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Risk stratification and prevention for trastuzumab-related cardiotoxicity

Research Project

Project/Area Number 16K09442
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKyushu University

Principal Investigator

Ohtani Kisho  九州大学, 医学研究院, 講師 (60380408)

Co-Investigator(Kenkyū-buntansha) 肥後 太基  九州大学, 医学研究院, 助教 (10457426)
井手 友美  九州大学, 医学研究院, 准教授 (90380625)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsトラスツズマブ / アントラサイクリン / 心毒性 / 心機能障害 / 心機能回復 / 心不全治療 / 乳癌 / 抗癌剤 / 抗癌剤誘発心筋症
Outline of Final Research Achievements

We retrospectively studied 160 patients with breast cancer receiving trastuzumab in the adjuvant (n=129) as well as metastatic (n=31) settings in our institution from 2006 to 2015. During the median follow-up of 3.5 years, 20 patients (15.5%) receiving adjuvant trastuzumab and 7 patients (22.6%) with metastatic breast cancer developed trastuzumab-related cardiotoxicity with a mean decrease in LV ejection fraction (EF) of 19.8 %. By the multivariate analysis, lower LVEF before trastuzumab (OR, 1.30; 95% CI, 1.16 to 1.48; P=0.0001) independently predicted subsequent development of trastuzumab-related cardiotoxicity. LV systolic dysfunction was reversible in 20 patients (74.1 %) with a median time to recovery of 7 months, which was independently associated with lower dose of anthracyclines (OR, 1.03; 95% CI, 1.01-1.07, P=0.020) and an introduction of renin-angiotensin inhibitors and β-blockers (OR, 19.0; 95% CI, 1.00-592.2, P=0.034).

Academic Significance and Societal Importance of the Research Achievements

欧米では、がん領域と循環器領域で診療科の垣根を越え、連携して診療にあたるOnco-cardiology(腫瘍心臓病学)という新たな学際領域が生まれ、基礎、臨床、疫学研究の総合的な取り組みが行われているが、その心毒性に関する実態報告は本邦から皆無であり、大きく後れをとっている。そこで実態調査を行い、本邦独自の抗がん剤心毒性の臨床像および、早期発見、治療介入が心機能回復につながることを初めて明らかにした画期的な研究と考えられ、報告した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Recovery from left ventricular dysfunction was associated with the early introduction of heart failure medical treatment in cancer patients with anthracycline-induced cardiotoxicity2019

    • Author(s)
      Ohtani K, Fujino T, Ide T, Funakoshi K, Sakamoto I, Hiasa KI, Higo T, Kamezaki K, Akashi K, Tsutsui H.
    • Journal Title

      Clin Res Cardiol.

      Volume: ahead of print Issue: 6 Pages: 600-611

    • DOI

      10.1007/s00392-018-1386-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cardioprotective effect of renin-angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity.2019

    • Author(s)
      Ohtani K, Fujino T, Ide T, Funakoshi K, Sakamoto I, Hiasa KI, Higo T, Kamezaki K, Akashi K, Tsutsui H.
    • Journal Title

      Clin Res Cardiol.

      Volume: ahead of print Issue: 10 Pages: 1128-1139

    • DOI

      10.1007/s00392-019-01448-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] がん治療と心不全の疫学から考える心エコー検査適応2018

    • Author(s)
      大谷規彰
    • Organizer
      第 27 回日本心エコー図学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] トラスツズマブ関連心筋症2017

    • Author(s)
      大谷規彰
    • Organizer
      第114回日本内科学会講演会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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