Probenecid and Diethyldithiocarbamate as Modifiers of Cisplatin Toxicity
Cisplatin (CP) has proved to be the most important new chemotherapeutic agent in the last two decades. The clinical use of CP in treating cancer was initially severely limited by nephrotoxicity. With the use of hydration and mannitol diuresis, renal damage was minimized for CP used at standard doses (up to 100 mg/m2). Now long-term use of the drug in responding patients is limited by renal dysfunction in approximately 20% of patients. In attempting to expand the use of cisplatin with high doses, clinicians have found nephrotoxicity, as well as other toxicities, to be dose-limiting. At Stanford University, we have conducted trials to ameliorate toxicity through two different mechanisms of action: inhibition of platinum renal secretion in the kidney by probenecid and chelation of platinum with diethyldithiocarbamate (DDTC).
KeywordsHuman Kidney Inulin Clearance Renal Handling Fractional Clearance Free Platinum
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