title: UGT1A1 *6 polymorphism predicts outcome in elderly patients with relapsed or refractory diffuse large B-cell lymphoma treated with carboplatin, dexamethasone, etoposide and irinotecan.
abstract: The uridine diphosphate glucuronosyltransferase (UGT) gene 1A1*6 polymorphism, which affects irinotecan metabolism, has been associated with improved survival in lymphoma patients treated with of carboplatin, dexamethasone, etoposide and irinotecan (CDE-11). This study assessed the efficacy of CDE-11 relative to the UGT1A1*6 polymorphism in 27 elderly patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for high-dose chemotherapy plus autologous stem cell transplantation. The 2-year survival rate after initial CDE-11 treatment was significantly higher in patients with than without UGT1A1*6 (57% vs. 5%). The most common grade 4 adverse event in patients with the UGT1A1*6 genotypes was neutropenia (88.9%), but there were no gastrointestinal adverse events or treatment-related deaths. Disease progression was the most frequent cause of death. CDE-11 was well tolerated and provided clinical benefit to elderly patients with relapsed or refractory diffuse large B-cell lymphoma. The response to CDE-11 likely correlated with UGT1A1*6 polymorphisms, but further prospective studies are warranted to optimize irinotecan-based chemotherapies relative to UGT1A1 polymorphism.
authors: Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-Ku, Fukuoka, 810-8563, Japan, yamas009@kyumed.jp.
authors: Satoshi
authors: S
authors: Yamasaki
authors: Kazuki
authors: K
authors: Tanimoto
authors: Kentarou
authors: K
authors: Kohno
authors: Masanori
authors: M
authors: Kadowaki
authors: Ken
authors: K
authors: Takase
authors: Seiji
authors: S
authors: Kondo
authors: Akira
authors: A
authors: Kubota
authors: Morishige
authors: M
authors: Takeshita
authors: Seiichi
authors: S
authors: Okamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D016190:Carboplatin; D003907:Dexamethasone; D005047:Etoposide; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme