Efficacy and safety of dose-dense chemotherapy for early-stage breast cancer under prophylactic pegfilgrastim administration: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022

Takamichi Yokoe¹, Tetsuhiro Yoshinami², Kazuki Nozawa³, Yukinori Ozaki⁴, Hiroshi Nishio⁵, Kenji Tsuchihashi⁶, Eiki Ichihara⁷, Yuji Miura⁸, Makoto Endo⁹, Shingo Yano¹⁰, Dai Maruyama¹¹, Nobuyuki Susumu¹², Munetaka Takekuma¹³, Takashi Motohashi¹⁴, Mamoru Ito⁶, Eishi Baba¹⁵, Nobuaki Ochi¹⁶, Toshio Kubo¹⁷, Keita Uchino¹⁸, Takahiro Kimura¹⁹, Yutaro Kamiyama²⁰, Shinji Nakao²¹, Shinobu Tamura²², Hitomi Nishimoto²³, Yasuhisa Kato²⁴, Atsushi Sato²⁵, Toshimi Takano⁴

Affiliations

¹ Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 161-0016, Japan. takamichi.yokoe@gmail.com.
² Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
³ Department of Advanced Clinical Research and Development, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan.
⁴ Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
⁵ Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
⁶ Department of Hematology, Oncology and Cardiovascular Medicine, Fukuoka, Japan.
⁷ Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
⁹ Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
¹⁰ Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
¹¹ Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
¹² Department of Obstetrics and Gynecology, International University of Health and Welfare Narita Hospital, Chiba, Japan.
¹³ Deparment of Gynecology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁴ Department of Obstetrics and Gynecology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
¹⁵ Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹⁶ Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
¹⁷ Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
¹⁸ Department of Medical Oncology, NTT Medical Center Tokyo, Tokyo, Japan.
¹⁹ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
²⁰ Department of Clinical Oncology/Hematology, The Jikei University School of Medicine, Tokyo, Japan.
²¹ Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan.
²² Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.
²³ Department of Nursing, Okayama University Hospital, Okayama, Japan.
²⁴ Department of Drug Information, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Kanagawa, Japan.
²⁵ Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Aomori, Japan.

PMID: 39934515
DOI: 10.1007/s10147-025-02716-2

Meta-Analysis

Efficacy and safety of dose-dense chemotherapy for early-stage breast cancer under prophylactic pegfilgrastim administration: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022

Takamichi Yokoe et al. Int J Clin Oncol. 2025 Apr.

. 2025 Apr;30(4):674-683.

doi: 10.1007/s10147-025-02716-2. Epub 2025 Feb 12.

Authors

Affiliations

¹ Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 161-0016, Japan. takamichi.yokoe@gmail.com.
² Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
³ Department of Advanced Clinical Research and Development, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan.
⁴ Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
⁵ Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
⁶ Department of Hematology, Oncology and Cardiovascular Medicine, Fukuoka, Japan.
⁷ Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
⁹ Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
¹⁰ Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
¹¹ Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
¹² Department of Obstetrics and Gynecology, International University of Health and Welfare Narita Hospital, Chiba, Japan.
¹³ Deparment of Gynecology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁴ Department of Obstetrics and Gynecology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
¹⁵ Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹⁶ Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
¹⁷ Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
¹⁸ Department of Medical Oncology, NTT Medical Center Tokyo, Tokyo, Japan.
¹⁹ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
²⁰ Department of Clinical Oncology/Hematology, The Jikei University School of Medicine, Tokyo, Japan.
²¹ Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan.
²² Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.
²³ Department of Nursing, Okayama University Hospital, Okayama, Japan.
²⁴ Department of Drug Information, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Kanagawa, Japan.
²⁵ Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Aomori, Japan.

PMID: 39934515
DOI: 10.1007/s10147-025-02716-2

Abstract

Background: In early-stage breast cancer, dose-dense chemotherapy, which involves the administration of standard doses at shorter intervals, is safer when administered with granulocyte colony-stimulating factor (G-CSF) to mitigate chemotherapy-induced neutropenia. This study aimed to thoroughly evaluate the advantages and disadvantages of dose-dense regimens based on the use of G-CSF.

Methods: A systematic review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing dose-dense chemotherapy with prophylactic pegfilgrastim administration in early-stage breast cancer were included. Outcomes included overall survival, event-free survival, incidence of febrile neutropenia, quality of life (QOL), and pain. Meta-analyses were performed on outcomes with sufficient data.

Results: Our literature search identified 23 RCTs. Overall survival and event-free survival showed a trend favoring dose-dense therapy (hazard ratio, 0.90, 0.90; 95% confidence interval [CI] 0.78 - 1.03, 0.80 - 1.01; p = 0.13; 0.07, respectively). The incidence of febrile neutropenia was similar between the groups (odds ratio, 0.90; 95% CI 0.58 - 1.40; p = 0.65). Mortality due to infection could not be compared owing to the small number of events. Pain increased with dose-dense therapy (odds ratio 2.57; 95% CI 1.00 - 6.62; p = 0.05), likely from G-CSF-induced bone pain. Only one study examined QOL, showing a decline with chemotherapy that recovered after treatment.

Conclusions: Dose-dense chemotherapy trended toward improved survival outcomes without increasing the risk of infection, although pain increased. Further research should identify the specific subgroups that most benefit from dose-dense regimens. More data are needed on the impact on QOL.

Keywords: Dose-dense chemotherapy; Early-stage breast cancer; Granulocyte colony-stimulating factor; Neutropenia; Prophylactic pegfilgrastim.

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Conflict of interest statement

Declarations. Conflicts of interest: TE.Y. received honoraria from Kyowa-Kirin, Pfizer, Chugai, Eli Lilly, MSD, AstraZeneca and Eisai. Y.O. received honoraria from Daiichi-Sankyo, Pfizer, Chugai, Lilly and Kyowa Kirin. K.T. received honoraria from Ono, Chugai, Taiho and Novartis. E.I. received honoraria from Eli Lilly, and research funding from MSD, Ono, Janssen Pharma and Takeda. Y.M. received honoraria from Ono, MSD, Takeda, Eisai and Bristol Myers Squibb, and research funding from MSD and Ono. S.Y. received research funding from Otsuka. D.M. received honoraria from Janssen, Nippon Shinyaku, Eisai, Mundipharma, Kyowa Kirin, Chugai, Zenyaku, MSD, SymBio, Sanofi, AbbVie, Takeda, Astra Zeneca and Bristol Myers Squibb, and research funding from Biopharma, Novartis, Kyowa Kirin, Ono, Chugai, Janssen, Takeda, Otsuka, Sanofi, Astellas, Bristol Myers Squibb, AbbVie, Eisai, MSD, Taiho and Astra Zeneca. T.M. received honoraria from Astra Zeneca, Chugai and Myriadgenetics. E.B. received honoraria from Chugai, and Daiichi-Sankyo, and research funding from Taiho and Chugai. T.KU. received honoraria from Chugai. T.KI. received honoraria from Sanofi. S.N. received honoraria from Kyowa Kirin. A.S. received honoraria and scholarship donation from Chugai and Taiho. T.T. received honoraria from Daiichi-Sankyo, Chugai and Eli Lilly. Other authors declare that there are no conflicts of interest associated with this manuscript. The other authors have no conflict of interest. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: All authors consented to the publication of this study.

References

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Efficacy and safety of dose-dense chemotherapy for early-stage breast cancer under prophylactic pegfilgrastim administration: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022

Affiliations

Efficacy and safety of dose-dense chemotherapy for early-stage breast cancer under prophylactic pegfilgrastim administration: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Medical