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01-12-2004 | Original Article

Docetaxel and high-dose epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer

Authors: E. Espinosa, S. Morales, P. Borrega, A. Casas, C. Madroñal, I. Machengs, J. A. Illarramendi, J. Lizón, J. A. Moreno, J. Belón, J. Janáriz, M. de la Puente, T. Checa, J. R. Mel, M. González Barón

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2004

Abstract

Purpose

Epirubicin and docetaxel are two of the most active drugs against breast carcinoma. As the achievement of a pathological complete response (pCR) is important for survival of patients with locally advanced disease, we used both drugs as neoadjuvant chemotherapy.

Patients and methods

Women with locally advanced or inflammatory breast cancer received epirubicin 120 mg/m² followed by docetaxel 75 mg/m², both on day 1, every 21 days for four cycles. Lenograstim was administered for 10 days in all cycles.

Results

Of 51 patients included, 50 received a total of 188 cycles, with a median of 4 per patient. The median age was 47 years, tumour stage was IIIA in 14 patients and IIIB in 36. Oestrogen receptors were positive in 65% of tumours. There were 10 clinical complete responses (20%) and 29 partial responses (58%). Surgery consisted of mastectomy in 40 patients and tumorectomy in 6. After surgery, 9 pCR were recorded (18%). One patient progressed and died soon after the end of chemotherapy. After a median follow-up of 22 months, the median disease-free survival was 33.7 months. Grade 3/4 neutropenia was observed in 32% of patients, anaemia in 6%, and thrombocytopenia in 4%. Five patients had febrile neutropenia. There were no toxic deaths or grade 4 nonhaematological toxicities.

Conclusions

Docetaxel plus high-dose epirubicin showed promising activity in patients with locally advanced and inflammatory breast cancer, at the cost of moderate toxicity.

Amat S, Bougnoux P, Penault-Llorca F, Fetissof F, Cure H, Kwiatkowski F, Achard JL, Body G, Dauplat J, Chollet P (2003) Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate. Br J Cancer 88:1339–1345CrossRefPubMed

Baldini E, Gardin G, Giannessi PG, Evangelista G, Roncella M, Prochilo T, Collecchi P, Rosso R, Lionetto R, Bruzzi P, Mosca F, Conte PF (2003) Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer. Ann Oncol 14:227–232CrossRefPubMed

Bonnefoi H, Biganzoli L, Cufer T, Mauriac L, Hamilton A, Schaefer P, Piccart M (2001) An EORTC phase I study of epirubicin in combination with fixed doses of cyclophosphamide and infusional 5-FU (CEF-infu) as primary treatment of large operable or locally advanced/inflammatory breast cancer. Breast Cancer Res Treat 70:55–63CrossRefPubMed

Cance WG, Carey LA, Calvo BF, Sartor C, Sawyer L, Moore DT, Rosenman J, Ollila DW, Graham 2nd M (2002) Long-term outcome of neoadjuvant therapy for locally advanced breast carcinoma: effective clinical downstaging allows breast preservation and predicts outstanding local control and survival. Ann Surg 236:295–302; discussion 302–303CrossRefPubMed

Chollet P, Charrier S, Brain E, Cure H, van Praagh I, Feillel V, de Latour M, Dauplat J, Misset JL, Ferriere JP (1997) Clinical and pathological response to primary chemotherapy in operable breast cancer. Eur J Cancer 33:862–866CrossRefPubMed

Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431–1439CrossRefPubMed

Dhingra K, Esparza-Guerra L, Valero V, et al (1999) A phase II randomized trial of dose-intensive, neoadjuvant 5FU, doxorubicin, cyclophosphamide with G-CSF in locally advanced breast cancer. Annual Meeting of the American Society of Clinical Oncology, vol 18. p 74

Estévez LG, Cuevas JM, Antón A, Florián J, López-Vega JM, Velasco A, Lobo F, Herrero A, Fortes J (2003) Weekly docetaxel as neoadjuvant chemotherapy for stage II and III breast cancer: efficacy and correlation with biological markers in a phase II, multicenter study. Clin Cancer Res 9:686–692PubMed

Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685PubMed

10.

Fountzilas G, Athanassiades A, Giannakakis T, Briasoulis E, Bafaloukos D, Kalogera-Fountzila A, Onienaoum A, Kalofonos H, Pectasides D, Andreopoulou E, Bamia C, Kosmidis P, Pavlidis N, Skarlos D (1997) A randomized study of epirubicin monotherapy every four or every two weeks in advanced breast cancer. A Hellenic Cooperative Oncology Group study. Ann Oncol 8:1213–1220CrossRefPubMed

11.

Friedrichs K, Holzel F, Janicke F (2002) Combination of taxanes and anthracyclines in first-line chemotherapy of metastatic breast cancer: an interim report. Eur J Cancer 38:1730–1738CrossRefPubMed

12.

Fumoleau P, Kerbrat P, Romestaing P, Fargeot P, Bremond A, Namer M, Schraub S, Goudier MJ, Mihura J, Monnier A, Clavere P, Serin D, Seffert P, Pourny C, Facchini T, Jacquin JP, Sztermer JF, Datchary J, Ramos R, Luporsi E (2003) Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancer patients: 10-year follow-up results of the French Adjuvant Study Group 01 trial. J Clin Oncol 21:298–305CrossRefPubMed

13.

Ganem G, Tubiana-Hulin M, Fumoleau P, Combe M, Misset JL, Vannetzel JM, Bachelot T, De Ybarlucea LR, Lotz V, Bendahmane B, Dieras V (2003) Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer. Ann Oncol 14:1623–1628CrossRefPubMed

14.

