Phase I clinical and pharmacokinetic study of bisantrene in refractory pediatric solid tumors

Invest New Drugs. 1986;4(2):149-53. doi: 10.1007/BF00194594.

Abstract

Fourteen patients with pediatric malignant solid tumors, median age 15 years, received 22 courses of bisantrene in a Phase I study. Dosage escalations ranged from 10 to 120 mg/m2 daily for 5 consecutive days. Toxicity included myelosuppression and phlebitis. A sensitive (detection limit of 2 ng/ml) and specific HPLC method was developed to quantitate bisantrene in patient's plasma and urine. Peak plasma concentrations at the end of 60 minute infusions ranged from 568 ng/ml at 10 mg/m2 to 6800 ng/ml at the 100 mg/m2 dosage. The elimination half life (T 1/2 beta) averaged about 10 hours but increased to 20 hours in a patient with liver disease. Only 2.4 - 10% of the bisantrene dose was eliminated in the urine suggesting that the liver may be the major route of elimination for this antineoplastic anthracene derivative.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anthracenes / adverse effects
  • Anthracenes / metabolism
  • Anthracenes / therapeutic use
  • Child
  • Child, Preschool
  • Drug Evaluation
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Neoplasms / drug therapy*

Substances

  • Anthracenes
  • bisantrene