Young age and the risk for ifosfamide-induced nephrotoxicity: a critical review of two opposing studies

Ifosfamide has been in use as an effective antineoplastic agent for solid tumors in both children and adults since the late 1960s. Although some adverse effects (e.g. hemorrhagic cystitis) can be overcome by the co-administration of 2-mercaptoethanesulfonate (MESNA), others such as nephrotoxicity cannot. There is a consensus that factors such as the cumulative dose of ifosfamide and concomitant cisplatin administration may influence not only the incidence but also the severity of ifosfamide-induced renal toxicity. Several preliminary studies suggested young age as a risk factor for nephrotoxicity; however, there is little agreement on this. The reasons for this uncertainty may include sample size, study design, dose and differences in renal function assessment. In this review we examine the two largest cohort studies conducted in pediatric patients. One study suggests that ifosfamide-induced renal toxicity is age- related, whereas analysis of the other failed to show age as an important predictor for ifosfamide-induced renal toxicity. The studies differed in design, end-points of toxicity and concomitant drug therapy. Due to the effectiveness of ifosfamide as an antineoplastic agent, it is important that an understanding of the factors that predispose pediatric patients to ifosfamide-induced nephrotoxicity be obtained.