Novel strategy for prediction of toxicity and efficacy of chemotherapy for patients with metastatic colorectal cancer.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591725
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: HAZAMA Shoichi 山口大学, 大学院・医学系研究科, 准教授 (50253159)
• Co-Investigator(Kenkyū-buntansha): OKAYAMA Naoko 山口大学, 医学部附属病院, 副臨床・衛生検査技師長 (40420541) ; SAKAMOTO Kazuhiko 山口大学, 医学部附属病院, 助教 (50420526)
• Project Period (FY): 2009 – 2011
• Keywords: イリノテカン / セツキシマブ / UGT1A1 / KRAS / BRAF / PI3K

Research Abstract

1. The toxicity of irinotecan, G3/ 4 neutropenia, was predicted by UGT1A1^* 28/^* 6 alleles as well as UGT1A7 N129K(G),-57(G), UGT1A9^* 22 alleles. Genotype subset selection of multi-UGT1As polymorphisms can predict severe neutropenia and tumor responses of metastatic CRC patients received FOLFIRI regimen.
2. Mutations such as BRAF, and PI3K were also important biomarkers of cetuximab. Furthermore, our date suggest that the FcGR3_a polymorphisms may be also useful molecular markers to predict clinical outcome in mCRC pts treated with cetuximab.

Research Products

• [Journal Article] Cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer : results from the randomised phase II part of a phase I/ II study (2011)
  • Author(s): Kato T, Muro K, Yamaguchi K, Bando H, Hazama S, Amagai K, Baba H, Denda T, Shi X, Fukase K, Sakamoto J, Mishima H
  • Journal Title: Ann Oncol Volume: 23(4): 933-41
  • Peer Reviewed
• [Journal Article] Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity (2011)
  • Author(s): Maeda K, Hazama S, Tokuno K, Kan S, Maeda Y, Watanabe Y, Kamei R, Shindo Y, Maeda N, Yoshimura K, Yoshino S, Oka M
  • Journal Title: Anticancer Res Volume: 31(12): 4569-74
  • Peer Reviewed
• [Journal Article] Prospective phase II study of FOLFIRI for mCRC in Japan, including the analysis of UGT1A1 28/ 6 polymorphisms (2011)
  • Author(s): Okuyama Y, Hazama S, Nozawa H, Kobayashi M, Takahashi K, Fujikawa K, Kato T, Nagata N, Kimura H, Oba K, Sakamoto J, Mishima H
  • Journal Title: Jpn J Clin Oncol Volume: 41(4): 477-82
  • Peer Reviewed
• [Journal Article] Importance and practice of UGT1A1 polymorphisms (2011)
  • Author(s): Hazama S, Oka M
  • Journal Title: Nihon Rinsho Volume: 69Suppl3 : 351-4
• [Journal Article] The importance of evaluation of DNA amplificability in KRAS mutation testing with dideoxy sequencing using formalin-fixed and paraffin-embedded colorectal cancer tissues (2010)
  • Author(s): Okayama N, Nishioka M, Hazama S, Sakai K, Suehiro Y, Maekawa M, Sakamoto J, Iwamoto S, Kato T, Mishima H, Oka M, Hinoda Y
  • Journal Title: Jpn J Clin Oncol Volume: 41(2): 165-71
  • Peer Reviewed
• [Journal Article] Phase I study of irinotecan and doxifluridine for metastatic colorectal cancer focusing on the UGT1A1^* 28 polymorphism (2009)
  • Author(s): Hazama S, Nagashima A, Kondo H, Yoshida S, Shimizu R, Araki A, Yoshino S, Okayama N, Hinoda Y, Oka M
  • Journal Title: Cancer Sci Volume: 101(3): 722-7
  • Peer Reviewed
• [Journal Article] Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells (2009)
  • Author(s): Ueno K, Hazama S, Mitomori S, Nishioka M, Suehiro Y, Hirata H, Oka M, Imai K, Dahiya R, Hinoda Y
  • Journal Title: Br J Cancer Volume: 101(8): 1374-81
  • Peer Reviewed
• [Presentation] 大腸がん治療新時代Personalized Therapyの現状と今後UGT1As遺伝子多型で予測するIrinotecanの毒性と効果 (2010)
  • Author(s): 硲彰一, 日野田裕治, 三嶋秀行, 坂本純一, 岡正朗
  • Organizer: 日本癌治療学会
  • Place of Presentation: 京都国立京都国際会館
  • Year and Date: 2010-10-29
• [Presentation] 消化器癌化学療法の効果予測(抗癌剤感受性試験など)新しい遺伝子多型解析による大腸癌化学療法(FOLFIRI)の効果予測システムの開発 (2009)
  • Author(s): 硲彰一, 三嶋秀行, 加藤健志, 高橋賢一, 野澤寛, 木村文彦, 安藤秀明, 小林道也, 坂本純一, 岡正朗
  • Organizer: 日本臨床外科学会
  • Place of Presentation: 京都国立京都国際会館
  • Year and Date: 2009-11-21
• [Presentation] UGTIA多型の遺伝子型サブセット選択はFOLFIRI投与mCRC患者の毒性及び腫瘍反応性を予測する(Genotype subset selection of UGTIAs polymorphisms can predict toxicity and tumor response of mCRC pts received FOLFIRI)(英語) (2009)
  • Author(s): 硲彰一, 日野田裕治, 岡山直子, 浜本義彦, 藤田悠介, 三嶋秀行, 坂本純一, 岡正朗
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2009-10-03