Journal of Clinical Oncology, Vol 4, 1392-1398, Copyright © 1986 by American Society of Clinical Oncology
Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin
PA Reece, I Stafford, J Russell and PG Gill
Ultrafilterable 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 (CIR) 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 to 156 mL/min (range, 108 to 271 mL/min)
for the fourth- course infusion (P less than .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 less than .02). There was
no difference in creatinine clearance for the two infusions (median, 94
mL/min; P greater than .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.
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