Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin.

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Abstract
Untrafilterable plasma and urinary levels of platinum were quantitated for 24 hours after the first- and fourth-course infusion of cisplatin (CDDP) to seven patients. Four patients received 80 mg/m2 and three patients received 100 mg/m2 CDDP as a 2-hour infusion. The area under the curve (AUC) of ultrafilterable platinum, average renal clearance (ClR) of ultrafilterable platinum and percentage of the platinum dose excreted in urine (% E) were determined for each infusion over the 26-hour period of the study. The AUC was higher in all patients after the fourth-course infusion, with a median increase of 74%. The median CLR was 494 mL/min (range 214 to 996 mL/min) for the first course and decreased 156 mL/min (range, 108 to 271 mL/min) for the fourth-course infusion (P < .02). The median %E was 29.2% (range, 19.6% to 37.7%) for the first course and decreased to 19.9% (range, 12.4% to 25.9%) for the fourth-course infusion (P < .02). There was no difference in creatinine clearance for the two infusions (median, 94 mL/min; P > .05). Urinary excretion of B2-microglobulin (B2-MG) and N-acetyl-B-glucosaminidase (NAG) was highly variable between patients and did not provide a useful predictor of changes in renal function. Four courses of CDDP therapy resulted in significantly reduced renal elimination of platinum in patients, probably through a reduction in the secretion of the drug in the proximal tubule of the kidney. The results suggest that increased antitumor effect and toxicity could occur in patients receiving sequential courses of cisplatin.