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Renin–angiotensin–aldosterone system inhibitors are associated with improved paclitaxel-induced peripheral neuropathy in lung cancer: a study using administrative claims data

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Abstract

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients’ quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin–angiotensin–aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN).

Methods

An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine–Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding.

Results

Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762–0.929). The result was consistent in various sensitivity analyses and important subgroup analyses.

Conclusions

RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer.

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Data availability

The study data can be purchased from Medical Data Vision (Tokyo, Japan; https://www.mdv.co.jp/).

Code availability

Not applicable.

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Acknowledgements

We would like to thank ZENIS for English language editing.

Funding

Departmental funding from the Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine.

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Authors and Affiliations

  1. Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-Machi, Abeno-Ku, Osaka, 545-8585, Japan

    Yasutaka Ihara, Takumi Imai, Tetsuya Kimura, Miho Otani, Ryota Kawai & Ayumi Shintani

  2. Department of Clinical Oncology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan

    Kenji Sawa

  3. Primary Medical Science Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Tetsuya Kimura

  4. Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan

    Shingo Takatori

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  1. Yasutaka Ihara
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Contributions

Conceptualization: Yasutaka Ihara, Kenji Sawa, Takumi Imai, Tetsuya Kimura, Miho Otani, Shingo Takatori, and Ayumi Shintani; data curation: Yasutaka Ihara, Kenji Sawa, and Ryota Kawai; formal analysis: Yasutaka Ihara and Ryota Kawai; funding acquisition: Ayumi Shintani; investigation: Yasutaka Ihara; methodology: Yasutaka Ihara, Takumi Imai, and Ayumi Shintani; project administration: Yasutaka Ihara; resources: Ayumi Shintani; software: Ayumi Shintani; supervision: Yasutaka Ihara and Ayumi Shintani; validation: Yasutaka Ihara and Ryota Kawai; visualization: Yasutaka Ihara; writing – original draft: Yasutaka Ihara, Kenji Sawa, and Takumi Imai; writing – review and editing: Yasutaka Ihara, Kenji Sawa, Takumi Imai, Tetsuya Kimura, Miho Otani, Ryota Kawai, Shingo Takatori, and Ayumi Shintani.

Corresponding author

Correspondence to Yasutaka Ihara.

Ethics declarations

Ethics approval

The Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects are not applied to clinical studies that use only anonymized data. The data used in this study were anonymized by the MDV. Therefore, informed consent was waived.

Competing interests

Author Yasutaka Ihara, Miho Otani, Ryota Kawai, and Shingo Takatori declare they have no financial interests. Kenji Sawa received lecture fees in the past 36 months from Eli Lilly Japan, AstraZeneca, Ono Pharmaceutical, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, and Kyowa Kirin. Takumi Imai received lecture fees in the past 36 months from JCR Pharmaceuticals and Kyowa Kirin. TK is an employee of Daiichi Sankyo, which owns the patent for and manufactures one of the study drugs (olmesartan). Tetsuya Kimura was involved only in the study design and discussion of the results and played no role in data processing or conducting the analyses. Ayumi Shintani received lecture fees in the past 36 months from AbbVie, AstraZeneca plc, Asahi Kasei Corporation, Astellas Pharma, Bayer Yakuhin, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Janssen Pharmaceutical, Kissei Pharmaceutical, Kyowa Kirin, Mallinckrodt Pharmaceuticals, Maruho, Merck Biopharma, Mitsubishi Tanabe Pharma Corporation, Nipro Corporation, Nippon Shinyaku, Novo Nordisk Pharma, Ono Pharmaceutical, Pfizer, Shionogi Pharma, Taisho Pharmaceutical, Takeda Pharmaceutical Company Limited, and Torii Pharmaceutical.

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Ihara, Y., Sawa, K., Imai, T. et al. Renin–angiotensin–aldosterone system inhibitors are associated with improved paclitaxel-induced peripheral neuropathy in lung cancer: a study using administrative claims data. Support Care Cancer 31, 730 (2023). https://doi.org/10.1007/s00520-023-08193-5

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