Suramin: Rapid loading and weekly maintenance regimens for cancer patients

R. E N Van Rijswijk, A. C. Van Loenen, J. Wagstaff, E. Meijer, R. Lopez, C. J. Van Groeningen, J. J. Heimans, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Suramin is an anticancer agent with a narrow therapeutic window and a terminal half-life of 45 to 55 days. These characteristics make it necessary to control accurately the serum concentrations of the drug. Therefore, the aim of the present study was to develop a rapid loading regimen, followed by weekly administration of suramin to maintain serum concentrations of between 150 and 300 μg/mL for 8 weeks. Patients and Methods: Eligible patients were treated with five different loading regimens. Initially, weekly maintenance doses were estimated manually by the treating physician. Subsequently, computer-assisted dosing that used Bayesian pharmacokinetic modeling was used. Results: Thirty-eight courses of suramin that were administered to 35 patients were studied. The optimal loading regimen consisted of a continuous infusion of 600 mg/m2 during a 24-hour period, which resulted in a mean serum concentration of 319 μg/mL. Potentially toxic concentrations that were observed with shorter infusions were avoided. Maintenance treatment, which used the weekly administration of suramin during a 6-hour period, seemed to be able to maintain mean suramin serum trough concentrations of 150 μg/mL, while preventing mean peak concentrations of more than 300 μg/mL. The use of Bayesian pharmacokinetics was superior to manual estimation in tailoring the optimal dose to the therapeutic window. Conclusions: Continuous infusion is the optimal way of delivering suramin during the loading phase. To maintain trough levels and peak levels within a narrower therapeutic window, suramin will have to be administered more frequently than once a week. Bayesian modeling based on individual serum levels and population pharmacokinetics allows accurate dosing to maintain suramin levels within the therapeutic window.

Original languageEnglish (US)
Pages (from-to)1788-1794
Number of pages7
JournalJournal of Clinical Oncology
Volume10
Issue number11
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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