Phase I and pharmacokinetic study of intraperitoneal thioTEPA in patients with ovarian cancer

Cancer Chemother Pharmacol. 1990;26(4):283-7. doi: 10.1007/BF02897231.

Abstract

A total of 15 patients with residual ovarian cancer confined to the peritoneal cavity after first-line systemic chemotherapy were treated with triethylene-thiophosphoramide (thioTEPA) in a phase I study. A total of 50 courses of thioTEPA were given intraperitoneally in doses ranging from 30 to 80 mg/m2. The dose limiting toxicity was myelosuppression, which occurred at 80 mg/m2 and was frequently prolonged. Short-lived nausea and vomiting was easily controlled, and there was no local toxicity. Three patients remain free of disease progression at 6, 6 and 12 months. ThioTEPA concentrations were measured by gas chromatography. Peritoneal fluid concentrations declined rapidly in a first-order fashion, with a half-life of 0.96 +/- 0.1 h. A mean of 93% of the drug was absorbed during the 4-h dwell time. Peak plasma levels were achieved 30-60 min after drug instillation and were substantially lower than corresponding peritoneal levels. A pharmacokinetic advantage for intraperitoneal delivery was detected for peak drug concentration (24.9 +/- 8.5) and AUC (9.2 +/- 4.8). Based on this study, the recommended dose for intraperitoneal thioTEPA is 60 mg/m2 every 3-4 weeks. However, the rapid absorption of this drug from the peritoneum, secondary to thioTEPA's small molecular weight and lipophilic nature, suggests that it has only a limited role in intraperitoneal therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ascites / prevention & control
  • Ascitic Fluid / metabolism
  • Catheters, Indwelling
  • Drug Evaluation
  • Female
  • Half-Life
  • Humans
  • Injections, Intraperitoneal
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Palliative Care
  • Thiotepa / adverse effects
  • Thiotepa / pharmacokinetics
  • Thiotepa / therapeutic use*

Substances

  • Thiotepa