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A multicenter prospective phase II trial of neoadjuvant epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin–docetaxel with or without trastuzumab in locally advanced breast cancer

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Abstract

Purpose

To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with and without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC).

Methods

Eighty patients with LABC (T2–T4, N0–N2, M0) were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin and docetaxel, plus trastuzumab if HER2 positive. The primary endpoint was pathologic complete response (pCR) in breast and axilla in separate HER2-negative and HER2-positive cohort.

Results

Eighty patients were evaluable for analysis of which 51 were HER2 negative and 29 HER2 positive: median age: 43 years, premenopausal: 82 %, median tumor size: 7.0 cm (4–10), stage IIB: 25 % and IIIA/IIIB: 75 %, both ER/PR positive: 56 %, HER2 positive (3+) by IHC staining: 36 %. Clinical complete response was seen in 48 %, and clinical partial response was seen in 52 %. Overall the pathologic complete response (pCR) was 36 % in breast, 64 % in axilla, and 32 % in both breast and axilla. Analysis of pCR in breast and axilla, as a function of the hormonal receptor (HR) and HER2, was as follows: HR+/HER2: 11 %; HR+/HER+: 56 %; HR/HER2: 36 %; HR/HER2+: 62 %.

Conclusion

In this series of locally advanced breast cancer, the combination of (FEC100) followed by cisplatin/docetaxel with and without trastuzumab was very active obtaining an impressive rate of pCR, particularly in HER2-positive and triple negative disease, which merits further investigation.

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References

  1. Von Minckwitz G, Kaufmann M, Kuemmel S, for the GBG and AGO-B Study Groups et al (2011) Correlation of various pathologic complete response (pCR) definitions with long term outcome and the prognostic value of pCR in various breast cancer subtypes: results from the German neoadjuvant meta-analysis. J clin Oncol 29(suppl):1028

    Google Scholar 

  2. Montagna E, Bagnardi V, Rotmensz N et al (2010) Pathologic complete response after preoperative systemic therapy and outcome: relevance of clinical and biologic baseline features. Breast Cancer Res Treat 124:689–699

    Article  PubMed  Google Scholar 

  3. Bear HD, Anderson S, Smith RE et al (2006) Sequential preoperative or postoperative Docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: national surgical adjuvant breast and bowel project protocols B-27. J Clin Oncol 24:2019–2027

    Article  PubMed  CAS  Google Scholar 

  4. Sachelaria I, Grossbard MI, Chadha M et al (2006) Primary systemic therapy of breast cancer. Oncologist 11:564–589

    Google Scholar 

  5. Kaufmann M, Von Minckwitz G, Mamounas EP et al (2012) Recommendation from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol 19:1508–1516

    Article  PubMed  Google Scholar 

  6. Bear HD, Anderson S, Brown A et al (2003) 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 21:4165–4174

    Article  PubMed  CAS  Google Scholar 

  7. Sachelarie I, Grossbard ML, Chadha M et al (2006) Primary systemic therapy of breast cancer. Oncologist 11:574–589

    Article  PubMed  CAS  Google Scholar 

  8. Kuerer HM, Newman LA, Smith TL et al (1999) Clinical course of breast cancer patients with complete pathologic primary and axillary lymph node response to doxorubicin based neoadjuvant chemotherapy. J Clin Oncol 17:460–469

    PubMed  CAS  Google Scholar 

  9. Von Minckwitz G, Blohmer JU, Raab G et al (2005) In vivo chemosensitivity adopted preoperative chemotherapy in patients with early stage breast cancer: the GEPARTRIO pilot study. Ann Oncol 16:56–63

    Article  Google Scholar 

  10. O’Regan RM, Von Roenn JH, Carleson RW et al (2005) Final results of phase II trial of preoperative TAC in stage III breast cancer. Clin Breast Cancer 6:163–168

    Article  PubMed  Google Scholar 

  11. Buzdar AU, Ibrahim NK, Francis D et al (2005) significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23:3676–3685

    Article  PubMed  CAS  Google Scholar 

  12. Gianni L, Eiermann W, Semiglazov V et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with parallel HER2-negative cohort. Lancet 375:377–384

