2023 Fiscal Year Final Research Report
Investigation of anti-cancer effect of anti-EGFR antibody based on quantitative evaluation of its pharmacokinetics and glycosylation in cancer patients
| Project/Area Number |
20K16040
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Shinshu University (2022-2023)
Hamamatsu University School of Medicine (2020-2021) |
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Principal Investigator |
Shibata Kaito 信州大学, 医学部附属病院, 薬剤主任 (00857055)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | がん化学療法 / 抗EGFR抗体薬 / 薬物動態 / 臨床効果 / がん悪液質 / 炎症性サイトカイン / 糖鎖修飾 / セツキシマブ |
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| Outline of Final Research Achievements |
Cancer patients have a large variation in anti-cancer and adverse effects of anti-EGFR antibody drugs. The variation is partially associated with individual pharmacokinetics. In addition, the cancer progression and glycosylation of the antibody structure are potentially responsible for clinical responses to anti-EGFR antibody drugs. This study focused on the pathology of cancer cachexia and clarified the factors of individual variability in the pharmacokinetics and clinical symptoms of cetuximab in head and neck cancer patients. Although it is still in the development stage, this study developed a method for determining the carbohydrate structure of serum cetuximab. The progressive cancer cachexia and its related alteration of serum proinflammatory cytokine and albumin were associated with the decrease of serum cetuximab. The elevated systemic inflammation in cachectic cancer patients led to severe fatigue under cetuximab treatment, regardless of its pharmacokinetics.
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| Free Research Field |
医療薬学、臨床薬理学、薬物動態学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、進行がん患者における抗EGFR抗体薬の体内動態や臨床効果の個人差を規定する要因が一部明らかとなった。この研究成果の学術的意義として、がん悪液質の進行度やがん進行に伴う全身性の炎症度を評価することで、抗EGFR抗体薬の体内動態や身体症状の予測が可能となる。本研究成果の社会的意義として、がん患者における抗EGFR抗体薬の体内動態や臨床症状の予測は、その忍容性を向上させるとともに、がん化学療法における抗体薬の薬物治療管理の質向上が期待できる。
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