Pharmacokinetics and toxicity of carboplatin used for hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of epithelial ovarian cancer

Mette Schou Mikkelsen*, Jan Blaakaer, Lone Kjeld Petersen, Luise Gram Schleiss, Lene Hjerrild Iversen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

17 Downloads (Pure)

Abstract

Carboplatin is frequently used in various doses for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of epithelial ovarian cancer (EOC) although its pharmacokinetics, including focus on the perfusion time, has not been evaluated when used in modern era cytoreductive surgery (CRS). The aim was to evaluate the pharmacokinetics and hematological toxicity of carboplatin used for HIPEC with a perfusion time of 90 min. Fifteen patients with stage III-IV primary EOC received CRS and 90 min of HIPEC with carboplatin at dose 800 mg/m2. For the pharmacokinetic analysis, perfusate and blood samples were obtained during HIPEC and up to 48 h after HIPEC (blood only). Hematological toxicity within 30 days was graded according to Common Terminology Criteria for Adverse Events. Severe toxicity (grades 3-5) is reported. Mean maximum concentration of carboplatin was 12 times higher in perfusate than plasma (mean CmaxPF=348 μg/mL (range: 279-595 μg/mL) versus mean CmaxPL=29 μg/mL (range: 21-39 μg/mL)). Mean terminal half-life of carboplatin in perfusate was 104 min (range: 63-190 min) and mean intraperitoneal-to-plasma area under the concentration-time curve (AUC) ratio was 12.3 (range: 7.4-17.2). Two patients (13%) had grade 3 neutropenia within 30 days. No grade 4-5 hematological toxicities were identified. Carboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m2. Large interindividual differences were found in the pharmacokinetic parameters, making risk of systemic exposure difficult to predict.

Original languageEnglish
Article number20200137
JournalPleura and Peritoneum
Volume5
Issue number4
Number of pages8
ISSN2364-7671
DOIs
Publication statusPublished - 1. Dec 2020

Keywords

  • carboplatin
  • hyperthermic intraperitoneal chemotherapy
  • ovarian epithelial cancer
  • pharmacokinetics

Fingerprint

Dive into the research topics of 'Pharmacokinetics and toxicity of carboplatin used for hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of epithelial ovarian cancer'. Together they form a unique fingerprint.

Cite this