Skip to main content

Advertisement

Log in

A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer

  • Clinical Trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We aimed to determine the efficacies of a non-anthracycline-containing regimen, docetaxel/capecitabine (TX), in comparison with an anthracycline-containing regimen, doxorubicin/cyclophosphamide (AC), as primary chemotherapy for node-positive early stage breast cancer. In this phase-III single center randomized study, we randomized 209 women with axillary node positive, stage II/III breast cancer to receive four cycles of either TX or AC followed by surgery and cross-over to the other treatment as an adjuvant therapy. The primary endpoint was tumor pathologic complete response (pCR). Clinical response rates, toxicity profiles, disease free survival (DFS), and overall survival were secondary objectives. In total, 204 patients had clinical and radiological evaluation of response, and underwent surgery. Compared with AC, TX increased pCR in primary tumors (21% vs. 10%, respectively, P = 0.024) and clinical response (84% vs. 65%, P = 0.003). TX was associated with less nausea and vomiting, but more stomatitis, diarrhea, myalgia, and skin/nail changes than AC. With a median follow-up of 37 months, there was no significant difference in DFS by treatment groups (P = 0.932). Fewer patients developed recurrence who achieved pCR in lymph node (LN) (P = 0.025; hazard ratio, 0.189; 95% CI, 0.044–0.815) in the multivariate analysis. TX showed superior efficacies to AC with increased pathologic and clinical complete response rates. Although these findings did not translate into a gain in DFS, the patients who achieved pCR in LN developed significantly less recurrence.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. 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 16:2672–2685

    PubMed  CAS  Google Scholar 

  2. Machiavelli MR, Romero AO, Perez JE, Lacava JA, Dominguez ME, Rodriguez R, Barbieri MR, Romero Acuna LA, Romero Acuna JM, Langhi MJ, Amato S, Ortiz EH, Vallejo CT, Leone BA (1998) Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am 4:125–131

    PubMed  CAS  Google Scholar 

  3. Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, Singletary SE, Theriault RL, McNeese MD, Ames F, Walters R, Hortobagyi GN (2004) The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol 22:2294–2302

    Article  PubMed  CAS  Google Scholar 

  4. 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 17:460–469

    PubMed  CAS  Google Scholar 

  5. Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN (2005) 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 23:3676–3685

    Article  PubMed  CAS  Google Scholar 

  6. Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N (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. 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 20:1456–1466

    Article  PubMed  CAS  Google Scholar 

  8. Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N (2006) Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24:2019–2027

    Article  PubMed  CAS  Google Scholar 

  9. Horan PG, McMullin MF, McKeown PP (2006) Anthracycline cardiotoxicity. Eur Heart J 27:1137–1138

    Article  PubMed  CAS  Google Scholar 

  10. Zucchi R, Danesi R (2003) Cardiac toxicity of antineoplastic anthracyclines. Curr Med Chem Anticancer Agents 3:151–171

    Article  PubMed  CAS  Google Scholar 

  11. Perez EA, Rodeheffer R (2004) Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22:322–329

    Article  PubMed  CAS  Google Scholar 

  12. Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J (2005) Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 23:7811–7819

    Article  PubMed  CAS  Google Scholar 

  13. Jones SE, Savin MA, Holmes FA, O’Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24:5381–5387

    Article  PubMed  CAS  Google Scholar 

  14. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Pawlicki M, Chan A, Smylie M, Liu M, Falkson C, Pinter T, Fornander T, Shiftan T, Valero V, Mackey J, Tabah-Fisch I, Buyse M, Lindsay M, Riva A, Bee V, Pegram M, Press M, Crown J (2006) BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients (abstr 52). In: Proceedings of the 29th Annual San Antonio Breast Cancer Symposium, San Antonio, TX

  15. Fumoleau P, Largillier R, Clippe C, Dieras V, Orfeuvre H, Lesimple T, Culine S, Audhuy B, Serin D, Cure H, Vuillemin E, Morere JF, Montestruc F, Mouri Z, Namer M (2004) Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 40:536–542

    Article  PubMed  CAS  Google Scholar 

  16. Talbot DC, Moiseyenko V, Van Belle S, O’Reilly SM, Alba Conejo E, Ackland S, Eisenberg P, Melnychuk D, Pienkowski T, Burger HU, Laws S, Osterwalder B (2002) Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines. Br J Cancer 86:1367–1372

    Article  PubMed  CAS  Google Scholar 

  17. Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H (1998) Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 4:1013–1019

    PubMed  CAS  Google Scholar 

  18. O’Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823

    Article  PubMed  CAS  Google Scholar 

  19. Bonadonna G, Valagussa P, Zucali R, Salvadori B (1995) Primary chemotherapy in surgically resectable breast cancer. CA Cancer J Clin 45:227–243

    Article  PubMed  CAS  Google Scholar 

  20. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  21. Inoue T, Yutani K, Taguchi T, Tamaki Y, Shiba E, Noguchi S (2004) Preoperative evaluation of prognosis in breast cancer patients by [(18)F]2-Deoxy-2-fluoro-D-glucose-positron emission tomography. J Cancer Res Clin Oncol 130:273–278

    Article  PubMed  Google Scholar 

  22. Wahl RL, Siegel BA, Coleman RE, Gatsonis CG (2004) Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging breast cancer with PET Study Group. J Clin Oncol 22:277–285

    Article  PubMed  Google Scholar 

  23. Zornoza G, Garcia-Velloso MJ, Sola J, Regueira FM, Pina L, Beorlegui C (2004) 18F-FDG PET complemented with sentinel lymph node biopsy in the detection of axillary involvement in breast cancer. Eur J Surg Oncol 30:15–19

    Article  PubMed  CAS  Google Scholar 

  24. Bonadonna G, Valagussa P, Brambilla C, Ferrari L, Moliterni A, Terenziani M, Zambetti M (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16:93–100

    PubMed  CAS  Google Scholar 

  25. Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM (2006) Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24:1037–1044

    Article  PubMed  Google Scholar 

  26. Colleoni M, Viale G, Zahrieh D, Pruneri G, Gentilini O, Veronesi P, Gelber RD, Curigliano G, Torrisi R, Luini A, Intra M, Galimberti V, Renne G, Nole F, Peruzzotti G, Goldhirsch A (2004) Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res 10:6622–6628

    Article  PubMed  CAS  Google Scholar 

  27. Avril N, Rose CA, Schelling M, Dose J, Kuhn W, Bense S, Weber W, Ziegler S, Graeff H, Schwaiger M (2000) Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 18:3495–3502

    PubMed  CAS  Google Scholar 

  28. Kim SJ, Kim SK, Lee ES, Ro J, Kang S (2004) Predictive value of [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy. Ann Oncol 15:1352–1357

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Supported in part by NCC Grant 0210150 and Korean Health 21 R&D Project Grant by Ministry of Heath and Welfare, Republic of Korea (0412-CR01-0704-0001). Sanofi-Aventis and Roche Korea provided the study drugs, Taxotere and Xeloda, respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jungsil Ro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, K.S., Ro, J., Nam, BH. et al. A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer. Breast Cancer Res Treat 109, 481–489 (2008). https://doi.org/10.1007/s10549-007-9672-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9672-y

Keywords

Navigation