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Treatment of Childhood Sarcoma with Irinotecan: Bilirubin Level as a Predictor of Gastrointestinal Toxicity

Abstract Irinotecan is a promising anticancer agent for the treatment of childhood cancer un-responsive to conventional chemotherapy. Its active metabolite, 7-ethyl-10 hydroxy-camptothecin (SN-38) is glucuronidated by a uridine-diphosphoglucuronosyl-transferase (UGT1A1) to form an inactive metabolite. It was supposed that patientswith the UGT1A1*28 polymorphism would have a greater prevalence of elevated pre-treatment serum bilirubin levels and higher toxicity. The aim of our study was to investigate the predictive value of pre-treatment bilirubin levels in the development of severe diarrhea in solid tumor patients treated with irinotecan. The survey included14 pediatric patients with refractory sarcomas treated with irinotecan (CPT-11). Patients were grouped based on the development of mild (G0-2) or severe (G3) gastrointestinal toxicity. The simple linear regression model and the non-parametric paired wilcoxon test were adopted for the analysis. P <0.05 was judged to indicate a significant difference. The results showed a significant increase in severity of diarrhea with in creasing total pre-treatment bilirubin. Therefore, we propose that pre-treatmentbilirubin levels can predict gastrointestinal toxicity in pediatric cancer.