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Neoadjuvant sequential epirubicin and docetaxel followed by surgery-radiotherapy and post-operative docetaxel or gemcitabine/vinorelbine combination based on primary response: a multimodality approach for locally advanced breast cancer

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Abstract

Background

Locally advanced breast cancer (LABC) remains a major clinical issue despite progress achieved in recent years. Herein, we present the mature results of a multimodality treatment program tailoring epirubicin (EPI), docetaxel (DOC) and gemcitabine–vinorelbine (GEV) peri-operatively in LABC.

Patients and methods

Stage III, Eastern Cooperative Oncology Group-Performance status ≤2 patients were eligible. A biopsy documentation had to be performed before the start of chemotherapy (CT). Treatment consisted of four EPI (100 mg/m2, d1q2w) followed by three DOC (100 mg/m2, d1q3w); surgery 3–4 weeks from CT completion, followed by radiation therapy (RT) and CT according to response; partial or complete (PR/CR):DOC, no change or progressive disease (NC/PD):GEV. Primary endpoints were: (a) response and conversion to operability/conservative surgery and (b) overall survival (OS) and time to recurrence (TTR).

Results

Fifty-six women, aged 32–75 (median 52 years), 24 IIIA and 32 IIIB were enrolled; 53 patients completed the entire program. Toxicity was acceptable and no treatment-related death was observed. Efficacy: clinical response rate (RR) 71.4% (40 patients); clinical complete response rate 33.9% (19 patients). Pathological response rate (RR) 67.8% (38 patients); pathological complete response rate 21.4% (12 patients). 33 (58.9%) and 19 (33.9%) patients, respectively, had radical and conservative operations without increased morbidity. After a median follow-up of 62 months, median OS has not yet been reached, while median TTR was 42 months. OS was longer in patients with clinical (p = 0.004) and pathological response (p = 0.002), RT (p < 0.0001) and post-operative DOC (p = 0.038). TTR was favorably affected by pR (p < 0.0001), RT (p < 0.0004) and post-operative DOC (p = 0.005). Pre-operative CT seemed to be equally active throughout all subgroups according to histology, ER/PR and HER2 status.

Conclusion

The treatment program of the present study allowed for the completion of an effective therapy at the cost of acceptable toxicity. The results of this study suggest a central role of CT for LABC and the value of eventually dose-dense, EPI- and DOC-based CT in a large proportion of LABC patients, regardless of biological tumor profile. Furthermore, tumor response (cR, pR) is an important surrogate for patients survival and further therapy management.

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Abbreviations

CR:

Complete response

cR:

Clinical response

DFS:

Disease free survival

DOC:

Docetaxel

ECG:

Electrocardiogram

ECOG:

Eastern Cooperative Oncology Group

EPI:

Epirubicin

FNA:

Fine needle aspiration

GEPARDUO:

German Preoperative Adriamycin Docetaxel Study Group

GEV:

Gemcitabine–vinorelbine

IBC:

Inflammatory breast cancer

IV:

Intravenously

LABC:

Locally advanced breast cancer

LVEF:

Left ventricular ejection fraction

MUGA:

Multigated acquisition scan

NSABP:

National Surgical Adjuvant Breast and Bowel Project

NC:

No change

OS:

Overall survival

PD:

Progressive disease

PR:

Partial response

pR:

Pathologic response

PS:

Performance status

PST:

Primary systemic therapy

RECIST:

Response evaluation criteria in solid tumors

RR:

Response rate

TTR:

Time to recurrence

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Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. First Department of Medical Oncology, “St. Savas” Anticancer Hospital, 171 Alexandras’ Avenue, 11522, Athens, Greece

    Panteleimon Kountourakis, Dimitrios Doufexis, Savoula Maliou & Alexandros Ardavanis

  2. Fourth Department of Surgery, “St. Savas” Anticancer Hospital, Athens, Greece

    Ioannis Missitzis & Vassileios Zobolas

  3. Second Department of Radiation Oncology, “St. Savas” Anticancer Hospital, Athens, Greece

    Georgios Pissakas & Anastasia Sotiropoulou

  4. Department of Surgical Pathology, “St. Savas” Anticancer Hospital, Athens, Greece

    Niki Arnogiannaki

Authors
  1. Panteleimon Kountourakis
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  2. Ioannis Missitzis
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  3. Dimitrios Doufexis
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  4. Vassileios Zobolas
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  5. Georgios Pissakas
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  6. Niki Arnogiannaki
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  7. Savoula Maliou
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  8. Anastasia Sotiropoulou
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  9. Alexandros Ardavanis
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Correspondence to Alexandros Ardavanis.

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Kountourakis, P., Missitzis, I., Doufexis, D. et al. Neoadjuvant sequential epirubicin and docetaxel followed by surgery-radiotherapy and post-operative docetaxel or gemcitabine/vinorelbine combination based on primary response: a multimodality approach for locally advanced breast cancer. J Cancer Res Clin Oncol 137, 221–228 (2011). https://doi.org/10.1007/s00432-010-0878-8

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  • DOI: https://doi.org/10.1007/s00432-010-0878-8

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