Journal of Clinical Oncology, Vol 10, 1788-1794, Copyright © 1992 by American Society of Clinical Oncology
Suramin: rapid loading and weekly maintenance regimens for cancer patients
RE van Rijswijk, AC van Loenen, J Wagstaff, E Meijer, R Lopez, CJ van Groeningen, JJ Heimans and HM Pinedo
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
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 micrograms/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
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.
