POSSIBLE CORRELATION BETWEEN ORMAPLATIN BIOTRANSFORMATIONS AND NEUROTOXICITY

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.