CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients.
BACKGROUND
Blood-based biomarkers may be particularly useful for patient selection and prediction of treatment response for angiogenesis inhibitors. Circulating endothelial cells (CECs) and haematopoietic progenitor cells (HPCs) might have a role in tumour angiogenesis and in tumour growth. Measurement of CECs and HPCs in the blood of patients could be a simple, non-invasive way to monitor or predict responses to treatment.


METHODS
(VEGFR2(+)) CECs(,) (CD133(+)) HPCs, plasma vascular endothelial growth factor (VEGF) and erythropoietin were measured in blood from 25 non-small cell lung cancer (NSCLC) patients before and during treatment with sorafenib plus erlotinib (SO/ER). In order to assess the drug specificity of changes in CECs and HPCs, 18 patients treated with bevacizumab plus erlotinib (BV/ER) and 10 patients with erlotinib (ER) monotherapy were studied. Response was measured in all patient groups by Response Evaluation Criteria in Solid Tumors (RECIST).


RESULTS
At day 7, SO/ER-treated patients showed a three-fold increase in CECs (P<0.0001) comparable to BV/ER-treated patients (P<0.01), and the CECs did not change with erlotinib treatment (P=0.8). At day 7, CD133(+)/HPCs decreased with SO/ER treatment (P<0.0001). HPC numbers did not change with either BV/ER or erlotinib. In SO/ER-treated patients pre-treatment CD133(+)/HPCs were significantly lower in responders (P=0.01) and pre-treatment CD133(+)/HPC numbers lower than the median correlated with a longer time-to-progression (TTP) (P=0.037).


CONCLUSIONS
Pre-treatment CD133(+)/HPCs are a promising candidate biomarker to further explore for use in selecting NSCLC patients who might benefit from SO/ER treatment.
Vroling
L
L
Department of Medical Oncology, VU University Medical Center Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands.
Lind
J S W
JS
de Haas
R R
RR
Verheul
H M W
HM
van Hinsbergh
V W M
VW
Broxterman
H J
HJ
Smit
E F
EF
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010455:Peptides / Q000097:blood*; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D000077157:Sorafenib
D000071916:AC133 Antigen; D015703:Antigens, CD; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D010671:Phenylurea Compounds; D011725:Pyridines; D011799:Quinazolines; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride