Advertisement

Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab in patients with primary breast cancer: a pilot study

  • Catharina Wenzel
  • Dagmar Hussian
  • Rupert Bartsch
  • Ursula Pluschnig
  • Gottfried J. Locker
  • Margarethe Rudas
  • Michael F. Gnant
  • Raimund Jakesz
  • Christoph C. Zielinski
  • Guenther G. Steger
Original Paper

Abstract

Purpose

Combining anthracyclines and taxanes are to date the most active cytotoxic treatment option in the neoadjuvant and palliative therapy of breast cancer patients. Adding trastuzumab to these cytotoxic agents can improve outcome for women with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. We conducted a pilot study of preoperative epidoxorubicin and docetaxel plus trastuzumab in outpatient patients suffering from breast cancer.

Patients and methods

Fourteen consecutive patients were enrolled in this prospective clinical pilot trial. Preoperative treatment consisted of weekly trastuzumab (4 mg/kg body-weight loading dose, 2 mg/kg/week maintenance dose), in combination with weekly epidoxorubicin (30 mg/m2 body surface area [BSA]) and docetaxel (35 mg/m2 BSA) once a week for 6 weeks followed by 1 week off therapy.

Results

Patients received a total of 30 cycles (median: 2 cycles, range: 2–3 cycles) of this therapeutic regimen. Outpatient epidoxorubicin and docetaxel plus trastuzumab were well tolerated. A major response to this preoperative therapy regimen could be demonstrated in 12 of 14 patients (86%) leading to breast-conserving surgery in 11 of 14 patients (79%).

Conclusions

We conclude that outpatient epidoxorubicin and docetaxel plus trastuzumab are safe in the neoadjuvant treatment of patients suffering from breast cancer, based on a favorable side-effect and activity profile. Thus, this regimen can be considered for further clinical trials.

Keywords

Breast cancer Neoadjuvant Docetaxel Epidoxorubicin Trastuzumab. 

