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Safety evaluation of tooth extraction and establishment of predictive biomarkers for delayed healing in patients treated with antiangiogenic drugs

Research Project

Project/Area Number 19K19219
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHokkaido University (2022)
Hokkaido Cancer Center(Department of Clinical Research) (2019-2021)

Principal Investigator

Imamachi Kenji  北海道大学, 歯学研究院, 助教 (40779873)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords血管新生阻害薬 / 抜歯 / 創傷治癒遅延 / 薬剤関連顎骨壊死 / 治癒遅延 / 創傷治癒 / 創傷治癒不全
Outline of Research at the Start

血管新生阻害薬投与中の抜歯における創傷治癒遅延については、未だ不明な点が多い。血管新生阻害薬の休薬などはがん治療そのものへのデメリットとなりうるため、抜歯時の不要な休薬が回避できれば、がん患者にとって大きなメリットになると考える。研究は2期に大別し、第Ⅰ期は過去に血管新生阻害薬投与中で抜歯を施行した患者を対象に、診療録等を用いた後ろ向き研究を行う。第Ⅱ期は血管新生阻害薬投与中で感染など臨床的に抜歯が必要と判断した患者に対し、休薬下での抜歯もしくは投与継続下での抜歯に振り分け、それぞれについて治癒経過に関する調査や、骨治癒に関与しているHMGB1タンパク発現解析などの基礎的研究を行う。

Outline of Final Research Achievements

We investigated tooth extraction in cancer patients receiving bevacizumab (BV). There was no significant difference in post-extraction adverse events between tooth extraction with BV continuation and tooth extraction with BV suspension. In the study of risk factors, concomitant use of taxane anticancer drugs significantly increased risk. The risk was also significantly increased in mandibular molars and surgical tooth extraction with bone removal. In addition, while accumulating cases, we found 3 cases of spontaneous osteonecrosis of the jaw (drug-related osteonecrosis of the jaw: MRONJ) without tooth extraction during administration of BV. In none of the cases was concomitant use of bone-modifying drugs, and the site of occurrence was the mandibular molar region, the maxillary molar region, and the palate prominence, respectively. Concomitant use of taxane anticancer drugs was reported in 2 of the 3 cases.

Academic Significance and Societal Importance of the Research Achievements

これまで、血管新生阻害薬投与中の患者において、抜歯が必要になった際に休薬期間はどの程度必要なのか、そもそも休薬自体必要なのかなど不明な点が多いのが現状であった。血管新生阻害薬の休薬はがん治療そのものへのデメリットとなりうるため、徒に全ての抜歯症例で休薬するのではなく、症例によって抜歯前の不要な休薬が回避しうることが判明したのは社会的意義が大きいものと考えられる。本研究の成果は、がん患者に対する安全な歯科医療の提供に寄与することが期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Antiresorptive Agent-related Osteonecrosis of the Jaw in the Elderly with Dementia and Breast Cancer: A Case Report2021

    • Author(s)
      IMAMACHI Kenji、HATA Hironobu、KAMAGUCHI Mayumi、KITAGAWA Yoshimasa
    • Journal Title

      Journal of Japanese Society of Oral Medicine

      Volume: 27 Issue: 1 Pages: 21-25

    • DOI

      10.6014/jjsom.27.21

    • NAID

      130008137914

    • ISSN
      2186-6147, 2186-6155
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] BMA投与前の抜歯後における義歯治療に関連して発症したMRONJの探索的研究2022

    • Author(s)
      今待賢治、秦浩信、吉川和人、和田麻友美、服部倫寛、江戸美奈子、北川善政
    • Organizer
      第67回日本口腔外科学会総会・学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Post-Extraction Adverse Events In Patients On Bevacizumab: A Single Center Study2021

    • Author(s)
      Kenji Imamachi, Hironobu Hata, Kazuhito Yoshikawa, Kitagawa Yoshimasa
    • Organizer
      MASCC/ISOO Annual Meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] がん治療に関連した口腔カンジダ症の臨床的検討2021

    • Author(s)
      今待賢治、秦浩信、北川善政
    • Organizer
      第34回日本口腔診断学会・第31回日本口腔内科学会合同学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] ベバシズマブによって生じたMRONJの3例2021

    • Author(s)
      今待賢治、秦浩信、江戸美奈子、栗林和代、新山宗、林信、上田倫弘、北川善政
    • Organizer
      第66回日本口腔外科学会総会・学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Post-Extraction Adverse Events In Patients On Bevacizumab: A Single Center Study2021

    • Author(s)
      Kenji Imamachi, Hironobu Hata, Kazuhito Yoshikawa, Yoshimasa Kitagawa
    • Organizer
      MASCC/ISOO annual meeting 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血管新生阻害薬によるMRONJの2例2020

    • Author(s)
      今待賢治, 國井信彦, 江戸美奈子, 圖司陽子 宮本亜有美, 諸橋悠希, 秦浩信
    • Organizer
      第6回日本がん口腔支持療法学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Post-extraction adverse events in patients on bevacizumab: a single center study2020

    • Author(s)
      Kenji Imamachi, Hironobu Hata, Kazuhito Yoshikawa, Yoshimasa Kitagawa
    • Organizer
      MASCC/ISOO 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院におけるベバシズマブ使用患者の抜歯に関する調査2019

    • Author(s)
      今待賢治, 國井信彦, 新山 崇, 林 信, 上田倫弘, 秦 浩信, 北川 善政
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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