Drug repositioning to avoid adverse events associated with colorectal cancer chemotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kyushu University
• Principal Investigator: Kawashiri Takehiro 九州大学, 薬学研究院, 講師 (30621685)
• Co-Investigator(Kenkyū-buntansha): 小林 大介 九州大学, 薬学研究院, 講師 (00403973)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: がん化学療法 / 有害事象 / 末梢神経障害 / 手足症候群 / ドラッグ・リポジショニング / プロトンポンプ阻害薬 / 支持療法 / オキサリプラチン

Outline of Final Research Achievements

Sufficient supportive care has not been established for peripheral neuropathy and hand-foot syndrome, which are adverse events of colorectal cancer chemotherapy. The purpose of this research project was to search for useful therapeutic or prophylactic agents for these symptoms through basic research, database analysis, and clinical retrospective studies.
In basic research, it was found that Sokeikakketsuto, amino acids cystine and theanine, and proton pump inhibitors have efficacy against oxaliplatin-induced peripheral neuropathy, and proton pump inhibitors also have efficacy against capecitabine-induced hand-foot syndrome, respectively.
Furthermore, proton pump inhibitors were consistently associated with fewer reports of peripheral neuropathy in adverse drug event database analyses and clinical retrospective studies.

Free Research Field

医療薬学、臨床薬学

Academic Significance and Societal Importance of the Research Achievements

大腸がん化学療法の有害事象である末梢神経障害・手足症候群は患者の心身的負担になるばかりか、治療の継続を困難とさせるものでもあり、対応策の確立が強く求められている。本研究課題の中で、これらの有害事象に有効な薬剤が基礎研究で複数明らかとなり、さらにプロトンポンプ阻害薬の末梢神経障害抑制効果については大規模医療情報データベース解析や臨床研究においても一貫して確認がされた。本研究結果をもとにさらに臨床的エビデンスを構築できれば、これらの有害事象によりがん治療を断念する患者の割合が低下すること、さらには結果的にがん治療の奏効率の上昇に繋がることが期待できる。