HIGH-DOSE CISPLATIN THERAPY USING MANNITOL VERSUS FUROSEMIDE DIURESIS - COMPARATIVE PHARMACOKINETICS AND TOXICITY

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 65  (1-2) , 73-78
Abstract
The dose-limiting toxic effect of high-dose (100 mg/m2) cisplatin is renal insufficiency. Hydration with furosemide- or mannitol-induced diuresis has been reported to ameliorate this toxicity. Animal studies suggest that mannitol may be superior to furosemide in this regard. Twenty-two patients with advanced neoplasms refractory to conventional therapy were treated with cisplatin at a dose of 100 mg/m2 every 21-28 days. Patients were randomized to receive 37.5 g of mannitol by 6 h infusion with cisplatin or 40 mg of furosemide prior to cisplatin therapy. Hydration with at least 1 l of normal saline was given prior to cisplatin. Nephrotoxicity (creatinine > 2 mg/100 ml, creatinine clearance < 50 ml/min) occurred in 19% of courses in the furosemide-treated group and in 28% of courses in the mannitol-treated group. Peak plasma Pt concentration, terminal half-life, urinary excretion and percent protein-bound plasma Pt were similar in both groups. The use of cisplatin at this dose schedule resulted in similar toxicity and pharmacokinetics when using hydration with furosemide or mannitol.