577 Amifostine reduces cumulative cisplatin nephrotoxicity

• Published in: European journal of cancer (1990) 1995-11, Vol.31, p.S123-S123
• Main Authors: Capizzi, R.L., Scheffler, B.S., Oster, W., Habboubi, N., Schein, P.S.
• Format: Article
• Language: English
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/0959-8049(95)95831-P

Cisplatin nephrotoxicity is cumulative and generally persists after cisplatin is discontinued. Following appropriate hydration, 740–910 mg/m 2 Ami and 120 mg/m 2 cisplatin were administered to 74 patients every 28 days. Objective responses were noted in 46, 53 and 83% of patients with melanoma, head and neck and non-small cell lung cancers, respectively. ≥ 40% decrease in creatinine clearance following ≥ 4 cycles of 120 mg/m 2 cisplatin occurred in only 6% (3/49) of patients. These results are consistent with nephroprotective effects in the Ami arm of the randomized trial ofcisplatin (P) (100 mg/m 2) and cyclophosphamide (C) (1000 mg/m 2) ± Ami (910 mg/m 2) in patients with advanced ovarian cancer in which only 10% (9/88) of the Ami-treated patients vs 32% (29/91) of control patients ( P < 0.001) had ≥40% reduction in creatinine clearance after ≥ 4 cycles of CP therapy. The 32% incidence of cisplatin-induced reduction in creatinine clearance observed in the control patients ofthis randomized trial is comparable to literature reports of 35–45% incidence of ≥ 40% decrease in creatinine clearance following cumulative cisplatin doses of 400-600 mg/m 2. Thus, Ami's reduction of cumulative renal toxicity to 6–10% following repetitive doses of 100–120 mg/m 2 cisplatin represents a significant adjunct to preserve renal function. The high response rates reflect selective cytoprotection for normal tissues.