Comparative study of the pharmacokinetics and toxicity of high-dose epirubicin with or without dexrazoxane in patients with advanced malignancy

PURPOSEWe evaluated the toxicity and pharmacokinetics of the combination of dexrazoxane with epirubicin at dexrazoxane/epirubicin dose ratios of 5 to 9:1 in a controlled, crossover phase I study in patients with advanced malignancy.PATIENTS AND METHODSThirty-eight patients with a variety of malignancies were enrolled. Assessable patients received two cycles of chemotherapy consisting of epirubicin alone and in combination with dexrazoxane. Comparisons were made between the toxicity and pharmacokinetics of epirubicin in the two treatment arms, using each patient as his or her own control. Dexrazoxane and epirubicin were delivered at dose levels of 600/120 mg/m2, 900/120 mg/m2, 900/135 mg/m2, 900/150 mg/m2, and 1,200/135 mg/m2, respectively. Twenty-six patients completed two cycles of chemotherapy and were therefore assessable.RESULTSThe maximum-tolerated doses (MTDs) of dexrazoxane/epirubicin were 1,200/135 mg/m2, with the dose-limiting toxicities being neutropenia, infection, and stomatitis. There was no ...