Abstract
Ifosfamide is an alkylating agent which has been incorporated into frontline therapy for a number of malignant paediatric tumours. Recent data appears to suggest that tubular dysfunction may result from incorporation of this drug into chemotherapy schedules and that toxicity may be dose related. A detailed investigation of renal function was performed in a group of patients, ranging in age from 8 months to 15.9 years (median 8.6 years) with rhabdomyosarcoma (n=11) and Ewing's sarcoma (n=9) who were currently receiving (n=4) or had completed ifosfamide (n=16) therapy a mean of 16 months at the time of study. All but one patient demonstrated some degree of renal dysfunction and toxicity did not necessarily appear to be dose related. Implications for incorporation of this agent into future schedules for childhood sarcomas, which can expect to cure more than 60% of such children, must be addressed. The importance of ongoing monitoring is emphasised.
Similar content being viewed by others
Abbreviations
- GFR :
-
glomerular filtration rate
- α-1mic :
-
α-1 microglobulin
- NAG :
-
N-acetyl-β-d glucosaminidase
References
Brade WP, Herdrick K, Varini M (1985) Ifosfamide pharmacology, safety and therapy potential. Cancer Treat Rev 12:1–47
Brade WP, Hendrich K, Kachel-Fischer U, Arailo CE (1991) Dosing and side effects of ifosfamide plus mesna. J Can Res Clin Oncol 117 [Suppl IV]: A164–186
Brodehl J, Krause A, Hoyer PF (1988) Assessment of maximal tubular phosphate reabsorption: comparison of direct measurement with the nomogram of Bijvoet. Paediatr Nephrol 2:183–189
Ghazali S, Barrett TM (1974) Urinary excretion of calcium and magnesium in children. Arch Dis Child 49:97–101
Goren MP, Wright RK, Horowitz ME, Pratt CB (1987) Ifosfamide-induced subclinical tubular nephrotoxicity despite mensa. Cancer Treatment Reports 71(2):127–130
Goren MP, Pratt CB, Viar MJ (1989) Tubular nephrotoxicity during long term ifosfamide and mesna therapy. Cancer Chemother Pharmacol 25:70–72
Heney D, Wheldon J, Rushworth P, Chapman C, Lewis J, Bailey CE (1991) Progressive renal toxicity due to ifosfamide. Arch Dis Child 66:966–970
Jurgens H, Paulussen M, Roessner A, Harms D, Dunst J, Winklemann W, Weinal P, Gobel U (1992) Primary Ewings sarcoma of bone: update of the CESS experience. Med Pediatr Oncol 20(5):388 70A
Koscielniak E, Jurgens H, Winkler K, Burger D, Herbst M, Keim M, Bernhard G, Treuner J (1992) Treatment of soft tissue sarcoma in childhood and adolescence. Cancer 70:2557–2567
Oberlin O, Haband JL, Zucher JM, Mentigny MB, Terrier-Lacombe MB, Dubousset J, et al. (1992) No benefit of ifosfamide in Ewings sarcoma; a nonrandomized study of the French Society of Paediatric Oncology. J Clin Oncol 10:1407–1412
Pinkerton CR, Rogers H, James C, et al (1985) A phase II study of ifosfamide in children with recurrent solid tumours. Cancer Chemother Pharmacol 15:258–262
Pratt C, Horowitz ME, Meyer WH, et al (1987) Phase II trial of ifosfamide in children with malignant solid tumours. Cancer Treat Rep 71:131–135
Shaw IC, Graham MI (1987) Mesna —a short review. Cancer Treat Rev 14: 67–86
Shaw PJ, Eden T (1990) Ifosfamide in paediatric oncology: tried but not tested? Lancet I:1022–1023
Skinner R, Pearson ADJ, Price L, Coulthand MG, Craft AW (1990) Nephrotoxicity after Ifosfamide. Arch Dis Child 65:732–738
Skinner R, Pearson ADJ, Price L, Coulthand MG, Craft AW (1992) The influence of age on nephrotoxicity following chemotherapy in children. Br J Cancer 66 [Suppl XVIII]:S30-S35
Smetinick J, Verrussel M, Schroder C, Lippen R (1988) Nephrotoxicity associated with ifosfamide. Eur J Paediatr 148:164–166
Stevens M, Flamant F, Rey A, Praquin MJ (1992) Treatment of nonmetastatic rhabdomyosarcoma in the SIOP MMT 89 Study. Med Pediatr Oncol 20(5): 389 73A
Suarez A, McDowell H, Niaudet P, Comoy E, Flamant F (1991) Long term follow up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumours: An International Society of Paediatric Oncology Report. J Clin Oncol 9(12):2177–2182
Wagner T, Zink M, Schwieder G (1987) Influence of mesna and cysteine on the systemic toxicity and therapeutic efficacy of activated cyclophosphamide. J Cancer Res Clin Oncol 113:160–165
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ashraf, M.S., Brady, J., Breatnach, F. et al. Ifosfamide nephrotoxicity in paediatric cancer patients. Eur J Pediatr 153, 90–94 (1994). https://doi.org/10.1007/BF01959214
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01959214