[Amifostine as protective agent in cisplatin-based chemotherapy of advanced bladder cancer]

Abstract

Amifostine is an organic thiophsophate which protects normal cells from the effects of chemotherapy with reduced nadir and duration of cyclophosphamide induced neutropenia, reduced cisplatin derived renal and neurological complications being described. However, no data are available for urological malignancies treated with cisplatin-based chemotherapy. Aim of the study was to assess the efficacy of pretreatment with amifostine in terms of prevention of renal, hematopoietic and neurologic toxicity. 17 patients (mean age: 62.6 [45-74]) with advanced transitional cell carcinoma of the urinary bladder received inductive or adjuvant cisplatin based chemotherapy (1-6 cycles) with a cisplatin dose of 70 mg/m(2). Amifostine (740-910 mg/m(2)) was administered intravenously 30 minutes prior to chemotherapy. For all patients creatinine clearance, serum creatinine and electrolytes including magnesium, and blood cell count were determined prior to and after each cycle. A group of 12 patients (mean age: 61.9 [51-67]) did undergo MVEC chemotherapy (1-4 cycles) without receiving amifostine and served as control group. Amifostine was well tolerated and only 1 patient suffered from gastrointestinal discomfort, blood pressure remained unchanged in all patients. Amifostine prevented a significant reduction of creatinine clearance even in the 2 patients with known renal insufficiency: mean creatinine clearance was 125 +/- 20 ml/min prior to and 115 +/- 25 ml/min after chemotherapy. In the control group, however, creatinine clearance dropped from 121 +/- 30 ml/min to 85 +/- 20 ml/min after completion of MVEC chemotherapy. Serum creatinine levels did not increase significantly (1.1 mg/dl prior to and 1.2 mg/dl after chemotherapy), magnesium levels did not decrease significantly and normalized at the end of chemotherapy. Significant neutropenia and thrombocytopenia developed in 29 % and 12 % of the patients in the amifostine group and in 67 % and 33 % of the patients in the control group. Amifostine was shown to have a protective effect against cisplatin induced nephrotoxicity in the elderly patient undergoing systemic chemotherapy. Based on our data amifostine should be applied in the supportive management to prevent chemotherapy induced complications.