TY - JOUR
T1 - Renal toxicity of ifosfamide in pilot regimens of the intergroup rhabdomyosarcoma study for patients with gross residual tumor
AU - Intergroup Rhabdomyosarcoma Study Committee of the Childrens Cancer Group
AU - Raney, Beverly
AU - Ensign, Lisa G.
AU - Foreman, John
AU - Khan, Fareed
AU - Newton, William
AU - Ortega, Jorge
AU - Ragab, Abdelsalam
AU - Wharam, Moody
AU - Wiener, Eugene
AU - Maurer, Harold
AU - Andrassy, Richard
AU - Crist, William
AU - Donaldson, Sarah
AU - Fryer, Christopher
AU - Gehan, Edmund
AU - Hammond, Denman
AU - Hays, Daniel
AU - Heyn, Ruth
AU - Lawrence, Walter
AU - Lobe, Thorn
AU - Ruymann, Frederick
AU - Tefft, Melvin
AU - Triche, Timothy
AU - Vietti, Teresa
AU - Webber, Bruce
PY - 1994/11
Y1 - 1994/11
N2 - Purpose The purpose of this review is to characterize the nephrotoxicity noted in newly diagnosed patients under 21 years of age after treatment with ifosfamide-containing chemotherapy regimens and local irradiation for localized gross residual rhabdomyosarcoma or undifferentiated sarcoma.: Patients and Methods From 1987 to 1991, 194 previously untreated patients received vincristine and ifosfamide plus dactinomycin or etoposide for 1–2 years. Ifosfamide was given at 1.8 g/m2/day for 5 days with sodium mercaptoethane sulfonate, or 9 g/m2of ifosfamide per course. The three-drug regimen was repeated every 3–4 weeks.: Results Twenty-eight patients (14%) developed renal toxicity: 19 had renal tubular dysfunction (RTD) characterized by low serum phosphate (≤ 3 mg/dl) or bicarbonate (≤ 20 mEq/L) levels, five had decreased glomerular function (DGF), and four had both RTD and DGF. When nine or more courses of ifosfamide (≥72 g/m2) were given, children <3 years of age had a higher incidence of RTD than did children ≥ 3 years of age (34% versus 6%; p < 0.001). A similar age difference was observed even when eight or fewer courses (≤72 g/m2) were given (p = 0.03). A matched case-control comparison showed that renal abnormalities at diagnosis, chiefly hydronephrosis, also increased the risk of renal tubular injury by ifosfamide by a factor of 13 (p < 0.001). Patients with DGF tended to be older than those with RTD, and all but one received > 72 g/m2of ifosfamide.: Conclusions Patients who are <3 years of age who receive more than eight courses (>72 g/m2) of ifosfamide and who have a preexisting renal abnormality have an increased risk of RTD and DGF. The renal function of patients being considered for ifosfamide treatment must be carefully monitored. Ifosfamide should be avoided in patients with renal abnormalities at diagnosis unless the potential benefit clearly exceeds the risk of further renal impairment.
AB - Purpose The purpose of this review is to characterize the nephrotoxicity noted in newly diagnosed patients under 21 years of age after treatment with ifosfamide-containing chemotherapy regimens and local irradiation for localized gross residual rhabdomyosarcoma or undifferentiated sarcoma.: Patients and Methods From 1987 to 1991, 194 previously untreated patients received vincristine and ifosfamide plus dactinomycin or etoposide for 1–2 years. Ifosfamide was given at 1.8 g/m2/day for 5 days with sodium mercaptoethane sulfonate, or 9 g/m2of ifosfamide per course. The three-drug regimen was repeated every 3–4 weeks.: Results Twenty-eight patients (14%) developed renal toxicity: 19 had renal tubular dysfunction (RTD) characterized by low serum phosphate (≤ 3 mg/dl) or bicarbonate (≤ 20 mEq/L) levels, five had decreased glomerular function (DGF), and four had both RTD and DGF. When nine or more courses of ifosfamide (≥72 g/m2) were given, children <3 years of age had a higher incidence of RTD than did children ≥ 3 years of age (34% versus 6%; p < 0.001). A similar age difference was observed even when eight or fewer courses (≤72 g/m2) were given (p = 0.03). A matched case-control comparison showed that renal abnormalities at diagnosis, chiefly hydronephrosis, also increased the risk of renal tubular injury by ifosfamide by a factor of 13 (p < 0.001). Patients with DGF tended to be older than those with RTD, and all but one received > 72 g/m2of ifosfamide.: Conclusions Patients who are <3 years of age who receive more than eight courses (>72 g/m2) of ifosfamide and who have a preexisting renal abnormality have an increased risk of RTD and DGF. The renal function of patients being considered for ifosfamide treatment must be carefully monitored. Ifosfamide should be avoided in patients with renal abnormalities at diagnosis unless the potential benefit clearly exceeds the risk of further renal impairment.
KW - Ifosfamide
KW - Renal toxicity
KW - Rhabdomyosarcoma in childhood
UR - http://www.scopus.com/inward/record.url?scp=0028171607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028171607&partnerID=8YFLogxK
M3 - Article
C2 - 7978043
AN - SCOPUS:0028171607
SN - 1077-4114
VL - 16
SP - 286
EP - 295
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
IS - 4
ER -