Phase I clinical and pharmacokinetic study of zeniplatin, a new platinum complex.

Abstract

Forty-six patients with refractory solid malignancies received the new platinum complex [2,2-bis(aminomethyl)-1,3-propanediol-N-N'] [1,1-cyclobutanedicarboxylato] [(2-)0,0')] platinum (zeniplatin). Zeniplatin was given, without hydration or mannitol, as a 60- to 90-min i.v. infusion every 3 weeks at doses ranging from 8 to 145 mg/m2. The maximum tolerated dose of zeniplatin was 145 mg/m2. The dose-limiting toxicity of zeniplatin was dose-related leukopenia and neutropenia, with the nadir usually observed between 1 and 2 weeks after therapy and recovery usually occurring by 3 weeks after therapy. Thrombocytopenia was rare. The most prominent non-hematological side-effect of zeniplatin was nausea and vomiting. Other non-hematological side-effects were mild or absent. Zeniplatin did not induce significant neurological or auditory toxicity. Zeniplatin was not nephrotoxic at doses less than or equal to 120 mg/m2. At 145 mg/m2, the clearance decreased by a mean of 40% after 2 cycles of therapy. Two patients, one with malignant melanoma and one with renal cell cancer, achieved a partial response. Pharmacokinetics of free (plasma ultrafiltrates) and total platinum in plasma were determined in 5 patients. An in vitro study of the rate and extent of zeniplatin binding to protein in human plasma was also performed. Free and total platinum were measured by flameless atomic absorption spectrometry; free zeniplatin was measured in ultrafiltrate by HPLC. Total and free plasma platinum concentrations were co-modelled using the information from the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: P F Dodion, D de Valeriola, N Crespeigne, J D Kantrowitz, M Piccart, F Wery, J Kerger, M J Egorin, A Forrest, N R Bachur
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 2 Issue 8 Pg. 589-96 (Sep 1991) ISSN: 0923-7534 [Print] England
• PMID: 1793726 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• zeniplatin
• Carboplatin

Topics

• Adult
• Aged
• Antineoplastic Agents (pharmacology)
• Carboplatin (analogs & derivatives, pharmacokinetics, therapeutic use)
• Colorectal Neoplasms (drug therapy)
• Female
• Follow-Up Studies
• Head and Neck Neoplasms (drug therapy)
• Humans
• Infusions, Intravenous
• Kidney (pathology)
• Leukopenia (chemically induced)
• Male
• Melanoma (drug therapy)
• Metabolic Clearance Rate
• Middle Aged
• Neoplasms (drug therapy)
• Neutropenia (chemically induced)
• Thrombocytopenia