Chemotherapy with cisplatin, epirubicin and docetaxel in transitional cellurothelial cancer. Phase II trial

Cisplatin (CDDP), epirubicin (EPI) and docetaxel have single agent activity against urothelial transitional cell carcinoma (TCC). We evaluated the eff icacy and toxicity of this combination in locally advanced or metastatic ur othelial TCC. Patients with urothelial TCC who had no prior chemotherapy (p rior adjuvant chemotherapy >6 months allowed) were eligible for entry the s tudy. Eligibility criteria were performance status 0-3, granulocyte count ( AGC) greater than or equal to 1.5 (10(9)/l), platelet count greater than or equal to 100 (10(9)/l), clearance creatine greater than or equal to 60 ml/ min and total bilirubin level less than or equal to 1.5 mg/dl. Treatment co nsisted of EPI 40 mg/m(2) intravenous push, docetaxel 75 mg/m(2) in 1 h inf usion with premedication and CDDP 75 mg/m(2) with pre- and posthydration. T reatment was repeated every 21 days. Antiemetics with dexamethasone and 5-H T3 antagonists were used routinely. Prophylactic haematopoietic growth fact ors were not used. Patients were evaluated for toxicity weekly and assessed for response every two cycles of treatment. 32 patients were entered into the study and 30 patients (7 with locally advanced and 23 with metastatic d isease) were assessable for response. There were 9 (30.0%) complete respons es (2, 28.6% in locally advanced and 7, 30.4% in metastatic disease) and 11 (36.7%) partial responses (3, 42.9% in locally advanced and 8, 34.8% b in metastatic disease) with an overall response rate (RR) of 66.7% (71.5% in l ocally advanced, 65.2% in metastatic disease). Overall median survival was 14.5 months (15 months for locally advanced, 12.5 months for metastatic dis ease). The median duration of response in patients with metastatic disease was 8.5 months. 16 (53.3%) patients required one dose reduction and 5 (16.7 %) patients required two dose reductions for a nadir AGC less than or equal to 500/mm(3). Four episodes of febrile neutropenia and sepsis occurred. No patient had a dose reduction or treatment delay for any other grade 3/4 to xicity. There were no treatment delays due to myelotoxicity. Alopecia was u niversal. Non-haematological toxicity including mucositis, fluid retention, allergy, cutaneous toxicity, diarrhoea and neurotoxicity were mild and inf requent. The combination of EPI, docetaxel and CDDP is an active regimen fo r urothelial TCC. The response rate and toxicity were comparable with the M -VAC (methotrexate, vinblastine, doxorubicin, cisplastin) regimen, Phase II I trials comparing this regimen with M-VAC are warranted. (C) 2000 Elsevier Science Ltd, All rights reserved.