title: Sunitinib and sorafenib in metastatic renal cell carcinoma patients with renal insufficiency.
abstract: BACKGROUND
  Although clinical trials with sunitinib and sorafenib in metastatic renal cell carcinoma (mRCC) have included patients with moderate renal insufficiency (RI), the incidence of renal toxicity induced by their administration as well as the safety of these agents in patients with more severe renal insufficiency has not been extensively reported.
  
  
  METHODS
  Patients with mRCC treated with vascular endothelial growth factor-targeted therapy with either RI at time of treatment initiation or who developed RI during therapy were identified. RI was defined as serum creatinine (Cr) > or = 1.9 mg/dl or a creatinine clearance (CrCl) < 60 ml/min/1.73 m(2) for >3 months before treatment. Objective outcomes and toxic effects of treatment were also measured.
  
  
  RESULTS
  A total of 39 patients were identified: 21 patients who initiated therapy with preexisting RI and 18 patients who developed RI during treatment. In patients with RI at the start of therapy, Cr increased in 57%, and 48% of patients required dose reduction. The median time to maximum RI was 6.6 months (range 0.4-19.6 months). In patients who developed RI while receiving therapy, median serum Cr and CrCl at the start of therapy were 1.5 mg/dl (range 1.1-1.8) and 61 ml/min (range 43-105), respectively. Patients experienced a median increase in serum Cr of 0.8 mg/dl (range 0.3-2.8) and a median decrease in CrCl of 25 ml/min (range 8.54-64.76). Overall, 5 patients (24%) achieved a partial response (PR), 13 (62%) had stable disease (SD) and 3 (14%) had progressive disease (PD). Estimated progression-free survival (PFS) was 8.4 months. The most common toxic effects (all grades) were fatigue (81%), hand-foot syndrome (HFS) (52%) and diarrhea (48%). Six patients experienced grade III toxicity (29%), primarily HFS.
  
  
  CONCLUSIONS
  Sunitinib and sorafenib can be safely given to patients with renal insufficiency, provided adequate monitoring of renal function. For those patients developing an increase in Cr, dose modifications may be required to allow continuation of therapy. The clinical outcome of patients with baseline renal dysfunction and patients who develop renal dysfunction does not appear to be compromised.
authors.affiliation: Department of Internal Medicine, Medicine Institute.
authors.forename: G
authors.initials: G
authors.lastname: Khan
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Golshayan
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wood
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Garcia
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bukowski
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: rinib2@ccf.org.
authors.forename: B
authors.initials: B
authors.lastname: Rini
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000150:complications*; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib