Association of ATP-Binding Cassette, Sub-family C, Number 2 (ABCC2) Genotype with Pharmacokinetics of Irinotecan in Japanese Patients with Metastatic Colorectal Cancer Treated with Irinotecan Plus Infusional 5-Fluorouracil/Leucovorin (FOLFIRI)(Miscellaneo

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概要

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• ATP-binding cassette, sub-family C, number 2 (ABCC2) is involved in the biliary excretion of irinotecan and its metabolites, SN-38 and SN-38 glucuronide. Effects of the ABCC2 genotype on the pharmacokinetics (PK) of irinotecan and the metabolites were examined in Japanese patients with metastatic colorectal cancer receiving irinotecan plus infusional 5-fluorouracil/leucovorin (FOLFIRI). ABCC2 genotypes (-1549G>A, -1023G>A, -1019A>G, -24C>T, 1249G>A and 3972C>T) and haplotypes were analyzed for 67 patients with cancer. PK was also examined in a subset of 31 patients receiving FOLFIRI. Relationship between the ABCC2 genotypes or diplotypes and area under the time-concentration curve (AUC) of irinotecan and the metabolites normalized by irinotecan dose was analyzed. The lower AUC of irinotecan was seen in patients with A/A or G/A genotypes at 1249 of the ABCC2 gene than others (p=0.011, Mann-Whitney U teat). AUC of SN-38 in patients with A/A or G/A genotypes at -1023 was significantly lower than that in others (p=0.018). The haplotype I included -1023A (GA__-ACGC) was the most frequent one with the allele frequency of 0.366. The AUC of SN-38 observed in patients with diplotypes harboring at least one haplotype I was lower than that observed in others (p=0.023). The haplotype IV consisted of 1249 (GGACA__-C) and was the fourth most frequent one with the allele frequency of 0.127. Patients with diplotypes carrying at least one haplotype IV showed lower AUC of irinotecan than others (p=0.011). Thus, ABCC2 genotype is one of the predictors of the variability of irinotecan PK in Japanese patients with metastatic colorectal cancer receiving FOLFIRI.

• 2008-11-01

著者

• Araki Kazuhiro

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Tanaka Ryuhei

  Department Of Cardiology Gifu Prefectural General Medical Center

• Tanaka Ryuhei

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• MIZUNO Keiko

  Department of Diagnostic Pathology, Kochi Red Cross Hospital

• ANDO Yuichi

  Department of Organ Transplantation and Surgery,Institute of Medical Science,University of Tokyo

• Mizuno Keiko

  Department Of Biological And Chemical Engineering Faculty Of Engineering Gunma University

• Mizuno Keiko

  Department Of Medical Oncology Saitama International Medical Center-comprehensive Cancer Center Sait

• FUJITA Ken-ichi

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• YAMAMOTO Wataru

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• ENDO Hisashi

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• NAGASHIMA Fumio

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• ICHIKAWA Wataru

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• MIYA Toshimichi

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• SUNAKAWA Yu

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• NARABAYASHI Masaru

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• AKIYAMA Yuko

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• KAWARA Kaori

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• SASAKI Yasutsuna

  Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University

• YAMASHITA Keishi

  Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center Sai

• ISHIDA Hiroo

  Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center Sai

• MATSUNAGA Mototsugu

  Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center Sai

• Kawara Kaori

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Sunakawa Yu

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Yamashita Keishi

  Department Of Medical Oncology Saitama International Medical Center-comprehensive Cancer Center Sait

• Fujita Ken-ichi

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Miya Toshimichi

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Endo Hisashi

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Sasaki Yasutsuna

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Sasaki Yasutsuna

  Department Of Clinical Oncology And Medical Oncology International Medical Center Saitama Medical Un

• Narabayashi Masaru

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Ando Yuichi

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Ishida Hiroo

  Department Of Medical Oncology Saitama International Medical Center-comprehensive Cancer Center Sait

• Akiyama Yuko

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Nagashima Fumio

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Nagashima Fumio

  Department Of Mechanical Engineering Keio University

• Fujita Ken-ichi

  Department Of Biology And Geosciences Graduate School Of Science Osaka City University

• Ichikawa Wataru

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Ando Yuichi

  Department Of Clinical Oncology And Chemotherapy Nagoya University Hospital

• Matsunaga Mototsugu

  Department Of Medical Oncology Saitama International Medical Center-comprehensive Cancer Center Sait

• Yamamoto Wataru

  Department Of Medical Oncology Comprehensive Cancer Center Saitama Medical University

• Yamamoto Wataru

  Department Of Hematology Yokohama City University Medical Center

• Yamamoto Wataru

  Department Of Hematology Yamato City Hospital

• Nagashima Fumio

  Department Of Internal Medicine Medical Oncology Kyorin University School Of Medicine

• ENDO HISASHI

  Department of Internal Medicine, National Shikoku Cancer Center

• ICHIKAWA Wataru

  Department of Clinical Oncology and Medical Oncology, International Medical Center, Saitama Medical University

• MIZUNO Keiko

  Department of Biochemistry, Tokushima University, School of Medicine

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