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Monitoring platinum levels in patients receiving cisplatin or other platinum-containing drugs
Cisplatin (cis-diamminedichloroplatinum)(1) and carboplatin (cyclobutanedicarboxylatoplatinum)(2,3) are used in cancer chemotherapy. Clinical trials demonstrate schedule-dependent activity of carboplatin in patients with relapsed and refractory acute leukemia. Patients responding to carboplatin therapy had peak serum platinum concentration in the range of 0.6 to 1.8 mcg/mL. Trough concentrations ranged from 0.1 to 0.4 mcg/mL. Platinum concentrations maintained >1.8 mcg/mL can induce neutropenia and renal failure if coadministered with nephrotoxic antibiotics.(1,2)
Unexposed individuals should have platinum concentrations <0.04 mcg/mL.(4)
Cisplatin Infusion, Peak: 0.6-1.8 mcg/mL
Cisplatin Infusion, Trough: 0.1-0.4 mcg/mL
Unexposed: <0.04 mcg/mL
-Patients responding to carboplatin therapy had peak plasma platinum concentration in the range of 0.6 to 1.8 mcg/mL.
-Trough concentrations range from 0.1 to 0.4 mcg/mL.
-Platinum concentrations maintained >1.8 mcg/mL can induce neutropenia, and renal failure if coadministered with nephrotoxic antibiotics.
-Unexposed patients should have platinum concentrations <0.04 mcg/mL.
Platinum concentrations maintained >1.8 mcg/mL can induce neutropenia, and renal failure if co-administered with nephrotoxic antibiotics. The dose-limiting toxicity of carboplatin in leukemia patients was prolonged neutropenia. Other toxicities include renal failure, particularly in the setting of nephrotoxic antibiotics and amphotericin.
Interpretation requires knowledge of the time of serum collection relative to dosing. Peak platinum concentration is achieved within 30 minutes of the end of infusion, while the trough platinum concentration occurs just before the next dose.
1. Katano K, Tsujitani S, Oka S, et al: Pharmaocokinetics of hypotonic cisplatin chemotherapy administered into the peritoneal and pleural cavities in experimental model. Anticancer Res 2000;20:1603-1607
2. Kaufmann SJ, Karp JE, Letendre L, et al: Phase I and pharmacologic study of infusional topotecan and Carboplatin in relapsed and refractory acute leukemia. Clin Cancer Res 2005;11:6641-6649
3. Lindauer A, Eickhoff C, Kloft C et al: Population pharmacokinetics of high-dose carboplatin in children and adults. Ther Drug Monit 2010;32:159-168