Clinical development of ormaplatin has been delayed because of neuroto
xicity that was not predictable on the basis of patient characteristic
s, total cumulative dose, or plasma pharmacokinetics. We report a deta
iled comparison of the plasma biotransformations of ormaplatin in two
patients at the 123 mg/m(2)dose administered as a 1-h infusion every 4
weeks. One of these patients developed neurotoxicity after 2 cycles (
total cumulative dose = 246 mg/kg), while the other patient showed no
symptoms of neurotoxicity through 2 cycles. The maximum plasma concent
ration and area under the curve for ultrafilterable platinum were grea
ter for the patient that did not develop neurotoxicity. However, both
maximum plasma concentration and area under the curve were greater for
dichloro(d,I-trans)1,2-diaminocyclohexane the major active biotransfo
rmation product of ormaplatin, in the patient that developed neurotoxi
city. In addition, analysis of plasma biotransformation products sugge
sted that the initial plasma concentrations of ormaplatin were also gr
eater in the patient that developed neurotoxicity. These data suggest
that analysis of individual plasma biotransformation products may be u
seful in predicting toxicity of platinum anticancer agents and should
be included in future phase I studies.