ABSTRACT
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.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Transitional Cell/drug therapy , Daunorubicin/administration & dosage , Urologic Neoplasms/drug therapy , Aged , Antibiotics, Antineoplastic/adverse effects , Carcinoma, Transitional Cell/secondary , Chest Pain/chemically induced , Daunorubicin/adverse effects , Female , Hematologic Diseases/chemically induced , Humans , Liposomes , Male , Treatment FailureABSTRACT
Twenty-five previously untreated patients with measurable locally advanced and/or metastatic transitional cell carcinoma of the urinary bladder were included in a phase II study with carboplatin. Bolus injections were administered in 2 courses every 4 weeks at an initial dose of 400 to 450 mg/m2 with the option of increasing the dose to 450 to 500 mg/m2 in individual patients during the second cycle, depending on haematological toxicity. Two patients had a complete response (CR), 13 showed no change (NC) and 9 had progression of disease (PD), including 4 early progressions. There was no delay in treatment because of myelosuppression. Thrombocytopenia led to a reduction in drug dosage. No reduction in renal function was observed. Increased dosage did not increase the response rate. This study indicated the low effectiveness of single agent carboplatin in transitional cell carcinoma of the urinary bladder.
