A phase II study of DaunoXome in advanced urothelial transitional cell carcinoma.

Liposomal encapsulation of anthracyclines is claimed to reduce toxicity and to improve pharmacokinetics. Therefore, 15 patients with locally advanced or metastatic transitional cell cancer (TCC) of the urinary tract were entered into a phase II study assessing the response rate (WHO criteria) and toxicity of DaunoXome 100 mg/m2 given as a 1 h infusion every third week. During treatment, 6 patients remained stable and 8 had progressive disease. 1 patient died of pulmonary embolism after the first cycle and was not evaluable for response. No patient developed grade 4 myelotoxicity. Grade 3 leucopenia was seen in 5 patients and grade 1 thrombocytopenia in 1 patient, with no treatment-related changes of biochemical liver and kidney function tests. 4 patients complained of angina pectoris-like chest pain during the initial phase of the first or second infusion. The event was associated with a decrease in systolic blood pressure by 20-30 mm in 1 patient leading to permanent treatment discontinuation. In the other 3 and all subsequent patients, intramuscular application of 100 mg hydrocortisone 1 h prior to DaunoXome infusion prevented similar hypotensive reactions. In this study, intravenous (i.v.) DaunoXome 100 mg/m2 every third week showed no anticancer activity in advanced TCC.