors