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Coadministration of cytotoxic chemotherapeutic agents with irinotecan is a risk factor for irinotecan-induced cholinergic syndrome in Japanese patients with cancer

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Abstract

Background

Cholinergic syndrome is an acute adverse event frequently observed in patients administered irinotecan, and can sometimes negatively affect their quality of life. In some manifestations of the syndrome such as bradycardia, careful monitoring of patients is advised. In this study, we retrospectively investigated the risk factors associated with irinotecan-induced cholinergic syndrome in Japanese patients with cancer.

Methods

Patients who received irinotecan-based chemotherapy between April 2014 and June 2018 were examined. Patient backgrounds and clinical data during the first cycle of an irinotecan-containing regimen, including cholinergic syndrome manifestation within 24 h after the start of treatment, were collected from medical records. Univariate and multivariate analyses were performed to assess the risk of irinotecan-induced cholinergic syndrome.

Results

Among 179 patients administered an irinotecan-containing regimen, 51 experienced cholinergic syndrome after the initiation of treatment. The most common symptom was sweating followed by diarrhea, abdominal pain, lacrimation, and nasal discharge. 42 patients developed symptoms of cholinergic syndrome during their first treatment with irinotecan. Multivariate analyses revealed that the incidences of cholinergic syndrome in patients administered 2 or 3 chemotherapeutic agents; i.e., irinotecan plus 1 or 2 other cytotoxic anticancer drug(s), were significantly higher than that in patients administered irinotecan alone [odds ratio (OR) 4.35, 95% confidence interval (CI) 1.5–12, p = 0.0053 and OR 4.50, 95% CI 1.5–14, p = 0.0093, respectively]. The addition of a molecularly targeted drug did not affect the incidence of cholinergic syndrome.

Conclusion

The incidence rate of irinotecan-induced cholinergic syndrome increased concomitantly with the addition of cytotoxic chemotherapeutic agents administered.

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Acknowledgements

The authors would like to thank all the staff members of Showa University Hospital who cooperated in this study.

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Authors and Affiliations

  1. Division of Community Healthcare and Pharmacy, Department of Healthcare and Regulatory Sciences, Showa University School of Pharmacy, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Ayako Tsuboya, Iori Taki-Takemoto, Daisuke Kamei & Shinichi Iwai

  2. Department of Pharmacy, Kawasaki Municipal Tama Hospital, 1-30-37, Shukugawara, Tama-ku, Kawasaki, Kanagawa, 214-8525, Japan

    Ayako Tsuboya

  3. Institute of Molecular Oncology, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Ken-ichi Fujita & Yasutsuna Sasaki

  4. Division of Medical Oncology, Department of medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Yutaro Kubota, Hiroo Ishida & Yasutsuna Sasaki

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  1. Ayako Tsuboya
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  2. Ken-ichi Fujita
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Corresponding author

Correspondence to Ken-ichi Fujita.

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Tsuboya, A., Fujita, Ki., Kubota, Y. et al. Coadministration of cytotoxic chemotherapeutic agents with irinotecan is a risk factor for irinotecan-induced cholinergic syndrome in Japanese patients with cancer. Int J Clin Oncol 24, 222–230 (2019). https://doi.org/10.1007/s10147-018-1347-7

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  • DOI: https://doi.org/10.1007/s10147-018-1347-7

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