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Chemotherapy-induced neutropenia as a prognostic factor in patients with extensive-stage small cell lung cancer

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Abstract

Purpose

Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ES-SCLC).

Methods

The medical records from 214 patients with ES-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4, and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using the COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP group and 47 patients in the EP group.

Results

No significant difference was found between grades 0–3 and grade 4 neutropenia and overall survival (OS) in the EP group (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grades 0–3 and 633 days for grade 4 neutropenia, which was significantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identified as a significant predictor of longer OS (hazard ratio [HR], 0.50; 95% confidence interval (CI), 0.28–0.87, P = 0.015).

Conclusion

The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.

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Availability of data and material

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported in part by the University of Shizuoka academic research grant. The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Takehiro Miyagi, Daiki Tsuji & Kunihiko Itoh

  2. Faculty of Nursing, Japanese Red Cross College of Nursing, Tokyo, Japan

    Yohei Kawasakai

  3. Department of Pharmacy, Shizuoka Cancer Center, Shizuoka, Japan

    Hiroshi Ishikawa & Rei Tanaka

  4. Department of Pharmacy, Osaka City General Hospital, Osaka, Japan

    Masahiko Nakao

  5. Department of Pharmacy, Shizuoka General Hospital, Shizuoka, Japan

    Shigeru Nakagaki

  6. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

    Toshinobu Hayashi

  7. Department of Pharmacy, Tokyo Medical University Hospital, Tokyo, Japan

    Hideaki Ayuhara

  8. Department of Pharmacy, Kanagawa Cancer Center, Kanagawa, Japan

    Tomohiko Harada

  9. Department of Pharmacy, KKR Sapporo Medical Center, Hokkaido, Japan

    Shinya Tamaki

  10. Department of Pharmacy, Aichi Cancer Center Hospital, Aichi, Japan

    Akimitsu Maeda

  11. Department of Pharmacy, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

    Yasukata Ohashi

  12. Department of Pharmacy, Tochigi Cancer Center, Tochigi, Japan

    Yuichiro Arakawa

  13. Division of Pharmacy, Gunma Prefectural Cancer Center, Gunma, Japan

    Yukiyoshi Fujita

  14. Department of Pharmacy, Seirei Hamamatsu General Hospital, Shizuoka, Japan

    Keisuke Yamamoto

  15. Department of Pharmacy, Hamamatsu Medical Center, Shizuoka, Japan

    Yasunori Miyamoto

  16. Department of Pharmacy, Sumitomo Besshi Hospital, Ehime, Japan

    Takuya Yano

Authors
  1. Takehiro Miyagi
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  2. Daiki Tsuji
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  4. Hiroshi Ishikawa
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Contributions

Conception and design were performed by DT, TM, YK, and KY. Acquisition of data was carried out by HI, RT, MN, SN, THay, HA, THar, ST, AM, YO, YA, YF, KY, YM, and TY. Statistical analysis and interpretation of the data were carried out by TM, DT, and YK. Drafting of the article was carried out by DT, TM, and KI. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Daiki Tsuji.

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Ethical approval

The study protocol was approved by the ethics committee of each participating institution and conducted in accordance with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards and with the Ethical Guidelines for Medical and Health Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare, Japan.

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As this was a retrospective study, written informed consent to participate was not obtained. Instead, we offered the patients the right to opt out.

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The authors declare no competing interests.

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Miyagi, T., Tsuji, D., Kawasakai, Y. et al. Chemotherapy-induced neutropenia as a prognostic factor in patients with extensive-stage small cell lung cancer. Eur J Clin Pharmacol 79, 407–414 (2023). https://doi.org/10.1007/s00228-023-03451-1

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