title: Treatment-related deterioration of renal function is associated with the antitumor efficacy of sunitinib in patients with metastatic renal cell carcinoma.
abstract: Some "on-target" adverse events, such as hypertension and thrombocytopenia, have been reported to predict the antitumor efficacy of sunitinib as first-line therapy in patients with metastatic renal cell carcinoma (mRCC). However, it is unclear whether the degree of deterioration of renal function resulting from inhibition of the vascular endothelial growth factor signaling pathway can predict the antitumor efficacy of sunitinib. Therefore, the aim of the present study was to investigate whether the degree of deterioration of renal function can predict the antitumor efficacy of sunitinib in patients with mRCC.
  
  
  
  The present study retrospectively reviewed the medical records of patients with histologically confirmed mRCC who were treated with sunitinib for>3 months between March 2008 and September 2014. The degree of deterioration of the estimated glomerular filtration rate (eGFR) and the progression-free survival (PFS) and overall survival (OS) were compared.
  
  
  
  The study included 62 patients with mRCC. The 62 study patients were divided into the following 2 subgroups according to whether they had a≥10% decrease in the eGFR during sunitinib therapy: Group 1 (≥10% decrease in the eGFR, N = 47 [76%]) and Group 2 (<10% decrease in the eGFR, N = 15 [24%]). PFS was significantly longer in Group 1 than in Group 2 (16mo vs. 6mo, P = 0.001). In multivariate analysis, the Memorial Sloan-Kettering Cancer Center risk group (favorable vs. intermediate, hazard ratio [HR] = 3.7; favorable vs. poor, HR = 14.7, P = 0.05), number of sunitinib courses (HR = 0.64, P<0.0001), baseline eGFR (HR = 0.96, P = 0.0057), and a≥10% decrease in the eGFR (HR = 3.2, P = 0.017) were identified as independent predictors of PFS. In addition, the OS was significantly longer in Group 1 than in Group 2 (not reached vs. 13mo, P = 0.034). In multivariate analysis, a≥10% decrease in the eGFR (HR = 0.98, P = 0.97) was not identified as an independent predictor of OS.
  
  
  
  The degree of deterioration of renal function might predict the antitumor efficacy of sunitinib in patients with mRCC.
authors.affiliation: Department of Urology, Tokyo Women׳s Medical University, Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Fukuda
authors.affiliation: Department of Urology, Tokyo Women׳s Medical University, Tokyo, Japan. Electronic address: tkondo@kc.twmu.ac.jp.
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Urology, Toda Chuo General Hospital, Saitama, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Iida
authors.affiliation: Department of Urology, Tokyo Women׳s Medical University, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Department of Urology, Tokyo Women׳s Medical University, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D015398:Signal Transduction; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib
keywords: Antitumor efficacy; Renal cell carcinoma; Renal dysfunction; Sunitinib