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Prediction Model for Severe Thrombocytopenia Induced by Gemcitabine Plus Cisplatin Combination Therapy in Patients with Urothelial Cancer

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Abstract

Background

Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion.

Objective

A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning.

Methods

We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia.

Results

Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58).

Conclusions

Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.

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Acknowledgements

The authors would like to thank Editage (https://www.editage.com/) for editing and reviewing this manuscript for English language.

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Author notes

  1. Noriaki Matsumoto and Tomohiro Mizuno contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Noriaki Matsumoto, Tomohiro Mizuno, Yosuke Ando, Koki Kato, Tsuyoshi Nakai & Shigeki Yamada

  2. Sugi Pharmacy Co., Ltd, Obu, Aichi, Japan

    Noriaki Matsumoto

  3. Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Masanori Nakanishi

  4. Department of Pharmacy Practice and Science, The University of Arizona R. Ken Coit College of Pharmacy, Tucson, AZ, USA

    Jeannie K. Lee

  5. Department of Information Engineering, Meijo University, Nagoya, Japan

    Yoshitaka Kameya

  6. Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Wataru Nakamura, Kiyoshi Takahara & Ryoichi Shiroki

Authors
  1. Noriaki Matsumoto
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  2. Tomohiro Mizuno
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  3. Yosuke Ando
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  6. Tsuyoshi Nakai
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  8. Yoshitaka Kameya
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Corresponding author

Correspondence to Tomohiro Mizuno.

Ethics declarations

Conflict of interest

Shigeki Yamada has received honoraria from Nippon Shinyaku Co., Ltd, Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd. Tomohiro Mizuno is an editorial board member of Clinical Drug Investigation. Noriaki Matsumoto, Yosuke Ando, Koki Kato, Masanori Nakanishi, Tsuyoshi Nakai, Jeannie K. Lee, Yoshitaka Kameya, Wataru Nakamura, Kiyoshi Takahara, and Ryoichi Shiroki declare no conflicts of interest regarding the subject of this study.

Ethics approval

This study was approved by the Ethics Board of Fujita Health University Hospital (Ethics Committee approval number: HM23-027; date of approval 9 May 2023) and was conducted in accordance with the appropriate guidelines.

Consent for publication

Not applicable.

Consent to participants

An opt-out approach was used to obtain informed consent according to the guidelines of the Fujita Health University Hospital Ethics Board.

Code availability

Not applicable.

Author contributions

NM contributed to the study conception and design and drafted the manuscript. NM, KK, MN, and TN analyzed and interpreted the data. YA, JKL, YK, WN, KT, RS, and SY contributed to the study design and reviewed the manuscript. TM contributed to the study conception and design, drafted the manuscript, and supervised the execution of the study.

Data availability statement

Data archiving is not mandated but data will be made available on reasonable request.

Funding

This work was supported by the JSPS KAKENHI (grant number 21K06696) and the Research Center for Pathogenesis of Intractable Diseases, Research Institute of Meijo University, Japan.

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Matsumoto, N., Mizuno, T., Ando, Y. et al. Prediction Model for Severe Thrombocytopenia Induced by Gemcitabine Plus Cisplatin Combination Therapy in Patients with Urothelial Cancer. Clin Drug Investig 44, 357–366 (2024). https://doi.org/10.1007/s40261-024-01361-3

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  • DOI: https://doi.org/10.1007/s40261-024-01361-3

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