PHASE-I CLINICAL-TRIAL OF ORMAPLATIN (TETRAPLATIN, NSC-363812)

Ormaplatin is a platinum analog that was developed because of an alter ed toxicity profile and non-cross resistance to cisplatin in both in v itro and in vivo models. To determine the toxicities and maximum toler ated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days a t nine dose levels ranging from 1.0 to 15.0 mg/m(2)/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelo suppression were moderate and not dose-limiting. Dose-limiting neuroto xicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m(2). This neurotoxicity was symptomatic in all patients and ca used significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy a nalysis performed for one patient at the 13.0 mg/m(2)/day dose level s howed a Cp(max) of 163 ng/ml and a t(1/2) of 10.9 min for free platinu m. A phase II dose could not be determined due to the onset of periphe ral neuropathy at low cumulative doses and not at absolute dose levels .