title: Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients.
  
  
  METHODS
  We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma.
  
  
  RESULTS
  From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001).
  
  
  CONCLUSIONS
  This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.
authors.affiliation: 3rd Department of Medical Oncology, Theagenion Cancer Hospital, Al, Simeonidi str 2, 54007 Thessaloniki, Greece. konstantinos.papazisis@gmail.com
authors.forename: Konstantinos T
authors.initials: KT
authors.lastname: Papazisis
authors.forename: Lukas F
authors.initials: LF
authors.lastname: Kontovinis
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: George
authors.initials: G
authors.lastname: Kouvatseas
authors.forename: Christos
authors.initials: C
authors.lastname: Lafaras
authors.forename: Evangelos
authors.initials: E
authors.lastname: Antonakis
authors.forename: Maria
authors.initials: M
authors.lastname: Christopoulou
authors.forename: Charalambos
authors.initials: C
authors.lastname: Andreadis
authors.forename: Despoina
authors.initials: D
authors.lastname: Mouratidou
authors.forename: Alexandros H
authors.initials: AH
authors.lastname: Kortsaris
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000556:secondary*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007211:Indoles; D010446:Peptide Fragments; D011758:Pyrroles; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077210:Sunitinib