title: A pharmacokinetic analysis of cisplatin and 5-fluorouracil in a patient with esophageal cancer on peritoneal dialysis.
abstract: BACKGROUND
  Very little is known about the pharmacokinetics of chemotherapeutic agents in patients also being treated with continuous ambulatory peritoneal dialysis. We sought to evaluate the pharmacokinetics of cisplatin and 5-fluorouracil in plasma and peritoneal dialysate in a patient being treated for esophageal adenocarcinoma.
  
  
  METHODS
  A single patient with esophageal adenocarcinoma and on peritoneal dialysis for end-stage renal disease was treated with cisplatin 25 mg/m(2) on day 1 of weeks 1 and 5 and continuous infusional 5-fluorouracil 1000 mg/m(2)/day on days 1-4 of weeks 1 and 5 along with daily radiation therapy. Intense plasma and dialysate sampling was performed during the week 5 administration, followed by quantitation of platinum by atomic absorption spectrophotometry and 5-fluorouracil by LC-MS/MS.
  
  
  RESULTS
  Following systemic administration, clearance of ultrafilterable (active) platinum over the first 6 h was 20.8 L/h, which is lower than previously reported clearance levels of ultrafilterable platinum. Total platinum AUC was 131 μg h/mL, also higher than an AUC previously reported for total platinum in patients with normal renal function. Platinum-related material was detected in the peritoneal cavity, but this is likely inactive. 5-Fluorouracil penetrated the intraperitoneal cavity, but the contribution of peritoneal dialysis to drug clearance was negligible at 0.072 %.
  
  
  CONCLUSIONS
  Administration of intravenous cisplatin and 5-fluorouracil chemotherapy to a patient treated with continuous ambulatory peritoneal dialysis is feasible, but clearance in dialysate is nominal, thus suggesting that dose reduction is indicated for cisplatin. Systemic drug administration results in limited intraperitoneal penetration of 5-fluorouracil and inactive platinum species.
authors.affiliation: University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH, USA. jennifer.eads@uhhospitals.org.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Eads
authors.affiliation: Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.|Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
authors.affiliation: Division of Nephrology and Hypertension, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Negrea
authors.affiliation: Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Julianne L
authors.initials: JL
authors.lastname: Holleran
authors.affiliation: Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Strychor
authors.affiliation: University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH, USA.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000473:pathology / Q000628:therapy; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D015314:Dialysis Solutions / Q000032:analysis; D004938:Esophageal Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D010530:Peritoneal Dialysis / Q000379:methods*; D013053:Spectrophotometry / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D015314:Dialysis Solutions; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-Fluorouracil; Cisplatin; Peritoneal dialysis; Pharmacokinetics