Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas.

Purpose: The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital.

Methods: The authors reviewed the records of 199 patients receiving ICR at St. Jude between June 1986 and December 31, 1994 for evidence of RTT. Their median age was 13.3 years (range 1.2-24.8); 150 patients were white and 112 were male patients. Diagnoses included osteosarcoma (n = 82), Ewing sarcoma (n = 82), rhabdomyosarcoma (n = 28), and a group of other tumors (n = 7).

Results: The authors estimated the proportion of patients with severe RTT during the first five cycles of ICR and within 1 year after therapy for three groups of patients receiving ifosfamide (IFOS, n = 110), ifosfamide/cisplatin (IFOS/CDDP, n = 51), and ifosfamide/carboplatin (IFOS/CARBO, n = 38). The IFOS/CDDP patients received three cycles of IFOS before receiving CDDP and received only 200 mg/m2 by cycle 5, whereas the IFOS/CARBO patients received both agents simultaneously. The authors compared the probability of severe RTT among treatment groups using a generalized linear model for the first five cycles of ICR, as well as the probability of severe RTT within 1 year after therapy among treatment groups for patients receiving all prescribed IFOS using an exact chi-square test with pairwise comparisons when the three-way P value was less than 0.10. The proportion of patients with severe RTT during the first three cycles of ICR was significantly greater in the IFOS/CARBO group than in the other two. Although the proportion of patients with severe RTT in the IFOS/CDDP group increased during cycles 4/5, the proportion of patients with severe RTT remained significantly greater in the IFOS/ CARBO group. Within 1 year after therapy, the proportion of patients with severe RTT differed among the three groups, and pairwise comparisons revealed a significant difference between the IFOS and the IFOS/CDDP group. Severe RTT developed in four IFOS/CDDP patients more than 1 year after therapy, suggesting a long-term effect of CDDP on tubular function.

Conclusions: Chemotherapy regimens including IFOS/ CARBO produce severe acute RTT more frequently than regimens including IFOS or IFOS/CDDP. Patients receiving IFOS/ CDDP appear at risk for delayed RTT. Long-term follow-up of these patients is essential to assess whether the number of patients receiving IFOS/CDDP with severe RTT continues to increase over time and to evaluate the long-term significance of these abnormalities.