References

  1. Bellot R, Robert J, Dieras V, Misset JL, Baille P, Bozec L, Vernillet L, Riva A, Azli N, Pouillart P (1998) Taxotere does not change the pharmacokinetic profile of doxorubicin and doxorubicinol. Proc Am Soc Clin Oncol 17:221a (Abstract 853)Google Scholar
  2. Burstein HJ, Manola J, Younger J, Parker LM, Bunell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP (2000) Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol 18:1212–1219PubMedGoogle Scholar
  3. Burstein HJ, Harris LN, Gelman R, Lester SC, Nunes RA, Kaelin CM, Parker LM, Ellisen LW, Kuter I, Gadd MA, Christian RL, Kennedy PR, Borges VF, Bunnell CA, Younger J, Smith BL, Winer EP (2003) 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 21:46–53CrossRefGoogle Scholar
  4. Dieras V, Chevallier B, Kerbrat P, Krakowski I, Roche H, Misset JL, Lentz MA, Azli N, Murawsky M, Riva A, Pouillart P, Fumoleau P (1996) A multicentre phase II study of docetaxel 75 mg/m2 as first-line chemotherapy for patients with advanced breast cancer: report of the Clinical Screening Group of the EORTC. Br J Cancer 74:650–656PubMedGoogle Scholar
  5. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV (1997) Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15:2483–2493PubMedGoogle Scholar
  6. Gennari A, Salvadori B, Donati S, Bengala C, Orlandini C, Danesi R, Del Tacca M, Bruzzi P, Conte PF (1999) Cardiotoxicity of epirubicin/paclitaxel-containing regimens: Role of cardiac risk factors. J Clin Oncol 17:3596–3602PubMedGoogle Scholar
  7. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ (2003) Cancer statistics 2003. J Clin Oncol 53:5–26Google Scholar
  8. Luporsi E, Vanlemmens L, Coudert B, Mayer F, Bonneterre J, Petit T, Borel C, Hirsch M, Bey P (2000) 6 cycles of FEC 100 vs 6 cycles of epirubicin–docetaxel (ED) as neoadjuvant chemotherapy in operable breast cancer patients (Pts): Preliminary results of a randomized phase II trial of GIREC SO1. Proc Am Soc Clin Oncol 19:92a (Abstract 355)Google Scholar
  9. Mencel PJ, Lerner WA, Topilow AA, Greenberg SN, Pomponi DA, Virdi JK, Kuo Y (2000) Adjuvant chemotherapy of sequential docetaxel (D) and adriamycin (A) in patients with stage II and III completely resected breast cancer. Proc Am Soc Clin Oncol, 19:143a (Abstract 563)Google Scholar
  10. Milla-Santos A, Anton-Aparicio A, Gonzalez-Baron M, Milla I, Solano V, Rallo I (2000) Docetaxel (D) plus high dose epirubicin (E) with lenograstim (L) support as first line therapy in advanced breast cancer (ABC). A phase II study. Proc Am Soc Clin Oncol 19:107a (Abstract 413)Google Scholar
  11. Nabholtz JM, Riva A (2001) Taxane/anthracycline combinations: setting a new standard in breast cancer? Oncologist 6:5–12PubMedGoogle Scholar
  12. Norton L, Slamon D, Leyland-Jones B, Wolter J, Fleming T, Eirmann W, Baselga J, Mendelsohn J, Bajamonde A, Ash M, Shak S (1999) Overall survival (OS) advantage to simultaneous chemotherapy (CRx) plus the humanized anti-HER2 monoclonal antibody Herceptin (H) in HER2-overexpressing (HER2+) metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 18:127a (Abstract 483)Google Scholar
  13. Pazos C, Mickiewicz E, Di Notto MR, Coppola F, Ventriglia M, Jovtis S, Balbiani L, Lewi D, Rondinon M, Temperley G, Trigo M, Bertoncin AM, Pascual M, Uranga G, Cazap E, Breier S, Grasso S, Estevez R, Triguboff E, Alvarez A, Suarez A (1999) Phase II of doxorubicin/taxol in metastatic breast cancer. A Multicenter Taxol Group. Breast Cancer Res Treat 55:91–96PubMedGoogle Scholar
  14. Piccart MJ, Biganzoli L, Di Leo A (2000) The impact of chemotherapy dose density and dose intensity on breast cancer outcome: What have we learned? Eur J Cancer 36: S4–10CrossRefPubMedGoogle Scholar
  15. Reichman BS, Seidman AD, Crown JPA, Heelan R, Hakes TB, Lebwohl DE, Gilewski TA, Surbone A, Currie V, Hudis CA, Yao TJ, Klecker R, Jamis-Dow C, Collins J, Quinlivan S, Berkery R, Toomasi F, Canetta R, Fisherman J, Arbuck S, Norton L (1993) Paclitaxel and recombinant human granulocyte-colony stimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol 11:1943–1951PubMedGoogle Scholar
  16. Scholl SM, Fourquet A, Asselain B, Pierga JY, Vilcoq JR, Durand JC, Dorval T, Palangie T, Jouve M, Beuzeboc A, Garcio-Giralt E, Salmon RJ, De La Rochefordiere A, Campana F, Pouillart P (1994) Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast-conserving surgery: preliminary results of a randomised trial: S6. Eur J Cancer 30A: 645–652CrossRefPubMedGoogle Scholar
  17. Seidman AD, Hudis CA, Albanel J, Tong W, Tepler I, Currie V, Moynahan ME, Theodoulou M, Gollub M, Baselga J, Norton L (1998) Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 16:3353–3361PubMedGoogle Scholar
  18. Seidman AD, Fornier MN, Esteva FJ, Tan L, Kaptain S, Bach A, Panageas KS, Arroyo C, Valero V, Currie V, Gilewski T, Theodoulou M, Moynahan ME, Moasser M, Sklarin N, Dickler M, D‘Andrea G, Cristofanilli M, Rivera E, Hortobagyi GN, Norton L, Hudis CA (2001) Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenptype and gene amplification. J Clin Oncol 19:2587–2595PubMedGoogle Scholar
  19. Slamon D, Leyland-Jones B, Shak S, Bajamonde A, Fleming T, Eiermann W, Wolter J, Baselga J, Norton L (1998) Addition of Herceptin (humanized anti-HER2 antibody) to first-line chemotherapy for HER2 overexpressing metastatic breast cancer (HER2+/MBC) markedly increases anticancer activity: A randomized, multinational controlled phase III trial. Proc A Soc Clin Oncol, 17:98a (Abstract 377)Google Scholar
  20. Sparano JA, O’Neill A, Schaefer PL, Falkson CI, Wood WC (2000) Phase II trial of doxorubicin and docetaxel plus granulocyte colony-stimulating factor in metastatic breast cancer: Eastern Cooperative Oncology Group Study E1196. J Clin Oncol 18:2369–2377PubMedGoogle Scholar
  21. Steger GG, Wenzel C, Schmidinger M, Locker GJ, Rudas M, Taucher S, Gnant M, Jakesz R (2000) HER2 status predicts complete pathological response (pCR) in primary, operable breast cancer (BC) treated with neoadjuvant epirubicin/docetaxel + G-CSF. Breast Cancer Res Treat 64:31 (Abstract 23)Google Scholar
  22. Wenzel C, Schmidinger M, Locker GJ, Taucher S, Gnant M, Jakesz R, Steger GG (1999) Clinical phase II-evaluation of neoadjuvant, cytostatic combination chemotherapy with docetaxel and epidoxorubicin in female breast cancer patients (T1–4, N0–2, M0). Wien Klin Wochenschr 111:843–850PubMedGoogle Scholar
  23. Wenzel C, Locker GJ, Pluschnig U, Zielinski CC, Rudas M, Oberhuber G, Gnant MF, Taucher S, Jakesz R, Steger GG (2002a) Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer. Cancer Chemother Pharmacol 50:155–159CrossRefPubMedGoogle Scholar
  24. Wenzel C, Locker GJ, Schmidinger M, Rudas M, Taucher S, Gnant MF, Jakesz R, Steger GG (2002b) Combined analysis of two phase II trials in patients with primary and advanced breast cancer with epidoxorubicin and docetaxel+granulocyte colony stimulating factor. Anticancer Drugs 13:67–74PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Catharina Wenzel
    • 1
  • Dagmar Hussian
    • 1
  • Rupert Bartsch
    • 1
  • Ursula Pluschnig
    • 1
  • Gottfried J. Locker
    • 1
  • Margarethe Rudas
    • 2
  • Michael F. Gnant
    • 3
  • Raimund Jakesz
    • 3
  • Christoph C. Zielinski
    • 1
    • 4
    • 5
  • Guenther G. Steger
    • 1
  1. 1.Department of Internal Medicine I, Division of OncologyUniversity Hospital of ViennaViennaAustria
  2. 2.Department of PathologyUniversity Hospital of ViennaViennaAustria
  3. 3.Department of SurgeryUniversity Hospital of ViennaViennaAustria
  4. 4.Chair of Medical Experimental OncologyUniversity Hospital of ViennaViennaAustria
  5. 5.Ludwig Boltzmann Institute for Clinical OncologyUniversity Hospital of ViennaViennaAustria

Personalised recommendations