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A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer

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Abstract

Purpose

Better treatments for triple-negative breast cancer (TNBC) are needed. To address this need, we studied the effects of preoperative metronomic paclitaxel/cyclophosphamide/capecitabine (mPCX) followed by 5-fluorouracil (FU)/epirubicin/cyclophosphamide (FEC) as preoperative chemotherapy in TNBC patients.

Methods

Forty primary TNBC patients received four cycles of metronomic paclitaxel (80 mg/m2 on Days 1, 8, and 15), cyclophosphamide (50 mg/body daily), and capecitabine (1,200 mg/m2 daily), followed by four cycles of 5-FU (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. The primary end point was the pathological complete response (pCR) rate.

Results

Forty patients formed the intent-to-treat population. The median dose intensities of paclitaxel, cyclophosphamide, and capecitabine were 89.7, 92.1, and 89.8 %, respectively. Five patients discontinued mPCX and two discontinued FEC, primarily because of adverse events, resulting in a per-protocol population (PPS) of 33 patients. The pCR (ypT0/Tis ypN0) rate was 47.5 % (19/40) in the intent-to-treat population and 54.5 % (18/33) in the PPS. The clinical response rates were 36/40 (90.0 %) and 31/33 (93.9 %) in the intent-to-treat and PPS, respectively. The breast conservation rate was 72.7 % (24/33), and 5/13 patients underwent partial resection instead of pre-planned total mastectomy. Grade 3–4 adverse events included neutropenia (35 %), leukopenia (25 %), and hand-foot syndrome (8 %).

Conclusions

Metronomic PCX followed by FEC chemotherapy was associated with a high pCR rate and low toxicity in TNBC patients. Further studies of this regimen in larger numbers of patients are warranted.

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Acknowledgments

The present study was funded by the Japan Breast Cancer Research Group. We thank Marion Barnett and Daniel McGowan, PhD, for providing editorial support. The authors would also like to gratefully acknowledge the support of the patients and staff at each institute, management office, and data center.

Conflict of interest

Norikazu Masuda has received honoraria from Chugai. Satoshi Morita has received honoraria and research funding from Chugai. Masakazu Toi has received honoraria from Chugai and research funding from Chugai and BMS. All other authors have no conflicts of interest to declare.

Ethical standard

The experiments performed in this study comply with current Japanese law.

Author information

Authors and Affiliations

  1. Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan

    N. Masuda & M. Mizutani

  2. Hiroshima City Hospital, Hiroshima, Japan

    K. Higaki & S. Ohtani

  3. Toranomon Hospital, Tokyo, Japan

    T. Takano

  4. Osaka Rousai Hospital, Osaka, Japan

    N. Matsunami

  5. Yao Municipal Hospital, Osaka, Japan

    T. Morimoto

  6. Gunma Prefectural Cancer Center, Ota, Japan

    T. Miyamoto

  7. Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    K. Kuroi

  8. Clinical Research Center, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    S. Ohno

  9. Yokohama City University Medical Center, Kanagawa, Japan

    S. Morita

  10. Graduate School of Medicine Kyoto University, Kyoto, Japan

    M. Toi

Authors
  1. N. Masuda
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  2. K. Higaki
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  10. S. Ohno
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Corresponding author

Correspondence to N. Masuda.

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Masuda, N., Higaki, K., Takano, T. et al. A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer. Cancer Chemother Pharmacol 74, 229–238 (2014). https://doi.org/10.1007/s00280-014-2492-y

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