Kawamura J, Hida S, Higashi Y, Yamauchi T, Soeda A, Yoshida O
Hinyokika Kiyo. 1985 Feb;31(2):207-21.
The renal function in 23 patients with advanced urogenital cancers (10 testicular, 8 uroepithelial, 3 prostatic cancers and 1 penile cancer) treated with a total of 3 or 4 cycles of combination chemotherapy including CDDP was examined prospectively, by measuring of creatinine clearance (Ccr), fractional excretion of beta 2 microglobulin (FE beta 2 MG) and urinary N-acetyl-beta-glucosaminidase (NAG). Patients with testicular cancers (group 1) who received the cumulative CDDP dose of 360-1966 mg (on average 868 mg), the decrease in Ccr and increase in FE beta 2 MG and NAG were temporary during each chemotherapy cycle. However, in the overall course, after the cumulative dose exceeded 600 mg, higher beta 2 MG excretion persisted and after the cumulative dose exceeded 800 mg, Ccr decreased to 30% of the pretreatment level. This suggests cumulative delayed, irreversible renal damage. The severity of decrease in Ccr paralleled the increase in cumulative CDDP dose. Patients with urogenital cancers other than testicular cancer (group 2) who received the cumulative CDDP dose of 80-480 mg (on average 217 mg), and who had decreased Ccr and tubular damage prior to treatment, even though the cumulative dose was lower than in group 1, changes in Ccr, FE beta 2 MG and NAG were almost in the same magnitude as in group 1. Determination of NAG is useful for detection of the early change in the tubules several days after CDDP administration, while that of beta 2 MG is useful for detection of the chronic damage of renal tubules after several cycles of CDDP chemotherapy. CDDP nephrotoxicity is characterized by dose-dependent tubular damage. Although renal injury may not be evident during the early course of treatment, repeated courses of CDDP may lead to clinically serious chronic renal failure.
对23例晚期泌尿生殖系统癌症患者(10例睾丸癌、8例尿路上皮癌、3例前列腺癌和1例阴茎癌)进行了前瞻性研究,这些患者接受了总共3或4个周期的含顺铂联合化疗,通过测量肌酐清除率(Ccr)、β2微球蛋白排泄分数(FEβ2MG)和尿N-乙酰-β-葡萄糖苷酶(NAG)来检测肾功能。睾丸癌患者(第1组)接受的顺铂累积剂量为360 - 1966mg(平均868mg),在每个化疗周期中,Ccr降低以及FEβ2MG和NAG升高是暂时的。然而,在整个疗程中,累积剂量超过600mg后,β2MG排泄持续升高,累积剂量超过800mg后,Ccr降至预处理水平的30%。这提示存在累积性延迟性、不可逆的肾损伤。Ccr降低的严重程度与顺铂累积剂量的增加平行。除睾丸癌外的泌尿生殖系统癌症患者(第2组)接受的顺铂累积剂量为80 - 480mg(平均217mg),且在治疗前Ccr降低和肾小管损伤,尽管累积剂量低于第1组,但Ccr、FEβ2MG和NAG的变化幅度与第1组几乎相同。NAG的测定有助于在顺铂给药几天后检测肾小管的早期变化,而β2MG的测定有助于在顺铂化疗几个周期后检测肾小管的慢性损伤。顺铂肾毒性的特征是剂量依赖性肾小管损伤。虽然在治疗早期肾损伤可能不明显,但重复使用顺铂疗程可能导致临床上严重的慢性肾衰竭。