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Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival

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Abstract

Purpose This multicenter phase II study examined the impact of pathological effect on survival after preoperative chemotherapy in Japanese women with early stage breast cancer. Patients and methods Prior to surgery, patients received four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 q3w) followed by four cycles of docetaxel (75 mg/m2 q3w). Primary endpoint was 3 year disease free survival (DFS) stratified by the absence or presence of Quasi-pCR (QpCR; absence of invasive tumor or only focal residual tumor cells). Secondary endpoints were predictors for QpCR, clinical response, breast conservation rate, and safety. Results Between June 2002 and June 2004, 202 women were enrolled. Among 191 assessable patients, 25% achieved QpCR. With 40 months median follow-up, 3 year DFS was estimated at 91% for all patients. 3 year DFS for patients with QpCR was 98% vs. 89% without QpCR (hazard ratio 0.38 [95% Confidence Interval 0.09–0.84], P = 0.0134). HER2 status and response to FEC were independent predictors of QpCR. The overall clinical response was 75%; 85% of patients achieved breast conservation. Grade 3/4 neutropenia was the most common adverse event, observed in 44% and 35% of patients during FEC and docetaxel, respectively. Treatment related side effects were manageable; there were no treatment related fatalities. Conclusion FEC followed by docetaxel is an active and manageable preoperative regimen for women with early stage breast cancer. QpCR following preoperative chemotherapy predicts favorable DFS. HER2 overexpression and clinical response to FEC predict QpCR.

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Acknowledgments

We wish to thank the patients who participated in the JBCRG 01 clinical trial. We also thank Drs. Shunichi Inamoto, Tadashi Kobayashi, and Taketo Mukaiyama for their helpful advice as the members of efficacy and safety evaluating committee. We are also grateful to sanofi-aventis, Dr. Steven Olsen, Dr. Takashi Shimamoto, Arika Yoshida, Tomoko Kawamoto, Takeshi Mera and Daisuke Nozaki, for their scientific advice. This study was sponsored by Osaka Cancer Research Foundation and Advanced Clinical Research Organization.

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Authors and Affiliations

  1. Department of Surgery (Breast Surgery), Graduate School of Faculty of Medicine, Kyoto University, 54 Shogoin-Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masakazu Toi

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

    Seigo Nakamura

  3. Division of Clinical Trials and Research and Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

    Katsumasa Kuroi

  4. Department of Breast Oncology, Aichi Cancer Center Hospital, Aichi, Japan

    Hiroji Iwata

  5. Division of Breast Oncology, National Kyushu Cancer Center, Fukuoka, Japan

    Shinji Ohno

  6. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Norikazu Masuda

  7. Shinjyuku Breast Center Kusama Clinic, Tokyo, Japan

    Mikihiro Kusama

  8. Sapporo Kotoni Breast Clinic, Hokkaido, Japan

    Kosuke Yamazaki

  9. Department of Surgery, Hiroshima City Asa Hospital, Hiroshima, Japan

    Kazuhumi Hisamatsu

  10. Department of Breast and Endocrine Surgery, Nagoya Medical Center, Nagoya National Hospital, Aichi, Japan

    Yasuyuki Sato

  11. Department of Surgery, Iwate Medical University, Iwate, Japan

    Masahiro Kashiwaba

  12. Department of Breast Oncology, Tokyo Medical University Hospital, Tokyo, Japan

    Hiroshi Kaise

  13. Department of Pathology, Saitama Cancer Center, Saitama, Japan

    Masafumi Kurosumi

  14. Department of Basic Pathology, National Defense Medical College, Saitama, Japan

    Hitoshi Tsuda

  15. Department of Breast Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan

    Futoshi Akiyama

  16. Department of Biostatistics/Epidemiology and Preventive Health Science, School of Health Science and Nursing, University of Tokyo, Tokyo, Japan

    Yasuo Ohashi

  17. Department of Breast Surgery, Kansai Rosai Hospital, Hyogo, Japan

    Yuichi Takatsuka

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  1. Masakazu Toi
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Correspondence to Masakazu Toi.

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Toi, M., Nakamura, S., Kuroi, K. et al. Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival. Breast Cancer Res Treat 110, 531–539 (2008). https://doi.org/10.1007/s10549-007-9744-z

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  • DOI: https://doi.org/10.1007/s10549-007-9744-z

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