    Article  PubMed  CAS  Google Scholar 

  13. Untch M, Rezai M, Loibl S et al (2010) Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from GeparQuattrostudy. J Clin Oncol 28:2024–2031

    Article  PubMed  CAS  Google Scholar 

  14. Von Minckwitz G, Loibl S, Untch M et al (2012) What is the current standard of care for antiHER2 neoadjuvant therapy in breast cancer? Oncology 26:20–26

    Google Scholar 

  15. Crown JP (2001) The platinum agents: a role in breast cancer treatment. Semin Oncol 28:28–37

    Article  PubMed  CAS  Google Scholar 

  16. Zoli W, Flamigi A, Frassinineti GL et al (1995) In vitro activity of taxol and taxotere in comparison with doxorubicin and cisplatin on primary cell cultures of human breast cancer. Breast Cancer Res Treat 34:63–69

    Article  PubMed  CAS  Google Scholar 

  17. Belani C, Lynch T (2000) Docetaxel in combination with platinum in patients with non small cell lung cancer: trial data and implications for clinical management. Semin Oncol 28:10–14

    Google Scholar 

  18. Engblom P, Rantaen V, Kulmala J et al (1999) Additive and supra-additive cytotoxicity of cisplatin—taxane combinations in ovarian carcinoma cell lines. Br J Cancer 79:286–292

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Ezzat AA, Raja MA, Berry J et al (1997) A phase II trial of circadian timed paclitaxel and cisplatin therapy in metastatic breast cancer. Ann Oncol 8:663–667

    Article  PubMed  CAS  Google Scholar 

  20. Ezzat AA, Ibrahim EM, Ajarim DS et al (2000) High complete pathologic response in locally advanced breast cancer using paclitaxel and cisplatin. Breast Cancer Res Treat 62:237–244

    Article  PubMed  CAS  Google Scholar 

  21. Ezzat AA, Ibrahim EM, Ajarim DS et al (2004) Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients. Br J Cancer 90:968–974

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Al-Tweigeri TA, Ajarim DS, Alsayed AA et al (2010) Prospective phase II study of neoadjuvant doxorubicin followed by cisplatin/docetaxel in locally advanced breast cancer. Med Oncol 27:571–577

    Article  PubMed  CAS  Google Scholar 

  23. Buzdar AU, Singletary SE, Theriault RL et al (1999) Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 17:3412–3417

    PubMed  CAS  Google Scholar 

  24. Miller KD, MCatskill-Stevens W, Sisk J et al (1999) Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: a randomized pilot trial of the Hoosier Oncology Group. J Clin Oncol 17:3033–3037

    PubMed  CAS  Google Scholar 

  25. Bujanda DA, Sarmiento UB, Suarez MAC et al (2006) Epirubicin, cyclophosphamide and weekly paclitaxel as neoadjuvant chemotherapy for stage II and III breast cancer. J Cancer Res Clin Oncol 132:332–338

    Article  Google Scholar 

  26. Evans TR, Yellowlees A, Foster E et al (2005) Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an Anglo-Celtic Cooperative Oncology Group study. J Clin Oncol 23:2988–2995

    Article  PubMed  CAS  Google Scholar 

  27. Kelly H, Kimmick G, Dees EC et al (2006) Response and cardiac toxicity of trastuzumab given in conjunction with weekly paclitaxel after doxorubicin/cyclophosphamide. Clin Breast Cancer 7:237–243

    Article  PubMed  CAS  Google Scholar 

  28. Rocca A, Peruzzotti G, Ghisini R et al (2006) A randomized phase II trial comparing preoperative plus perioperative chemotherapy with preoperative chemotherapy in patients with locally advanced breast cancer. Anticancer Drugs 17:1201–1209

    Article  PubMed  CAS  Google Scholar 

  29. Tiezzi DG, Andrade JM, Ribeiro-Silva A et al (2007) HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination. BMC Cancer 7:36

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gogas H, Papadimitriou C, Kalofonos HP et al (2002) 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 13:1737–1742

    Article  PubMed  CAS  Google Scholar 

  31. Rossi D, Baldelli AM, Casadei V et al (2008) Neoadjuvant chemotherapy with low dose of pegylated liposomal doxorubicin plus weekly paclitaxel in operable and locally advanced breast cancer. Anticancer Drugs 19:733–737

