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Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression

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Abstract

Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response (pCR) rates. We evaluated the efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2-negative breast cancer were randomly assigned to preoperatively receive CP-CEF (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and wPTX [80 mg/m2, day 1, 8, 15] followed by four 3-week cycles of CEF [500/100/500 mg/m2] or P-CEF (four cycles of wPTX followed by four cycles of CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6 %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2 (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity.

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Acknowledgments

We thank the women who participated in this trial; Hitoshi Tsuda, Futoshi Akiyama, and Shinobu Masuda for central review of pathological diagnoses; Hiroi Kasai for preparing for this study; and Midori Tanaka for writing the study report. This study had been performed as a registration-directed trial in accordance with the Good Clinical Practice guideline [Enforcement Regulation No. 24 of the MHLW (revised GCP) dated on February 29, 2008], which is published by the revised Pharmaceutical Affairs Act in Japan (No. 84 dated on June 21, 2006). This study was supported by the Health and Labour Sciences Research Grants (Clinical Cancer Research), Ministry of Health, Labour and Welfare (Grant Number: MHLW, 2009 Clinical Cancer Research General-020) and the Cancer Research and Development grants, and National Cancer Center (Grant Number: 2011-A-42).

Conflicts of interest

MA has declared conflicts related to lecture fees form Kyowa Hakko Kirin Co., Ltd. SO has declared conflicts related to lecture fees from Astra Zeneca K. K., Novartis Pharma K. K., and Chugai Pharmaceutical Co., Ltd. YF has declared conflicts related to conducting research sponsored by Kyowa Hakko Kirin Co., Ltd., Glaxo Smith Kline K. K., Sanofi-Aventis K. K., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Bio Development Center Limited, Chugai Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K. K., Pfizer Japan Inc., Janssen Pharmaceutical K. K., and Kissei Pharmaceutical Co., Ltd., and remunerations from Astra Zeneca K. K., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Glaxo Smith Kline K. K., Sanofi-Aventis K. K., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., Nippon Kayaku Co., Ltd., Novartis Pharma K. K., and Bristol-Myers Squibb K. K. All remaining authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Masashi Ando

  2. Department of Breast Surgical Oncology, St. Luke’s International Hospital, Tokyo, Japan

    Hideko Yamauchi

  3. Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan

    Kenjiro Aogi

  4. Department of Breast Oncology and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan

    Satoru Shimizu

  5. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

    Hiroji Iwata

  6. Department of Surgery and Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Norikazu Masuda

  7. Division of Breast Surgery, Chiba Cancer Center, Chiba, Japan

    Naohito Yamamoto

  8. Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan

    Kenichi Inoue

  9. Department of Clinical Oncology, National Kyushu Cancer Center, Fukuoka, Japan

    Shinji Ohono

  10. Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

    Katsumasa Kuroi

  11. Clinical Trial Coordinating Center, Kitasato Academic Research Organization, Kitasato University, Tokyo, Japan

    Tetsutaro Hamano

  12. Exploratory Oncology Research & Clinical Trial Center, Chiba, Japan

    Tamie Sukigara

  13. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

    Yasuhiro Fujiwara

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  1. Masashi Ando
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  2. Hideko Yamauchi
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  13. Yasuhiro Fujiwara
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Correspondence to Masashi Ando.

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Ando, M., Yamauchi, H., Aogi, K. et al. Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression. Breast Cancer Res Treat 145, 401–409 (2014). https://doi.org/10.1007/s10549-014-2947-1

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  • DOI: https://doi.org/10.1007/s10549-014-2947-1

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