577 Amifostine reduces cumulative cisplatin nephrotoxicity

Abstract

Cisplatin nephrotoxicity is cumulative and generally persists after cisplatin is discontinued. Following appropriate hydration, 740–910 mg/m2 Ami and 120 mg/m2 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/m2 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/m2) and cyclophosphamide (C) (1000 mg/m2) ± Ami (910 mg/m2) 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/m2. Thus, Ami's reduction of cumulative renal toxicity to 6–10% following repetitive doses of 100–120 mg/m2 cisplatin represents a significant adjunct to preserve renal function. The high response rates reflect selective cytoprotection for normal tissues. Cisplatin nephrotoxicity is cumulative and generally persists after cisplatin is discontinued. Following appropriate hydration, 740–910 mg/m2 Ami and 120 mg/m2 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/m2 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/m2) and cyclophosphamide (C) (1000 mg/m2) ± Ami (910 mg/m2) 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/m2. Thus, Ami's reduction of cumulative renal toxicity to 6–10% following repetitive doses of 100–120 mg/m2 cisplatin represents a significant adjunct to preserve renal function. The high response rates reflect selective cytoprotection for normal tissues.