Biological Effects After Discontinuation of VEGFR Inhibitors in Metastatic Renal Cell Cancer

To gain greater insight into the biological mechanisms occurring shortly after discontinuation of VEGFR TKIs treatment because of progressive disease (PD). Sixteen patients with PD during treatment with sorafenib or sunitinib were randomized to either directly stop the VEGFR TKI or to continue for a...

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Bibliographic Details
Published in:Anticancer research 2015-10, Vol.35 (10), p.5601-5606
Main Authors: Boers-Sonderen, Marye J, Desar, Ingrid M E, Fütterer, Jurgen J, Mulder, Sasja F, De Geus-Oei, Lioe-Fee, Mulders, Peter F, Van Der Graaf, Winette T A, Oyen, Wim J G, Van Herpen, Carla M L
Format: Article
Language:English
Subjects:
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - metabolism
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - metabolism
Carcinoma, Renal Cell - secondary
Female
Follow-Up Studies
Humans
Indoles - administration & dosage
Kidney Neoplasms - drug therapy
Kidney Neoplasms - metabolism
Kidney Neoplasms - pathology
Male
Middle Aged
Multimodal Imaging - methods
Neoplasm Staging
Niacinamide - administration & dosage
Niacinamide - analogs & derivatives
Phenylurea Compounds - administration & dosage
Prognosis
Prospective Studies
Pyrroles - administration & dosage
Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors
Withholding Treatment
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Summary:To gain greater insight into the biological mechanisms occurring shortly after discontinuation of VEGFR TKIs treatment because of progressive disease (PD). Sixteen patients with PD during treatment with sorafenib or sunitinib were randomized to either directly stop the VEGFR TKI or to continue for another two weeks. At baseline (i.e. at the moment of PD) and after two weeks FDG-PET/CT, functional-MRI and blood biomarkers of disease were evaluated. A statistically significant difference in median change from baseline to two weeks later in K(trans) and LDH levels was observed between patients who directly stopped versus those who continued treatment (1.6 s(-1) versus -1.1s(-1), p=0.03; -73.0 U/L versus 52.0 U/L, p=0.008; respectively). There were no further differences between groups. Two weeks after discontinuation of VEGFR TKIs in mRCC because of PD, a rise in K(trans) accompanied by a decrease in LDH indicates an increase in tumor vascularization. This implies that at the moment of PD the effect of VEGFR TKIs is not completely exhausted.
ISSN:1791-7530