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

The nephrotoxic effects of different platinum compounds based combination c hemotherapies were compared. Chemotherapy consisted of either cisplatin fra ctionated over 5 days (5 x 20 mg/m(2)) or given as a single-day infusion (1 x 50 mg/m(2)) plus ifosfamide (4 g/m(2)) or high-dose chemotherapy was app lied including carboplatin (3 x 500 mg/m(2)) and ifosfamide (3 x 4 g/m(2)) fractionated over three consecutive days. Conventional parameters such as s erum creatinine and glomerular filtration rate (GFR), as well as urinary pr otein excretion of N-acetyl-beta -D-glucosaminidase (NAG)) and alpha (1)-mi cro-globulin were assessed in 52 patients. Fractionation over 5 days withou t adding other nephrotoxic agents, Le. ifosfamide, prevented decreases in G FR following cisplatin, whereas the combination of conventional dose cispla tin and Ifosfamide, given as a single-day infusion, and high-close carbopla tin/ifosfamide yielded a pronounced fall of GFR All groups showed increases in the urinary excretion levels of serum derived proteins and NAG, but wit h significant differences; about 2 to 3-fold for 5-days cisplatin, 3 to 5-f old for single-day cisplatin/ifosfamide, and 20 to 35-fold for high-dose ch emotherapy. Thus conventional approaches can reduce but not prevent the nep hrotoxicity of cisplatin-based chemotherapy. In particular, high-dose chemo therapy regimens including carboplatin and ifosfamide are associated with c omparable or even higher nephrotoxicity to single-day cisplatin/ Ifosfamide . In the light of the long-term consequences of persistent renal damage pre vention of nephrotoxicity should be further improved.