Irinotecan is a promising anticancer agent for the treatment of childhood cancer unresponsive to conventional chemotherapy. Its active metabolite, 7-ethyl-10 hydroxycamptothecin (SN-38) is glucuronidated by a uridine-diphosphoglucuronosyltransferase (UGT1A1) to form an inactive metabolite. It was supposed that patients with the UGT1A1*28 polymorphism would have a greater prevalence of elevated pretreatment 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 included 14 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 increasing total pre-treatment bilirubin. therefore, we propose that pre-treatment bilirubin levels can predict gastrointestinal toxicity in pediatric cancer.
Ruggiero, A., Coccia, P., Scalzone, M., Attinà, G., Riccardi, R., Treatment of childhood sarcoma with irinotecan: bilirubin level as a predictor of gastrointestinal toxicity., <<JOURNAL OF CHEMOTHERAPY>>, 2009; 21 (6): 693-697. [doi:10.1179/joc.2009.21.6.693] [http://hdl.handle.net/10807/16877]
Treatment of childhood sarcoma with irinotecan: bilirubin level as a predictor of gastrointestinal toxicity.
Ruggiero, Antonio;Coccia, Paola;Scalzone, Maria;Riccardi, Riccardo
2009
Abstract
Irinotecan is a promising anticancer agent for the treatment of childhood cancer unresponsive to conventional chemotherapy. Its active metabolite, 7-ethyl-10 hydroxycamptothecin (SN-38) is glucuronidated by a uridine-diphosphoglucuronosyltransferase (UGT1A1) to form an inactive metabolite. It was supposed that patients with the UGT1A1*28 polymorphism would have a greater prevalence of elevated pretreatment 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 included 14 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 increasing total pre-treatment bilirubin. therefore, we propose that pre-treatment bilirubin levels can predict gastrointestinal toxicity in pediatric cancer.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.