[Effects of combination chemotherapy with cis-diamminedichloroplatinum (II) (CDDP) on renal function in patients with urogenital malignancies]

Abstract

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.