title: Phase I study of the effects of renal impairment on the pharmacokinetics and safety of satraplatin in patients with refractory solid tumors.
abstract: BACKGROUND
  Satraplatin is an oral platinum analog with demonstrated activity in a range of malignancies. The current study was designed to evaluate the effect of varying degrees of renal impairment on the safety and pharmacokinetics (PKs) of satraplatin.
  
  
  METHODS
  Patients with advanced solid tumors, refractory to standard therapies, were eligible. The study included four cohorts of patients with varying levels of renal function, and eight patients per cohort: Group 1 (G1) = normal renal function; G2 = mild renal impairment [creatinine clearance (CrCl) 50-80 ml/min]; G3 = moderate impairment (CrCl 30 to <50 ml/min); G4 = severe impairment (CrCl <30 ml/min). Satraplatin was administered orally at 80 mg/m(2)/day on days 1-5 every 35 days.
  
  
  RESULTS
  A total of 32 patients were enrolled, 8 patients in each renal function group. Each group tolerated the dose of 80 mg/m(2)/day on days 1-5 every 35 days without the need for dose deescalation. The most common adverse events were fatigue (63%), nausea (56%), diarrhea (53%), anorexia (47%), constipation (38%), vomiting (28%), anemia, dyspnea, and thrombocytopenia (25%). There were no dose-limiting toxic effects in any study group. There was increased exposure to plasma platinum and plasma ultrafiltrate platinum in patients with moderate to severe renal impairment.
  
  
  CONCLUSIONS
  Satraplatin PKs was altered in patients with renal impairment. However, a corresponding increase in satraplatin-related toxic effects was not observed.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, Mount Sinai School of Medicine, New York 10029, USA. matthew.galsky@mssm.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Galsky
authors.forename: L H
authors.initials: LH
authors.lastname: Camacho
authors.forename: E G
authors.initials: EG
authors.lastname: Chiorean
authors.forename: D
authors.initials: D
authors.lastname: Mulkerin
authors.forename: D S
authors.initials: DS
authors.lastname: Hong
authors.forename: W K
authors.initials: WK
authors.lastname: Oh
authors.forename: D F
authors.initials: DF
authors.lastname: Bajorin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C081294:satraplatin