Effect of maximum-tolerated doses and low-dose metronomic chemotherapy on serum vascular endothelial growth factor and thrombospondin-1 levels in patients with advanced nonsmall cell lung cancer.
BACKGROUND
Angiogenesis is regulated by a balance of both angiogenic inducers and inhibitors. This study was designed to evaluate the effect of both maximum-tolerated doses (MTD) and low-dose metronomic chemotherapy (LDM) on serum vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP1) and VEGFR1 concentrations in patients with advanced nonsmall cell lung cancer.


METHODS
Forty consecutive patients with advanced stage nonsmall cell lung cancer were included in this prospective study. Twenty patients received MTD chemotherapy including 75 mg/m2 of cisplatin and 75 mg/m2 of docetaxel on day 1. The LDM treatment consisted of cisplatin 25 mg/m2 and docetaxel 25 mg/m2 were given to other 20 patients on weeks 1, 2 and 3. Serum levels were prospectively measured in serum by ELISA at four times; before chemotherapy and at 1, 2 and 3 weeks following initiation of chemotherapy.


RESULTS
The major finding in this study that MTD chemotherapy but not LDM chemotherapy resulted in significant changes in VEGFR1 and TSP1 serum levels. Due to the effect of LDM chemotherapy, we showed no statistically significant change in patients for all serum VEGF, TSP1 and VEGFR1 levels. Similarly, serum VEGF levels did not also change under MTD chemotherapy. The MTD chemotherapy induced significant and long-lasting increase of TSP1 levels and decrease of VEGFR1 levels that persisted for at least 3 weeks after the chemotherapy initiation. No significant correlations were found between serum VEGF and TSP1 levels in cancer patients treated with both LDM and MTD chemotherapy. The circulating angiogenic balance (TSP1/VEGF) is decreased in cancer patients (P=0.039).


CONCLUSIONS
The continuous/metronomic chemotherapy may not achieve a more pronounced antiangiogenic effect than MTD-scheduling chemotherapy. Future studies involving a larger number of patients are needed to confirm the present findings.
Tas
Faruk
F
Institute of Oncology, Istanbul University, Capa, 34390 Istanbul, Turkey. faruktas2002@yahoo.com
Duranyildiz
Derya
D
Soydinc
Hilal O
HO
Cicin
Irfan
I
Selam
Meltem
M
Uygun
Kazim
K
Disci
Rian
R
Yasasever
Vildan
V
Topuz
Erkan
E
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000503:physiopathology; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage; D019700:Thrombospondin 1 / Q000097:blood / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000187:drug effects; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000187:drug effects
D043823:Taxoids; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D040281:Vascular Endothelial Growth Factor Receptor-1; D002945:Cisplatin