title: Suramin: rapid loading and weekly maintenance regimens for cancer patients.
abstract: OBJECTIVE
  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 micrograms/mL for 8 weeks.
  
  
  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 micrograms/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 micrograms/mL, while preventing mean peak concentrations of more than 300 micrograms/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.
authors.affiliation: Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: R E
authors.initials: RE
authors.lastname: van Rijswijk
authors.forename: A C
authors.initials: AC
authors.lastname: van Loenen
authors.forename: J
authors.initials: J
authors.lastname: Wagstaff
authors.forename: E
authors.initials: E
authors.lastname: Meijer
authors.forename: R
authors.initials: R
authors.lastname: Lopez
authors.forename: C J
authors.initials: CJ
authors.lastname: van Groeningen
authors.forename: J J
authors.initials: JJ
authors.lastname: Heimans
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D001499:Bayes Theorem; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D013498:Suramin / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D013498:Suramin