2003 Fiscal Year Final Research Report Summary
ESTABLISHMENT OF PERSONALIZED CHEMOTHERAPY OF LUNG CANCER APPLYING PHARMACOGENOMICS
| Project/Area Number |
14370196
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
SHIMOKATA Kaoru Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10022906)
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Yoshinori Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20270986)
SEKIDO Yoshitaka Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (00311712)
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| Project Period (FY) |
2002 – 2003
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| Keywords | cancer / chemotherapy / tailor-made therapy / polymorphism / enzyme / clinical study / irinotecan |
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| Research Abstract |
Although irinotecan is widely used as an anticancer drug, it causes unpredictably severe, occasionally fatal toxicity of leukopenia or diarrhea. Irinotecan is metabolized to form active SN-38,which is further conjugated and detoxified by UDP-glucuronosyltransferase1A1(UGT1A1) enzyme. Genetic polymorphism of the UCT1A1 would affect an interindivisual variation of the toxicity by irinotecan via the alternation of bioavailability of SN-38. We investigated whether the variant UGT1A1 genotypes would be at higher risk for severe toxicity by imotcan. We suggested that determination of the UGT1A1 genotypes might be clinically useful for predicting severe toxicity by irinotecan in cancer patients.
We studied the relationship between genetic polymorphisms of the UGT1A7 gene and irinotecan toxicity in Japanese cancer patients. The results suggested that determination of UGT1A7 genotypes would not be useful for predicting severe toxicity of irinotecan.
We proposed phase 1 study of irinotecan according to the polymorphism of UGT1A1^*28. The Ethical Committee and IRB in the Nagoya University approved the clinical study. When there are homo-or hetero-polymorphism of UGT1A1^*28,the dose of irinotecan was decreased at half level, and no severe side effects were not observed. Determination of polymorphism of UGT1A1^*28,prior irinotecan chemotherapy would be useful.
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