Skip to main content

Advertisement

Log in

A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer

A Hellenic Cooperative Oncology Group study

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

Abstract

Background Effective anthracycline-free combinations need to be evaluated in metastatic breast cancer (MBC), due to the increased number of patients treated with anthracycline-based adjuvant chemotherapy. Patients and methods Patients with MBC were randomized to paclitaxel and carboplatin (PCb) every 3 weeks or docetaxel and gemcitabine (GDoc) every 3 weeks or weekly paclitaxel (Pw). Trastuzumab was given to patients with HER-2 over-expressing tumors. The primary endpoint of the study was survival. Quality of life (QoL) and cost were assessed. Results Totally, 416 eligible patients entered the study. Median survival times were 29.9 months for PCb, 26.9 for GDoc and 41.0 for Pw (P = 0.037). According to multivariate analysis, adjuvant chemotherapy, >1 metastatic sites, lack of maintenance hormonal therapy, and worse performance status (PS) were significant adverse prognostic factors for survival, while Pw when compared to GDoc improved survival (P = 0.03), as well as when compared to PCb in the subgroup of patients with PS = 1 (P = 0.01, treatment by PS interaction P = 0.03). No significant differences in terms of time to progression were found. Severe myelotoxicity and mucositis were more frequent with GDoc, while severe neuropathy with PCb and Pw. QoL changes did not differ significantly between treatment groups, while cost analysis favored Pw. Conclusions Pw appears to be the most preferable choice among the 3 anthracycline-free taxanes-based regimens tested in the present study.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  2. Ellis MJ, Hayes DF, Lippman M (2000) Treatment in metastatic breast cancer. In: Harris JR (ed) Disease of the breast, 2nd edn. Lippincot Williams & Wilkins, Philadelphia, pp 749–797

    Google Scholar 

  3. Fountzilas G, Dimopoulos AM, Papadimitriou C et al (1998) First-line chemotherapy with paclitaxel by three-hour infusion and carboplatin in advanced breast cancer (final report): a phase II study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 9:1031–1034

    Article  PubMed  CAS  Google Scholar 

  4. Perez EA, Hillman DW, Stella PJ et al (2000) A phase II study of paclitaxel plus carboplatin as first-line chemotherapy for women with metastatic breast carcinoma. Cancer 88:124–131

    Article  PubMed  CAS  Google Scholar 

  5. Mavroudis D, Malamos N, Alexopoulos A et al (1999) Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: a multicenter phase II trial. Greek Breast Cancer Cooperative Group. Ann Oncol 10:211–215

    Article  PubMed  CAS  Google Scholar 

  6. Fountzilas G, Nicolaides C, Bafaloukos D et al (2000) Docetaxel and gemcitabine in anthracycline-resistant advanced breast cancer: a Hellenic Cooperative Oncology Group Phase II study. Cancer Invest 18:503–509

    Article  PubMed  CAS  Google Scholar 

  7. Seidman AD, Hudis CA, Albanell J et al (1998) Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 16:3353–3361

    PubMed  CAS  Google Scholar 

  8. Fountzilas G, Tsavdaridis D, Kalogera-Fountzila A et al (2001) Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer. A Hellenic Cooperative Oncology Group phase II study. Ann Oncol 12:1545–1551

    Article  PubMed  CAS  Google Scholar 

  9. Green MC, Buzdar AU, Smith T et al (2005) Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol 23:5983–5992

    Article  PubMed  CAS  Google Scholar 

  10. Fountzilas G, Kalofonos HP, Dafni U et al (2004) Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 15:1517–1526

    Article  PubMed  CAS  Google Scholar 

  11. Cavalli F, Beer M, Martz G et al (1983) Concurrent or sequential use of cytotoxic chemotherapy and hormone treatment in advanced breast cancer: report of the Swiss Group for Clinical Cancer Research. Br Med J (Clin Res Ed) 286:5–8

    Article  CAS  Google Scholar 

  12. Jelliffe RW (1973) Letter: Creatinine clearance: bedside estimate. Ann Intern Med 79:604–605

    PubMed  CAS  Google Scholar 

  13. Calvert AH, Newell DR, Gumbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748–1756

    PubMed  CAS  Google Scholar 

  14. Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655

    Article  PubMed  CAS  Google Scholar 

  15. Kind P (1996) The EuroQol Instrument: an index of health-related quality of life. In: Spilker B (ed) Quality of life and pharmacoeconomics in clinical trials, 2nd edn. Lippincott Raven, Philadelphia, 191:201

  16. Greiner W, Weijnen T, Nieuwenhuizen M et al (2003) A single European currency for EQ-5D health states. Results from a six-country study. Eur J Health Econ 4:222–231

    Article  PubMed  Google Scholar 

  17. Fountzilas G, Dimopoulos MA, Dafni U et al (2006) A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in advanced breast cancer (ABC). Ann Oncol 17:ix70

    Article  Google Scholar 

  18. Laird NM, Ware JH (1982) Random-effects models for longitudinal data. Biometrics 38:963–974

    Article  PubMed  CAS  Google Scholar 

  19. Efron B, Tibshirani RJ (1993) An introduction to the Bootstrap. Monographs on statistics and applied probability. Chapman and Hall/CRC, Boca Raton, pp 1–430

    Google Scholar 

  20. Moher D (1998) CONSORT: an evolving tool to help improve the quality of reports of randomized controlled trials. Consolidated standards of reporting trials. JAMA 279:1489–1491

    Article  PubMed  CAS  Google Scholar 

  21. Eniu A, Palmieri FM, Perez EA (2005) Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer. Oncologist 10:665–685

    Article  PubMed  CAS  Google Scholar 

  22. Perez EA, Vogel CL, Irwin DH et al (2001) Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol 19:4216–4223

    PubMed  CAS  Google Scholar 

  23. Seidman AD, Berry D, Cirrincione C et al (2008) Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 26:1642–1649

    Article  PubMed  CAS  Google Scholar 

  24. Robert N, Leyland-Jones B, Asmar L et al (2006) Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24:2786–2792

    Article  PubMed  CAS  Google Scholar 

  25. Pickard AS, Wilke CT, Lin HW et al (2007) Health utilities using the EQ-5D in studies of cancer. Pharmacoeconomics 25:365–384

    Article  PubMed  Google Scholar 

  26. Conner-Spady BL, Cumming C, Nabholtz JM et al (2005) A longitudinal prospective study of health-related quality of life in breast cancer patients following high-dose chemotherapy with autologous blood stem cell transplantation. Bone Marrow Transplant 36:251–259

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Ms. Irene Grimani (MSc), HeCOG Data Office, Athens for the statistical analysis, Ms. Evita Fragou and Ms. Dimitra Katsala for monitoring the study, Ms. Maria Moschoni, HeCOG Data Office, Athens for coordinating the data management, and Ms. Stella Dallidou for secretarial assistance. Most of all the investigators wish to express their gratitude to the patients and their families who had trusted us and participated in the trial.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G. Fountzilas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fountzilas, G., Dafni, U., Dimopoulos, M.A. et al. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer. Breast Cancer Res Treat 115, 87–99 (2009). https://doi.org/10.1007/s10549-008-0047-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-008-0047-9

Keywords

Navigation