Antineoplastic activity of continuous exposure to dexrazoxane: potential new role as a novel topoisomerase II inhibitor

Semin Oncol. 1998 Aug;25(4 Suppl 10):93-9.


Although originally developed as an antitumor agent in the 1970s, dexrazoxane (DEX) is currently used as a cardioprotective agent in combination with doxorubicin (DOX). Due to concerns about anthracycline-induced cardiotoxicity at higher cumulative doses, many investigators have chosen to administer DOX by prolonged infusion. Therefore, with the ultimate goal of combining infusional DEX and DOX, we performed a phase I study of intravenous DEX alone as a 96-hour infusion. Surprisingly, the maximum tolerated dose of DEX identified in this study was 10- to 15-fold lower than previously determined using different schedules of administration. Results of pharmacokinetic studies in support of the trial have found that steady-state DEX plasma concentrations in the range of 4 to 5 micromol/L can be achieved safely. Because previous experiments have explored the ability of DEX to inhibit the catalytic activity topoisomerase II at low micromolar concentrations and due to a lack of in vitro cytotoxicity data for long-term exposures, we performed further laboratory studies to provide a context for our pharmacokinetic findings. As a result of these correlative studies, we have found that prolonged exposures to DEX are cytotoxic to human leukemic cells at concentrations that are clinically achievable.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / pharmacokinetics
  • Cardiovascular Agents / pharmacology*
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Heart Diseases / chemically induced
  • Heart Diseases / prevention & control
  • Humans
  • Razoxane / administration & dosage
  • Razoxane / pharmacokinetics
  • Razoxane / pharmacology*
  • Topoisomerase II Inhibitors*


  • Antineoplastic Agents
  • Cardiovascular Agents
  • Topoisomerase II Inhibitors
  • Razoxane
  • Doxorubicin