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

Anticancer Drugs. 1994 Oct;5(5):520-6. doi: 10.1097/00001813-199410000-00002.

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 level showed a Cpmax of 163 ng/ml and a t1/2 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Blood Cell Count / drug effects
  • Bone Marrow Diseases / chemically induced
  • Bone Marrow Diseases / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / pathology
  • Spectrophotometry, Atomic
  • Vomiting / chemically induced

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • ormaplatin