Gebbia V, Blasi L, Borsellino N, Caruso M, Leonardi V, Agostara B, Valenza R (2003) Paclitaxel and epidoxorubicin or doxorubicin versus cyclophosphamide and epidoxorubicin as first-line chemotherapy for metastatic breast carcinoma: a randomised phase II study. Anticancer Res 23:765–771PubMed

15.

Ghilezan N, Vitoc C, Tanasscu R, et al (1999) Epidoxorubicin and paclitaxel combination in neoadjuvant setting for stage IIB-IIIA breast cancer: preliminary results. Annual Meeting of the American Society of Clinical Oncology, vol 18. p 94

16.

van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224–4237PubMed

17.

Hamm J, Wilson J, Lembersky B, et al (2003) Neoadjuvant chemotherapy with gemcitabine, epirubicin and paclitaxel in locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group. San Antonio Breast Cancer Symposium

18.

Honig S (1996) Treatment of metastatic disease. In: Harris J, Lipman M, Morrow M, et al (eds) Diseases of the breast. Lippincott-Raven, Philadelphia, pp 669–734

19.

Konig E, Kurbacher C, Schwonzen M, Breidenbach M, Mallmann P (2002) A phase II study of dose-dense docetaxel and mitoxantrone in the treatment of patients with high-risk metastatic breast cancer. Anticancer Drugs 13:827–832CrossRefPubMed

20.

Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460–469PubMed

21.

Mamounas EP, Fisher B (2001) Preoperative (neoadjuvant) chemotherapy in patients with breast cancer. Semin Oncol 28:389–399CrossRefPubMed

22.

de Matteis A, Nuzzo F, D’Aiuto G, Labonia V, Landi G, Rossi E, Mastro AA, Botti G, De Maio E, Perrone F (2002) Docetaxel plus epidoxorubicin as neoadjuvant treatment in patients with large operable or locally advanced carcinoma of the breast: a single-center, phase II study. Cancer 94:895–901CrossRefPubMed

23.

Mauriac L, MacGrogan G, Avril A, Durand M, Floquet A, Debled M, Dilhuydy JM, Bonichon F (1999) Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol 10:47–52CrossRefPubMed

24.

Mey U, Gorschluter M, Ziske C, Kleinschmidt R, Glasmacher A, Schmidt-Wolf IG (2003) Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial. Anticancer Drugs 14:233–238CrossRefPubMed

25.

Millá-Santos A, Millá L, Rallo L, Solano V (2001) High-dose epirubicin plus docetaxel at standard dose with lenograstim support as first-line therapy in advanced breast cancer. Am J Clin Oncol 24:138–142CrossRefPubMed

26.

Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschenes L, Douma J, Vandenberg TA, Rapoport B, Rosso R, Trillet-Lenoir V, Drbal J, Molino A, Nortier JW, Richel DJ, Nagykalnai T, Siedlecki P, Wilking N, Genot JY, Hupperets PS, Pannuti F, Skarlos D, Tomiak EM, Murawsky M, Alakl M, Aapro M, et al (1999) Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol 17:1413–1424

27.

Petit T, Borel C, Theobald S, Serin D, Rodier JF, Prevot G, Brettes JP, Klein T (2003) Randomized multicentric study of perioperative chemotherapy with mitoxantrone in early breast cancer. Ann Surg Oncol 10:369–375CrossRefPubMed

28.

Pouillart P, Fumoleau P, Romieu G, et al (1999) Final results of a phase II randomized, parallel study of doxorubicin/cyclophosphamide and doxorubicin/Taxol as neoadjuvant treatment of local-regional breast cancer. Annual Meeting of the American Society of Clinical Oncology, vol 18. p 73

29.

Schneeweiss A, Geberth M, Sinn H-P, et al (2003) The triplet gemcitabine, epirubicin and docetaxel as primary systemic chemotherapy in primary breast cancer T2-4,N0-2,M0: final primary endpoint analysis of a multicentric phase I/II trial. San Antonio Breast Cancer Symposium

30.

Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20:1456–1466CrossRefPubMed

31.

Tchen N, Juffs HG, Downie FP, Yi QL, Hu H, Chemerynsky I, Clemons M, Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF (2003) Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol 21:4175–4183CrossRefPubMed

32.

Trudeau ME (2001) Optimizing adjuvant breast cancer chemotherapy: rationale for the MA.21 study. Oncology (Huntingt) 15:7–13

33.

Valero V, Esteva J, Sahin A, et al (2000) Phase II trial of neoadjuvant chemotherapy with docetaxel and doxorubicin, surgery, adjuvant CMF, and radiotherapy +/− tamoxifen in locally advanced breast cancer. San Antonio Breast Cancer Symposium

34.

Wenzel C, Locker GJ, Pluschnig U, Zielinski CC, Rudas M, Oberhuber G, Gnant MF, Taucher S, Jakesz R, Steger GG (2002) Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer. Cancer Chemother Pharmacol 50:155–159CrossRefPubMed

35.

Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B (2001) Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr 96–102

36.

Zambetti M, Moliterni A, Materazzo C, Stefanelli M, Cipriani S, Valagussa P, Bonadonna G, Gianni L (2001) Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation. J Clin Oncol 19:37–43PubMed

Title: Docetaxel and high-dose epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer
Authors: E. Espinosa
S. Morales
P. Borrega
A. Casas
C. Madroñal
I. Machengs
J. A. Illarramendi
J. Lizón
J. A. Moreno
J. Belón
J. Janáriz
M. de la Puente
T. Checa
J. R. Mel
M. González Barón
Publication date: 01-12-2004
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2004
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-004-0830-1

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