title: A prospective evaluation of VEGF-targeted treatment cessation in metastatic clear cell renal cancer.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF)-targeted therapy is administered continuously until progression in metastatic clear cell renal cancer (mRCC). The role of intermittent therapy is under investigation. Preclinical data raise concerns about this approach.
  
  
  METHODS
  This study combined the data from three similar phase II studies investigating VEGF-targeted therapy prior to planned nephrectomy for untreated mRCC (European Union Drug Regulating Authorities Clinical Trials 2006-004511-21, 2006-006491-38 and 2009-016675-29). The significance of progression during the planned treatment break (median 4.3 weeks) was assessed.
  
  
  RESULTS
  Sixty-two patients had a structured treatment interruption for nephrectomy after achieving clinical benefit from treatment and restarted therapy. Twenty-three of these patients (37%) progressed (Response Evaluation Criteria In Solid Tumors v1.1) on the first scan after the treatment break. Subsequent stabilisation of disease occurred in 16 of the 23 (70%) progressing patients when the same VEGF tyrosine kinase inhibitor (TKI) was reintroduced. Baseline characteristics, such as the Memorial Sloan Kettering Cancer Centre prognostic score, did not predispose to the development of this progression. Progression during the treatment break was associated with an increased risk of death on multivariate analysis {hazard ratio (HR) 5.56; [95% confidence interval 2.29-13.5], P < 0.01}. Sequential fluorodeoxyglucose positron emission tomography showed a rebound in metabolic activity during the treatment break.
  
  
  CONCLUSIONS
  Progression during planned VEGF TKI treatment interruptions is frequent and associated with a poor prognosis. Treatment cessation should be pursued with caution.
authors.affiliation: Experimental Cancer Centre, Barts Cancer Institute, Queen Mary, University of London, St Bartholomew's Hospital, London, UK. thomas.powles@bartshealth.nhs.uk
authors.forename: T
authors.initials: T
authors.lastname: Powles
authors.forename: I
authors.initials: I
authors.lastname: Kayani
authors.forename: K
authors.initials: K
authors.lastname: Sharpe
authors.forename: L
authors.initials: L
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.forename: G D
authors.initials: GD
authors.lastname: Stewart
authors.forename: D
authors.initials: D
authors.lastname: Berney
authors.forename: A
authors.initials: A
authors.lastname: Sahdev
authors.forename: S
authors.initials: S
authors.lastname: Chowdhury
authors.forename: E
authors.initials: E
authors.lastname: Boleti
authors.forename: J
authors.initials: J
authors.lastname: Shamash
authors.forename: A R
authors.initials: AR
authors.lastname: Reynolds
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Blank
authors.forename: J
authors.initials: J
authors.lastname: Haanen
authors.forename: A
authors.initials: A
authors.lastname: Bex
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009392:Nephrectomy / Q000379:methods; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D019275:Radiopharmaceuticals; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000187:drug effects; D028761:Withholding Treatment
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D019275:Radiopharmaceuticals; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; C516667:pazopanib; D000077210:Sunitinib
keywords: FDG-PET; VEGF-targeted therapy; intermittent treatment; metastatic renal cancer; nephrectomy