Carboplatin-based chemotherapy with pharmacokinetic analysis for patients with hemodialysis-dependent renal insufficiency |
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Authors: | Robert J Motzer Donna Niedzwiecki Marion Isaacs Celia Menendez-Botet William P Tong Carlos Flombaum Howard I Scher George J Bosl |
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Institution: | (1) Genitourinary Oncology Service, Division of Solid Tumor Oncology, Cornell University Medical College, 10021 New York, New York, USA;(2) Nephrology Service Department of Medicine, Cornell University Medical College, 10021 New York, New York, USA;(3) Department of Clinical Chemistry, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, 10021 New York, New York, USA;(4) Department of Medicine, Cornell University Medical College, 10021 New York, New York, USA;(5) Memorial Hospital, 1275 York Avenue, 10021 New York, NY, USA |
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Abstract: | Summary Three patients with renal insufficiency requiring hemodialysis were treated with carboplatin at 100 mg/m2 in combination with etoposide for advanced germ-cell tumor (GCT, two cases) or Adriamycin + vinblastine for a transitional-cell carcinoma of the ureter (one case). Hemodialysis was performed 24 h after the administration of carboplatin. Both patients with GCT achieved a complete response, and the patient with transitional-cell carcinoma of the ureter was inevaluable for response but his disease has not progressed. The dose of carboplatin was increased in one patient as renal function improved on therapy. In two patients, the pharmacokinetics of carboplatin were determined; the pre-dialysis half-lives, AUC, and total body clearances of free carboplatin-derived platinum were estimated to be 32 and 18.3 h, 4.93 and 6.17 mg ml–1 min, and 18.2 and 18.7 ml/min, respectively. The dialysis elimination half-lives (t1/2 ) of 2 and 3 h, respectively, for these two patients were markedly lower than the predialysis values, indicating that carboplatin was dialyzed. In summary, carboplatin can be given to patients with severe renal insufficiency. Adequate AUCs were achieved and dialysis limited systemic exposure to free carboplatin.Robert J. Motzer, M. D., is a recipient of an American Cancer Society Career Development Award |
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