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J. Kishimoto
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-055 - Prospective Study of UGT1A1*27 Gene Polymorphism for Irinotecan Therapy: Result of Lung Oncology Group in Kyushu (LOGiK1004B) (ID 675)
09:30 - 09:30 | Author(s): J. Kishimoto
- Abstract
Background:
UGT1A1*27 is known that exist together with UGT1A1*28 as linkage disequilibrium and impair the effect of UDP-glucuronosyltransferase (UGT) in basic research, however, poor clinical investigation because of the rare frequency. The aim of this study is to evaluate the effect of UGT1A1*27 gene polymorphism for safety and efficacy in irinotecan therapy.
Methods:
Eligibility criteria were: lung cancer patients; scheduled the dose of irinotecan therapy as single ≥ 80 mg/m[2], combination ≥ 50 mg/m[2], radiation with single ≥ 50 mg/m[2], radiation with combination ≥ 40 mg/m[2]; age ≥ 20 years; performance status 0-2. After informed consents, patients were enrolled and collected the blood to examine UGT1A1*28 and UGT1A1*6 polymorphism and received irinotecan therapy. Examination of UGT1A1*27 were added when founding UGT1A1*28 polymorphism. We planned 111 enrollment for an accrual of 10 patients with UGT1A1*27 gene polymorphism.
Results:
Fifty patients were enrolled in this trial between October 2011 and December 2013. Two patients judged protocol violation. Remaining 48 were evaluated. UGT1A1 gene polymorphisms *28/*28, *6/*6, *28/*6, *28/-, *6/-, -/- observed 0, 1, 1, 7, 17 and 22, respectively. UGT1A1*27 were analyzed in 9 patients including ineligible one patients with *28/*28, however, no UGT1A1*27 gene polymorphism was found and the study was stopped. A total of 153 times of irinotecan therapy were administered with a median of 3 times per one patient: 1 time in 7 patients (15%), 2 times in 9 (19%), 3 in 19 (40%), 4 in 3 (6%), 5 in 1 (2%), and 6 in 9 (19%). Irinotecan were used as combination chemotherapy in 32 (67%) patients, with cisplatin in 12 (25%), carboplatin in 10 (21%), gemcitabine in 9 (19%), paclitaxel in 1 (2%). In remaining 16 patients (33%), only irinotecan single therapy were administered. Radiotherapies were administered concurrently in 23 (48%) patients with median 60 (range 40-61.4) Gy. Febrile neutropenia were observed higher tendency in patients with UGT1A1*6 (32%) and UGT1A1*28 (25%) gene polymorphism compare with wild type (14%) but had no significant difference. Grade 3/ 4 leukopenia and neutropenia were observed in 6 out of 8 patients with UGT1A1*28 gene polymorphism and significant higher compare with wild type (75% vs. 32%, p=0.049; 75% vs. 36%, p=0.039, respectively). The other toxicities have no difference between UGT1A1 gene polymorphism and wild type. There was no pneumonitis and treatment-related death. Tumor response was not evaluated because not included endpoints. Median PFS of 48 patients was 6.8 months and the 1- and 2-year survival rates were 20.8%. Median PFS separated by UGT1A1 gene polymorphisms were 10.1 months in UGT1A1*28 heterozygous, 8.5 months in UGT1A1*6 heterozygous, and 6.8 months in both wild type, respectively. Median OS of 48 patients was 15.7 months and the 1- and 2-year survival rates were 57.7% and 40.3%, respectively. Median OS separated by UGT1A1 gene polymorphisms were not reached in in UGT1A1*28 heterozygous, 16.4 months in UGT1A1*6 heterozygous, and 12.3 months in wild type, respectively.
Conclusion:
UGT1A1*27 gene polymorphism was not found in our methods. Further investigation might be warranted in patients with UGT1A1*28 wild type.
