Phase I and pharmacokinetic study of LU79553, a DNA intercalating bisnaphthalimide, in patients with solid malignancies (original) (raw)

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2001

Abstract

To determine the maximum-tolerated dose and characterize the pharmacokinetic behavior of LU79553, a novel bisnaphthalimide antineoplastic agent, when administered as a daily intravenous infusion for 5 days every 3 weeks. Patients with advanced solid malignancies received escalating doses of LU79553. Plasma sampling and urine collections were performed on both days 1 and 5 of the first course. Thirty patients received 105 courses of LU79553 at doses ranging from 2 to 24 mg/m(2)/d. Proximal myopathy, erectile dysfunction, and myelosuppression precluded the administration of multiple courses at doses above 18 mg/m(2)/d. These toxicities were intolerable in two of six patients after receiving three courses at the 24-mg/m(2)/d dose level. At the 18-mg/m(2)/d dose, one of six patients developed febrile neutropenia and grade 2 proximal myopathy after three courses of LU79553. The results of electrophysiologic, histopathologic, and ultrastructural studies supported a drug-induced primary my...

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