Circulating endothelial cells and endothelial progenitors as predictive markers of clinical response to bevacizumab-based first-line treatment in advanced colorectal cancer patients.
BACKGROUND
Despite the consistent clinical results demonstrated by studies on anti-angiogenic drugs targeted against the vascular endothelial growth factor in metastatic colorectal cancer (mCRC) patients, no specific direct/indirect biomarker of their efficacy has been validated. In this field, circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs) have recently been proposed as noninvasive biomarkers.


METHODS
The absolute numbers of CEPs, total CECs (tCECs) and their resting (rCECs) and activated subsets were evaluated by multiparameter flow cytometry in 40 mCRC patients at baseline and before the administration of the third and sixth course of a bevacizumab-based first-line treatment. Fifty healthy subjects were utilized as control.


RESULTS
The overall response rate was 80%, overall clinical benefit was 90% and median progression-free survival (PFS) was 13.8 months. In our patients, tCECs and rCECs were significantly increased compared with healthy subjects. The patients who achieved a radiological response showed, at baseline, a significant decrease of rCECs and a trend in decrease of tCECs in comparison with patients not achieving response. Finally, a baseline absolute number of tCEC and rCEC <40 cells/ml was evidenced in patients with a longer PFS. No correlation was found regarding CEP.


CONCLUSIONS
Our study suggests significant correlations between both tCEC and rCEC baseline levels and the antitumor efficacy of a bevacizumab-based combination therapy in mCRC patients, thus confirming that these biomarkers could be used in the clinical setting as an early predictor of tumor response.
Ronzoni
M
M
Medical Oncology, Scientific Institute S. Raffaele, Milano. Electronic address: ronzoni.monica@hsr.it.
Manzoni
M
M
Medical Oncology.
Mariucci
S
S
Medical Oncology.
Loupakis
F
F
Medical Oncology 2, Department of Oncology, University Hospital of Pisa, Pisa, Italy.
Brugnatelli
S
S
Medical Oncology.
Bencardino
K
K
Medical Oncology, Scientific Institute S. Raffaele, Milano.
Rovati
B
B
Medical Oncology.
Tinelli
C
C
Biometry and Clinical Epidemiology Unit, Foundation IRCCS Policlinico S. Matteo, Pavia.
Falcone
A
A
Medical Oncology 2, Department of Oncology, University Hospital of Pisa, Pisa, Italy.
Villa
E
E
Medical Oncology, Scientific Institute S. Raffaele, Milano.
Danova
M
M
Medical Oncology.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D054316:Biomarkers, Pharmacological / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000473:pathology*; D011379:Prognosis; D013234:Stem Cells / Q000473:pathology / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D000068258:Bevacizumab