Phase I and pharmacologic study of penclomedine, a novel alkylating agent, in patients with solid tumors

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
S O'ReillyE K Rowinsky

Abstract

To determine the maximum-tolerated dose (MTD), principal toxicities, and pharmacologic behavior of penclomedine, a novel alkylating agent. Penclomedine (45 to 550 mg/ m2/d every 3 weeks) was administered as a 1- or 3-hour intravenous (IV) infusion for 5 consecutive days to patients with solid tumors. On a 1-hour dosing schedule, ataxia, vertigo, nystagmus, and a motor aphasia were the principal toxicities of penclomedine. These neurologic effects were dose-related, and evolved from complaints of somnolence and dizziness, to more pronounced signs and symptoms of cerebellar dysfunction. Up to and including doses of 415 mg/m2, these effects were well tolerated and resolved within 2 hours posttreatment. In contrast, both patients treated at the 550-mg/m2 dose level experienced a dose-limiting constellation of perinfusional aphasia and vertigo, with either ataxia of over 2 weeks' duration or recurrent dizziness. Prolongation of the infusion duration to 3 hours at this dose level resulted in less neurotoxicity; however, delayed trilineage hematologic toxicity precluded timely administration on this schedule. A statistically significant relationship was demonstrated between the development of ataxia and maximum plasma concentrations o...Continue Reading

Citations

Mar 4, 2009·Cancer Chemotherapy and Pharmacology·Lee Roy MorganBranko S Jursic
Aug 13, 2005·Cancer Chemotherapy and Pharmacology·Robert F Struck, William R Waud

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