Carboplatin (CBDCA), iproplatin (CHIP), and high dose cisplatin in hypertonic saline evaluated for tubular nephrotoxicity

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Abstract
We compared the acute tubular nephrotoxicity of three platinum compounds in children and adults with solid tumors by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl-β-D-glucosaminidase, and total protein. Cisplatin (100 mg/m2) was administered with mannitol, or at a twofold larger total dosage (50 mg/m2 per day for 4 days) in a 3% saline infusion. Carboplatin (300 mg/m2) was administered in combination with 5-fluorouracil, and iproplatin was administered in dosages ranging from 216 to 388 mg/m2. Enzymuria and proteinuria induced by cisplatin at a total dosage of 200 mg/m2 on a divided schedule did not significantly differ from that observed for the single 100 mg/m2 dose. Enzymuria and proteinuria induced by carboplatin and iproplatin were significantly less than that for cisplatin; however, one patient developed chronic tubular damage after three courses of carboplatin, and the acute tubular toxicity of iproplatin in one of 15 patients was exceptional. Our findings support the value of administering cisplatin in hypertonic saline on a divided schedule as a strategy to reduce acute tubular damage. Although carboplatin and iproplatin are less nephrotoxic than cisplatin, occasionally patients experience subclinical acute or chronic tubular damage that may lead to overt nephrotoxicity with continued therapy.