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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.
AuthorsSatoshi Yamasaki, Kazuki Tanimoto, Kentarou Kohno, Masanori Kadowaki, Ken Takase, Seiji Kondo, Akira Kubota, Morishige Takeshita, Seiichi Okamura
JournalAnnals of hematology (Ann Hematol) Vol. 94 Issue 1 Pg. 65-9 (Jan 2015) ISSN: 1432-0584 [Electronic] Germany
PMID25055799 (Publication Type: Journal Article)
Chemical References
  • Etoposide
  • Irinotecan
  • Dexamethasone
  • Carboplatin
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Camptothecin
Topics
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
  • Camptothecin (administration & dosage, analogs & derivatives)
  • Carboplatin (administration & dosage)
  • Dexamethasone (administration & dosage)
  • Etoposide (administration & dosage)
  • Female
  • Follow-Up Studies
  • Glucuronosyltransferase (genetics)
  • Humans
  • Irinotecan
  • Lymphoma, Large B-Cell, Diffuse (diagnosis, drug therapy, genetics)
  • Male
  • Middle Aged
  • Polymorphism, Genetic (genetics)
  • Prospective Studies
  • Recurrence
  • Treatment Outcome

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