Pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy for peritoneal metastasis

Gan To Kagaku Ryoho. 2014 Nov;41(12):2496-9.

Abstract

The purpose of this manuscript is to report the pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy (HIPEC) after peritonectomy.

Materials and methods: Eleven patients with peritoneal metastasis (PM) underwent peritonectomies combined with 40 min of HIPEC with 40 mg/body of docetaxel. The pharmacokinetics of docetaxel were studied by using high-performance liquid chromatography.

Results: The docetaxel concentration at the start of HIPEC (0 min) was 9.084 ± 0.972 mg/L. The concentration gradually decreased to 5.599 ± 0.458 mg/L 40 min after HIPEC. In contrast, serum docetaxel levels increased during HIPEC, reaching a maximum level of 0.1334 ± 0.0726 mg/L at 40 min. The clearance (CLp) was 3.164 ± 1.383 L/hr, and the area under the curve (AUC) ratio was 95.12 ± 87.32. The AUC ratio of less-extensive peritonectomies was significantly higher than that of extended peritonectomies. The docetaxel concentration in the tumor tissue increased at 40 min (4.45 mg/gr). The apparent permeability (Papp, 40 min) was 1.47 ± 0.67 mm/40 min. No severe adverse effects were observed after HIPEC.

Conclusion: From these results, 40 mg is a safe dose for docetaxel combined with HIPEC, and the locoregional intensity of docetaxel is enough to control PM less than 1.47 mm in diameter.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacokinetics*
  • Combined Modality Therapy
  • Docetaxel
  • Female
  • Humans
  • Hyperthermia, Induced
  • Male
  • Middle Aged
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy*
  • Taxoids / pharmacokinetics*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Taxoids
  • Docetaxel