尿路性器癌に対するCis-Diamminedichloroplatinum(2) (CDDP)多剤化学療法時にみられる腎機能障害の検討

Abstract

1) CDDP投与総量360～1, 966 mg(平均868 mg)の1群(精巣腫瘍10例)では, Ccrに平均30%の減少がみられ, 尿中β2MGや(N-acetyl-β-glucosaminidase)(NAG)の排泄増加に示される尿細管障害が持続した.このCcrの減少程度とCDDP投与総量とはほぼ平行した.2)投与総量80～480 mg(平均217 mg)の2群(精巣腫瘍以外の尿路性器癌12例)では, Ccrが正常の40～50%であり, 尿細管障害も存在していることもあって, 1群におけるよりも少量で, 各パラメーターに1群と同程度の異常を来した.3) CDDPの反復投与中, 総量が600 mgをこえるころより持続的なβ2MGやNAG排泄増加がみられる様になるが, 特にNAGの測定は, CDDP投与直後から数日間の急性期の尿細管障害のチェックに有用である.腎機能不全の発現には個体差や治療開始時の腎機能レベルが関係する故, 投与中時々Ccr, β2MG, NAGをパラメーターとしてチェックするがよい

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.