The growing pains of ifosfamide

Abstract

Ifosfamide is a commonly used chemotherapeutic known to have numerous adverse kidney manifestations. In this issue of Clinical Kidney Journal, Ensergueix et al. report a multicentric observational retrospective French study on 34 adult patients with tubular dysfunction and /or kidney dysfunction following ifosfamide treatment. Of these patients, 18% had isolated proximal tubular dysfunction, 14% had isolated acute kidney injury (AKI), 18% had isolated chronic kidney disease (CKD) and 50% had a combination of proximal tubular dysfunction and AKI. Concomitant treatment with cisplatin was identified as a risk factor for the development of AKI, and cisplatin and age were associated with estimated glomerular filtration rate at last follow-up. Interestingly, the cumulative dose of ifosfamide was not associated with renal outcomes. This report highlights the need for additional studies on the prevalence, spectrum and management of ifosfamide-associated nephrotoxicity and clearly demonstrates that patients who received ifosfamide should be followed long term to detect proximal tubular dysfunction and CKD early.

Continuous 14 Day Infusional Ifosfamide for Management of Soft-Tissue and Bone Sarcoma: A Single Centre Retrospective Cohort Analysis

“…High-dose ifosfamide (>9 g/m 2 /cycle) is an active agent but its use can be challenging, particularly in the palliative setting, because of toxicities including myelosupression, nephrotoxicity and neurotoxicity. One attempt to mitigate these toxicities is through the use of continuous infusional ifosfamide [ 6 , 7 , 8 ], which can be administered via a continuous ambulatory delivery device (CADD) [ 9 ], concurrently with mesna to minimise the risk of urothelial toxicity [ 10 , 11 ]. In addition to better tolerability, it has been proposed that this delivery method may possess superior cytotoxicity [ 12 ] and can be used as an outpatient regimen, whereas conventional fractionated ifosfamide is predominantly used in the ambulatory setting.…”

“…Patients had either oligometastatic disease (four patients) or local recurrence (five patients) with SS (four patients) and ES (two patients) the most common histological subtypes treated. The median number of cycles of infusional ifosfamide given was five (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], and all patients achieved disease control either with radiological and/or metabolic improvement (67%) or stable disease (33%). Median OS for these patients at the date of analysis was 24 m (range 12-32).…”

Innovative approaches for treatment of osteosarcoma

“…16,27 Ifosfamide, (IFO), a bifunctional alkylating agent, is a member of the nitrogen mustard family and has been used to treat several tumor types including lymphoblastic leukemia, soft-tissue sarcoma, and OS. 29,30 Its common cumulative dose starts from 480 to 600 mg/m 2 ; dose per cycle is from 100 to 120 mg/m 2 . 5 The drug's mechanism of action is through the cross-linking of DNA strands, inhibition of DNA synthesis, and protein translation.…”

“…16 IFO also has dramatic side effects such as hemorrhagic cystitis, acute kidney injury, Fanconi's syndrome, interstitial nephritis, glomerular disease, and encephalopathy. 16,29…”

Investigation of Ifosfamide Toxicity Induces Common Upstream Regulator in Liver and Kidney

“…Although ifosfamide is relatively well tolerated compared to other toxic alkylating agents, it is known to be associated with numerous life-threatening adverse effects that limit its clinical use [2]. The major side effects of ifosfamide include severe renal injury resulting from reactive toxic species from ifosfamide, including acute kidney injury, interstitial nephritis, hemorrhagic cystitis, and Fanconi syndrome [3]. In clinics, severe multiple organ toxicity was reported in patients who experienced early renal toxicity, and repeated high-dose ifosfamide-induced one organ failure that led to subsequent organ failure [4,5].…”