Skip to main content
SpringerLink
Log in

Neoadjuvant Treatment with Paclitaxel and Epirubicin in Invasive Breast Cancer

A Phase II Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and objectives: The modern management of locally advanced breast cancer includes a multimodal approach consisting of neoadjuvant chemotherapy (usually given as initial treatment), surgery, radiotherapy and adjuvant hormone therapy. This therapeutic approach converts many patients with initially unresectable disease to reasonable surgical candidates, with acceptable rates of loco-regional disease control. Induction of a pathological complete response (pCR) with modern chemotherapy agents or combined with immunotherapy, when applicable, should be one of the primary goals of neoadjuvant therapy in order to achieve better disease-free and overall survival in this subset of patients. Neoadjuvant chemotherapy is now standard for patients with locally advanced breast cancer, and this method of treatment has been extended to patients with earlier disease without affecting the treatment outcome. The objectives of this study were: (1) to conduct a phase II study to assess the efficacy and availability of epirubicin and paclitaxel in the neoadjuvant setting in women with locally advanced or high tumour-to-breast ratio breast cancer (no patient in either of these subgroups was a candidate for breast-conserving surgery prior to chemotherapy); (2) to evaluate the incidence of clinically relevant toxicity and, in particular, cardiac toxicity after treatment with an epirubicin + paclitaxel regimen in this group of patients.

Methods: In this open-label, phase II, single-centre trial carried out in a university-affiliated tertiary-care municipal hospital, the rate of objective response, evaluated by clinical and pathological examinations, was the primary endpoint of the study. Other endpoints were the rates of breast-conserving surgery, local recurrence, disease-free survival and overall survival. Sixty patients were enrolled from September 1998 to September 2003 with a median follow-up of 56 months (range 16–96). All 60 women met the criteria for inclusion and agreed to participate in the study. They were diagnosed as having locally advanced or high tumour-to-breast ratio breast cancer that did not initially permit breast-conserving surgery. Epirubicin 75 mg/m2 and paclitaxel 175 or 200 mg/m2 were administered for five courses. Rates of adverse events were also analysed.

Results: Eight patients experienced a pCR, five had a pathological partial response with an almost complete pathological response, and 39 were able to undergo breast-conserving surgery. Adverse effects were mostly of grade 1 or 2 severity. The most common adverse reactions were fatigue and neutropenic fever. One patient developed local recurrence during the median 56-month follow-up. Among examined biological markers, only estrogen receptor negativity was a strong predictor of a pCR. The rates of disease-free and overall survival following the neoadjuvant combination were similar for those who had tumours positive for the estrogen receptor and those who were negative for this.

Conclusion: Treatment with a combination of epirubicin and paclitaxel enabled lumpectomy in a substantial proportion of women who were previously deemed to not be suitable candidates for breast-conserving surgery. Clinical responses were not influenced by the initial tumour volume, and the only statistically significant predictor of pCR was the estrogen receptor status of the tumour.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hunt KK, Ames FC, Singletary SE, et al. Locally advanced noninflammatory breast cancer. Surg Clin North Am 1996; 76: 393–410

    Article  PubMed  CAS  Google Scholar 

  2. Sachelarie I, Grossbard ML, Chadha M, et al. Primary systemic therapy of breast cancer. Oncologist 2006; 11: 574–89

    Article  PubMed  CAS  Google Scholar 

  3. Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997; 15: 2483–93

    PubMed  CAS  Google Scholar 

  4. A’Hern RP, Smith IE, Ebbs SR. Chemotherapy and survival in advanced breast cancer patients: the inclusion of doxorubicin in Cooper type regimens. Br J Cancer 1993; 67: 801–5

    Article  PubMed  Google Scholar 

  5. Gianni L, Munzone E, Capri G, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 1995; 13: 2688–99

    PubMed  CAS  Google Scholar 

  6. Coukell AJ, Faulds D. Epirubicin: an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer. Drugs 1997; 53: 453–82

    Article  PubMed  CAS  Google Scholar 

  7. Conte PF, Baldini E, Gennari A, et al. Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer. J Clin Oncol 1997; 15: 2510–7

    PubMed  CAS  Google Scholar 

  8. Jain KK, Casper ES, Geller NL, et al. A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J Clin Oncol 1985; 3: 818–26

    PubMed  CAS  Google Scholar 

  9. Torti FM, Bristow MR, Howes AE. Reduced cardiotoxicity of doxorubicin delivered on a weekly schedule: assessment by endomyocardial biopsy. Ann Intern Med 1983; 99: 745–9

    PubMed  CAS  Google Scholar 

  10. ECOG Performance Status [online]. Available from URL: http://www.ecog.org/general/perf_stat.html [Accessed 2006 Oct 18]

  11. Bennett CL, Smith TJ, Weeks JC, et al. Use of hematopoietic colony-stimulating factors: the American Society of Clinical Oncology survey. J Clin Oncol 1996; 14: 2511–20

    PubMed  CAS  Google Scholar 

  12. Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 2006; 24: 1940–8

    Article  PubMed  Google Scholar 

  13. National Cancer Institute: Cancer Therapy Evaluation Program. Common toxicity criteria. Version 2.0. Bethesda (MD): National Institutes of Health 1999 Apr 30

    Google Scholar 

  14. Perez CA, Garcia DM, Kuske RR,et al. Breast stage T1 and T2 tumors. In: Perez CA, Brady LW, editors. Principles and practice of radiation oncology, 2nd ed. Philadelphia (PA): Lippincott Williams & Wi8lkins, 1992: 877–947

