Risk stratification and prevention for trastuzumab-related cardiotoxicity

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu 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
• 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

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).

Free Research Field

循環器内科学

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。