NEPHROTOXICITY OF HIGH-DOSE IFOSFAMIDE CARBOPLATIN/ETOPOSIDE IN ADULTS UNDERGOING AUTOLOGOUS STEM-CELL TRANSPLANTATION/

The objective of this study was to evaluate nephrotoxicity in adult pa tients treated with high-dose ifosfamide, carboplatin, and etoposide f ollowed by autologous stem cell transplantation. We conducted a retros pective analysis of clinical and laboratory data from 131 patients wit h various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem ce ll transplantation as part of a phase I/II therapeutic trial. Abnormal ities in glomerular filtration were evaluated by measuring peak creati nine levels and tubular dysfunction by the lowest recorded serum level s of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and af ter autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were >1.5 mg/dL but <3.0 mg/dL in 37% and levels were >3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3. 0 mg/dL in 25% of patients and were >3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those recei ving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potas sium, and magnesium levels immediately after chemotherapy, and they re mained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between <0.008 and <0. 001). This is the largest adult population study documenting the incid ence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.