    Google Scholar 

  15. Gez E, Assaf N, Bar-Deroma R, et al. Postmastectomy electron-beam chest-wall irradiation in women with breast cancer. Int J Radiat Oncol Biol Phys 2004: 60: 1190-4

    Google Scholar 

  16. Kaufmann M, Klinga K, Runnembaum M, et al. In vitro adriamycin sensitivity test and hormonal receptors in primary breast cancer. Cancer 1980; 47: 2797–800

    Google Scholar 

  17. MacGrogan G, Mauriac L, Durand M, et al. Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, cerbB-2, MiB1, pS2 and GST. Br J Cancer 1996; 74: 1458–65

    Article  PubMed  CAS  Google Scholar 

  18. Colleoni M, Minchella I, Mazzaro lG, et al. Response to primary chemotherapy in breast cancer patients with tumors not expressing estrogen and progesterone receptors. Ann Oncol 2000; 11: 1057–9

    Article  PubMed  CAS  Google Scholar 

  19. Chang J, Powles TJ, Allred DC. Biologic markers as predictors of clinical outcome from systemic therapy for primary operable breast cancer. J Clin Oncol 1999; 17: 3058–63

    PubMed  CAS  Google Scholar 

  20. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998; 16: 2672–85

    PubMed  CAS  Google Scholar 

  21. Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17: 460–9

    PubMed  CAS  Google Scholar 

  22. Gogas H, Papadimitriou C, Kalofonos HP, et al. Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer: a phase II study by the Hellenic Cooperative Oncology Group. Ann Oncol 2002 Nov; 13(11): 1737–42

    Article  PubMed  CAS  Google Scholar 

  23. Fumoleau P, Tubiana-Hulin M, Romieu G, et al. A randomized phase II study of 4 or 6 cycles of adriamycin/Taxol® (paclitaxel) as neoadjuvant treatment of breast cancer [abstract]. Breast Cancer Res Treat 2001; 69: 298

    Google Scholar 

  24. Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003; 21: 4165–74

    Article  PubMed  CAS  Google Scholar 

  25. Bellino R, Cortese P, Danese S, et al. Epidoxorubicin and paclitaxel as primary chemotherapy for T > 3 cm and T4 breast cancer patients. Anticancer Res 2000; 20: 4825–8

    PubMed  CAS  Google Scholar 

  26. Moliterni A, Tarenzi E, Capri G, et al. Pilot study of primary chemotherapy with doxorubicin plus paclitaxel in women with locally advanced or operable breast cancer. Semin Oncol 1997; 24(5 Suppl. 17): S17–10–S17–4

    PubMed  CAS  Google Scholar 

  27. Untch M, Konecny M, Ditsch N, et al. Dose-dense sequential epirubicin-paclitaxel as preoperative treatment of breast cancer: results of a randomised AGO study [abstract]. Proc Am Soc Clin Oncol 2002; 21: 34a

    Google Scholar 

  28. Burstein HJ, Harris LN, Gelman R, et al. Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study. J Clin Oncol 2003; 21: 46–53

    Article  PubMed  CAS  Google Scholar 

  29. Wenzel C, Hussian D, Bartsch R, et al. Preoperative chemotherapy with epidoxorubicin and docetaxel plus trastuzumab in patients with primary breast cancer: a pilot study. J Cancer Res Clin Oncol 2004; 130: 400–4

    Article  PubMed  CAS  Google Scholar 

  30. Harris L, Burstein JH, Gelman R, et al. Preoperative trastuzumab and vinorelbine is a highly active, well-tolerated regimen for HER2 3+/FISH+stageII/III breast cancer. Proc Am Soc Clin Oncol 2003; 22: 86a

    Article  Google Scholar 

  31. Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005; 23: 3676–85

    Article  PubMed  CAS  Google Scholar 

  32. Mauriac L, Debled M, Durand M, et al. Neoadjuvant tamoxifen for hormone-sensitive non-metastatic breast carcinomas in early postmenopausal women. Ann Oncol 2002; 13: 293–8

    Article  PubMed  CAS  Google Scholar 

  33. Eierman W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 2001; 12: 1527–32

    Article  Google Scholar 

  34. Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1-and/ or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001; 19: 3808–16

    PubMed  CAS  Google Scholar 

  35. Gil MJ, Barnadas A, Cirera L, et al. Primary hormonal therapy with exemastane in patients with breast tumors >3 cm in diameter: results of a Spanish multicenter phase II trial. Proc Am Soc Clin Oncol 2004; 23: 603a

    Google Scholar 

Download references

Acknowledgements

None of the authors have any conflicts of interest and no external funding was received for this study. The authors thank Esther Eshkol for editorial assistance.

Author information

Authors and Affiliations

  1. Department of Oncology, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    David Sarid,  Ilan G. Ron, Felix Kovner, Rami Ben-Yosef, Yulia Grinberg, Natalie Maimon & Neora Yaal-Hahoshen

  2. The Breast Cancer Imaging Center, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Fani Sperber & Juliana Weinstein

  3. Surgery Department A, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Yona Stadler & Perry Kahan

  4. Department of Pathology, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Sylvia Marmor

Authors
  1. David Sarid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilan G. Ron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fani Sperber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yona Stadler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Perry Kahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Felix Kovner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rami Ben-Yosef
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sylvia Marmor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yulia Grinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Natalie Maimon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Juliana Weinstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Neora Yaal-Hahoshen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilan G. Ron.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sarid, D., Ron, I.G., Sperber, F. et al. Neoadjuvant Treatment with Paclitaxel and Epirubicin in Invasive Breast Cancer. Clin. Drug Investig. 26, 691–701 (2006). https://doi.org/10.2165/00044011-200626120-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-200626120-00003

Keywords

Search

Navigation