Hartmann J T, Fels L M, Franzke A, Knop S, Renn M, Maess B, Panagiotou P, Lampe H, Kanz L, Stolte H, Bokemeyer C
Department of Hematology, Oncology, Immunology, UKT-Medical Center II, University of Tübingen, Germany.
Anticancer Res. 2000 Sep-Oct;20(5C):3767-73.
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.
比较了不同铂类化合物联合化疗的肾毒性作用。化疗方案包括顺铂分5天给药（5×20mg/m²）或单日输注（1×50mg/m²）加异环磷酰胺（4g/m²），或应用含卡铂（3×500mg/m²）和异环磷酰胺（3×4g/m²）的大剂量化疗，连续3天给药。对52例患者评估了血清肌酐、肾小球滤过率（GFR）等常规参数，以及N-乙酰-β-D-氨基葡萄糖苷酶（NAG）和α1-微球蛋白的尿蛋白排泄情况。顺铂分5天给药且不添加其他肾毒性药物（即异环磷酰胺）可防止顺铂治疗后GFR下降，而常规剂量顺铂与异环磷酰胺单日输注联合使用以及大剂量卡铂/异环磷酰胺则导致GFR显著下降。所有组血清来源蛋白和NAG的尿排泄水平均升高，但存在显著差异；5天顺铂组约升高2至3倍，单日顺铂/异环磷酰胺组升高3至5倍，大剂量化疗组升高20至35倍。因此，传统方法可减轻但不能预防基于顺铂的化疗的肾毒性。特别是，含卡铂和异环磷酰胺的大剂量化疗方案与单日顺铂/异环磷酰胺相比，肾毒性相当甚至更高。鉴于持续性肾损伤的长期后果，应进一步改善肾毒性的预防。