    Article  PubMed  CAS  Google Scholar 

  32. Artioli G, Mocellin S, Borgato L et al (2010) Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer. Anticancer Res 30:3817–3821

    PubMed  CAS  Google Scholar 

  33. Dellapasqua S, Mazza M, Rosa D et al (2011) Pegylated liposomal doxorubicin in combination with low-dose metronomic cyclophosphamide as preoperative treatment for patients with locally advanced breast cancer. Breast 20:319–323

    Article  PubMed  Google Scholar 

  34. Taguchi T, Masuda N, Nakayama T et al (2010) Phase II trial in Japan of sequential administration of weekly paclitaxel followed by FEC as neoadjuvant chemotherapy for locally advanced breast cancer (KBCSG0206 trial: Kinki Breast Cancer Study Group (KBCSG)). Oncology 78:302–308

    Article  PubMed  CAS  Google Scholar 

  35. Therasse P, Mauriac L, Welnicka-Jaskiewicz M et al (2003) Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCICSAKK multicenter study. J Clin Oncol 21:843–850

    Article  PubMed  CAS  Google Scholar 

  36. Berrutoni A, Brizzi MP, Generali D et al (2008) Pre-surgical systemic treatment of nonmetastatic breast cancer: facts and open questions. Oncologist 13:1137–1148

    Article  Google Scholar 

  37. Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long term clinical benefits in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172

    Article  PubMed  Google Scholar 

  38. Ando M, Yamauchi H, Aogi K et al (2014) 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. doi:10.1007/s10549-014-2947-1

    PubMed Central  Google Scholar 

  39. Buzdar AU, Valero V, Theriault RL et al (2003) Pathologic complete response to chemotherapy is related to hormone receptor status. Breast Cancer Res Treat 88:S69 (abstr 302)

    Google Scholar 

  40. Chang HR, Slamon D, Prati R, et al (2006) A phase II study of neoadjuvant docetaxel carboplatin ± trastuzumab in locally advanced breast cancer: response and cardiotoxicity. J Clin Oncol 24(18S) (abstract 10515)

  41. Feton MA, Ries LM, Strenger R, et al (2005) Frequent pathologic complete response seen with neoadjuvant q4 week carboplatin and weekly paclitaxel plus trastuzumab in resectable and locally advanced breast cancer: a Brown university Oncology Group study. SABCS (abstract 5054)

  42. Metha RS, Schubber T, Hsiang D, et al (2005) High pathologic complete remission rates with paclitaxel and carboplatin ± trastuzumab following dose dense doxorubicin and cyclophosphamide supported with GM-CSF in breast cancer. SABCS (abstract 5056)

  43. Gianni L, Eiermann W, Semiglazov V, et al (2014) Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 15:640–647

    Article  PubMed  CAS  Google Scholar 

  44. Hurley J, Reis IM, Rodgers SE et al (2013) The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients. Breast Cancer Res Treat 138:783–794

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Grant from King Faisal Specialist Hospital and Research Center Riyadh, Department of Medicine Faculty of Medicine, Kuwait University, King Abdul-Aziz Hospital and Oncology Center Jeddah, Tawam Hospital, AL-Ain, Abu Dhabi UAE, King Abdul-Aziz Medical City Riyadh, King Fahad Medical City Riyadh, Kuwait Cancer Center (RAC # 2061048). The authors thank the oncology data unit at King Faisal Specialist Hospital and Research Center Riyadh for their support during the preparation of the article, especially Tusneem Elhassan and Romelia Retuta. We are grateful to Dr Mohamed Mohiuddin and Dr. Hazem Ghebeh for the critical review of the manuscript and their valuable comments.

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Correspondence to Taher AL-Tweigeri.

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AL-Tweigeri, T., AlSayed, A., Alawadi, S. et al. A multicenter prospective phase II trial of neoadjuvant epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin–docetaxel with or without trastuzumab in locally advanced breast cancer. Cancer Chemother Pharmacol 77, 147–153 (2016). https://doi.org/10.1007/s00280-015-2906-5

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