Treatment of childhood sarcoma with irinotecan: bilirubin level as a predictor of gastrointestinal toxicity.
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
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Division of Pediatric Oncology, Catholic University, Rome, Italy. ruggiero@rm.unicatt.it
Coccia
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Scalzone
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Attinà
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Riccardi
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D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000097:blood / Q000139:chemically induced*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000187:drug effects; D000077146:Irinotecan; D008297:Male; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D001663:Bilirubin; D002166:Camptothecin