Comparative study of the acute nephrotoxicity from standard dose cisplatin +/- ifosfamide and high-dose chemotherapy with carboplatin and ifosfamide

Abstract

The nephrotoxic effects of different platinum compounds based combination chemotherapies were compared. Chemotherapy consisted of either cisplatin fractionated over 5 days (5 x 20 mg/m2) or given as a single-day infusion (1 x 50 mg/m2) plus ifosfamide (4 g/m2) or high-dose chemotherapy was applied including carboplatin (3 x 500 mg/m2) and ifosfamide (3 x 4 g/m2) fractionated over three consecutive days. Conventional parameters such as serum creatinine and glomerular filtration rate (GFR), as well as urinary protein excretion of N-acetyl-beta-D-glucosaminidase (NAG)) and alpha 1-micro-globulin were assessed in 52 patients. Fractionation over 5 days without adding other nephrotoxic agents, i.e. ifosfamide, prevented decreases in GFR following cisplatin, whereas the combination of conventional dose cisplatin and ifosfamide, given as a single-day infusion, and high-dose carboplatin/ifosfamide yielded a pronounced fall of GFR. All groups showed increases in the urinary excretion levels of serum derived proteins and NAG, but with significant differences; about 2 to 3-fold for 5-days cisplatin, 3 to 5-fold for single-day cisplatin/ifosfamide, and 20 to 35-fold for high-dose chemotherapy. Thus, conventional approaches can reduce but not prevent the nephrotoxicity of cisplatin-based chemotherapy. In particular, high-dose chemotherapy regimens including carboplatin and ifosfamide are associated with comparable or even higher nephrotoxicity to single-day cisplatin/ifosfamide. In the light of the long-term consequences of persistent renal damage prevention of nephrotoxicity should be further improved.