Long term renal toxicity of ifosfamide in adult patients – 5 year data
Introduction
Ifosfamide is indicated as first line treatment in a variety of solid tumours in adults. It is known to be nephrotoxic and is often used following therapy with, or as concomitant therapy with other potent nephrotoxins, including cisplatin, antimicrobial, antifungal and antiviral medications. To date, there are sparse case reports on the incidence of acute kidney injury (AKI) or chronic kidney disease (CKD) in adults exposed to ifosfamide. The available data on the long term renal complications for patients exposed to ifosfamide are thus based entirely on the paediatric population. Risk factors for nephrotoxicity that have been identified in this population include high cumulative doses (>60 g/m2); younger age1; concomitant treatment with cisplatin, and prior unilateral nephrectomy.2 Chloroacetaldehyde, a metabolite of ifosfamide, is toxic to epithelial cells and may contribute to nephrotoxicity of the parent drug.3, 4 Histopathological changes include both glomerular and tubular injuries.5
The aim of this study was to assess the long term effects of ifosfamide exposure on renal function in an adult population and to determine if there are any treatment or patient specific factors that contribute to long term nephrotoxicity. This represents the only long term study on the nephrotoxicity of ifosfamide in adults.
Section snippets
Methods
Retrospective chart analysis was performed with the approval of the Institutional Review Board of Memorial Sloan Kettering Cancer Center. Protected health information was coded in accordance with the requirements of Health Insurance Portability and Accountability Act. We reviewed the database to identify all patients 16 years or older who received ifosfamide between 11th January 2000 and 19th January 2004. If ifosfamide treatment was initiated prior to 11th January 2000 at Memorial Sloan
Results
Table 1, Table 2 present data on patient characteristics and classes of chemotherapies used in combination with ifosfamide, respectively. The mean age at the start of treatment was 43.5 years (range 16.2–77 years). Most patients (49%) were treated for non-Hodgkins lymphoma, and equal percentages were treated for Hodgkins lymphoma and sarcoma (25%). A few patients had more than one malignancy. Five patients (2%) had a prior nephrectomy and 24 (9%) patients received pelvic irradiation. Hypotension
Discussion
To date, published data on the short and long term renal complications of ifosfamide exposure have been based almost entirely on the paediatric population. Since hypophosphatemic rickets and renal tubular acidosis can result in growth impairment in children, studies in the paediatric population have largely evaluated ifosfamide nephrotoxicity by reporting on indicators of proximal tubular function, specifically glucosuria, amino aciduria, phosphaturia, proteinuria and bicarbonaturia. Many of
Conflict of interest statement
None of the authors have any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within that could inappropriately bias their work.
Acknowledgement
This study was not funded.
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