title: Biological Effects After Discontinuation of VEGFR Inhibitors in Metastatic Renal Cell Cancer.
abstract: OBJECTIVE
  To gain greater insight into the biological mechanisms occurring shortly after discontinuation of VEGFR TKIs treatment because of progressive disease (PD).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands marye.boers-sonderen@radboudumc.nl.
authors.forename: Marye J
authors.initials: MJ
authors.lastname: Boers-Sonderen
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Ingrid M E
authors.initials: IM
authors.lastname: Desar
authors.affiliation: Department of Radiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Jurgen J
authors.initials: JJ
authors.lastname: Fütterer
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Sasja F
authors.initials: SF
authors.lastname: Mulder
authors.affiliation: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Lioe-Fee
authors.initials: LF
authors.lastname: De Geus-Oei
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Mulders
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Winette T A
authors.initials: WT
authors.lastname: Van Der Graaf
authors.affiliation: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Carla M L
authors.initials: CM
authors.lastname: Van Herpen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D000077157:Sorafenib; D000077210:Sunitinib; D028761:Withholding Treatment
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib
keywords: Vascular endothelial growth factor receptor inhibitor; progressive disease; re-vascularization; renal cell carcinoma; treatment beyond progression; tyrosine kinase inhibitor