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Cancer Chemother Pharmacol. 2016 Feb;77(2):333-8. doi: 10.1007/s00280-015-2939-9. Epub 2015 Dec 21.

A pharmacokinetic analysis of cisplatin and 5-fluorouracil in a patient with esophageal cancer on peritoneal dialysis.

Author information

1
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.
2
Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
3
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
4
Division of Nephrology and Hypertension, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA.
5
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH, USA.

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.

KEYWORDS:

5-Fluorouracil; Cisplatin; Peritoneal dialysis; Pharmacokinetics

PMID:
26687170
PMCID:
PMC5090976
DOI:
10.1007/s00280-015-2939-9
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare that they have no conflict of interest.

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