diurnal variation of cisplatin-induced anti-tumor effect and renal toxicity

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15328
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Gihu University of Medical Science
• Principal Investigator: YOSHIOKA HIROKI 岐阜医療科学大学, 薬学部, 講師 (30756606)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 時間薬理 / 時間毒性 / シスプラチン

Outline of Final Research Achievements

Cisplatin-induced diurnal renal toxicity and chrono-pharmacology of anti-cancer reagent was already reported. However, there is no report evaluating chrono-toxicity and chrono-pharmacological effect by cisplatin at same time. In the present study, I investigated diurnal variation of cisplatin-induced anti-tumor effect and renal toxicity using Nude mice. I injected cisplatin 3 times for 4 weeks at ZT2 (8:00) or ZT14 (20:00). I demonstrated that cisplatin-induced renal toxicity, body weight reduction and anti-cancer effect were observed both at ZT2 (8:00) and ZT14 (20:00), respectively. Moreover, we showed that these effect at ZT14 (20:00) was observed stronger than that of ZT2 (8:00). My present result may be contributed to reduce medical bills by modulating cisplatin injection time.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

シスプラチンは白金を含有する悪性腫瘍に対する化学療法剤であり、多くのがん化学療法プロトコールにおいて中心的な役割を果たしているが、20-30%の患者で急性腎障害等の副作用が認めれる。薬理作用と毒性作用が異なる時刻であれば、患者のQOL向上に強く貢献できるものになるが、今回の結果では薬理作用及び毒性作用の強く顕れる時刻は一致していた。
近年、医療費高騰の問題もあることから、シスプラチンの作用が強く出る時刻に投与すれば、医療費削減に貢献できる可能性を秘めている。