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Background  Uridine 5′‐diphospho‐glucuronosyltransferase 1A1 ( UGT1A1*27 ) is known to impair the effect of  UGT  in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the  UGT1A1*27  polymorphism in irinotecan therapy, we conducted a prospective study.    Methods  Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m 2 ; age ≥ 20; and Eastern Cooperative Oncology Group performance score ( PS)  0–2. Patients were examined for  UGT1A1*28  and  *6  polymorphisms and received irinotecan. When the  UGT1A1*28  polymorphism was detected, a search for  UGT1A1*27  was conducted. Fifty patients were enrolled, with 48 patients determined eligible.    Results   UGT1A1  polymorphisms *28/*28, *6/*6, *28/*6, *28/−, *6/−, −/− observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively.  UGT1A1*27  were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with  UGT1A1*28  and  UGT1A1*6  polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with  UGT1A1*28  polymorphisms compared with wild type (75% vs. 32%,  P  = 0.049; 75% vs. 36%,  P  = 0.039, respectively).    Conclusion  Our prospective study did not locate the  UGT1A1*27  polymorphism, suggesting that  UGT1A1*27  does not significantly predict severe irinotecan toxicity in cancer patients.

thoracic cancer

Prospective study of the  UGT1A1*27  gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu ( LOGIK1004B )