Phase I clinical trial of ormaplatin (tetraplatin, NSC 363812)

T. J. O'Rourke, G. R. Weiss, P. New, H. A. Burris, G. Rodriguez, J. Eckhardt, J. Hardy, J. G. Kuhn, S. Fields, G. M. Clark, D. D. Von Hoff

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m2/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m2. This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m2/day dose leve showed a Cp(max) of 163 ng/ml and a t( 1/2 ) of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.

Original languageEnglish (US)
Pages (from-to)520-526
Number of pages7
JournalAnti-Cancer Drugs
Volume5
Issue number5
DOIs
StatePublished - 1994

Keywords

  • neurotoxicity
  • ormaplatin
  • phase I trial

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

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