UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma.

摘要: BACKGROUND It is known that the uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1)*28 polymorphism reduces UGT1A1 enzyme activity, which may lead to severe toxicities in patients who receive irinotecan. This study was conducted assess influence of this on efficacy and toxicity irinotecan treatment Chinese with metastatic colorectal carcinoma (CRC). METHODS In total, 128 CRC had received previous plus 5-fluorouracil/leucovorin were analyzed retrospectively. Genomic DNA samples obtained from patients' leukocytes, genotypes determined by analyzing sequence TATA boxes gene. The UGT1A1*28 outcome analyzed. RESULTS Approximately 20% identified polymorphism, including 15.6% (n = 20 patients) thymine-adenine (TA)6/TA7 genotype 4.7% 6 TA7/TA7 genotype. remaining 79.7% 102) wild type TA6/TA6. Marked increases grade 3 or 4 neutropenia (53.8% vs 4.9%; P < .01), neutropenic fever (38.5% 3.9%; diarrhea (26.9% 5.9%; pretreatment bilirubin level (23.1% 8.8%; .04) observed TA6/TA7 genotypes. Patients' levels correlated well irinotecan-induced (P .01). It noted that, although requirement for dose reduction significantly greater genetic variant (42.3% 12.7%; it did not affect response rate irinotecan-based chemotherapy 45.1%; .80), progression-free survival (10 months 11 months; .94) overall (19 18 .84). CONCLUSIONS The current data suggested be a key determinant predicting without affecting CRC. Further prospective studies are warranted using optimize chemotherapy. Cancer 2008. © 2008 American Society.