EJC Supplements
Volume 9, Issue 2 , Pages 11-15, October 2011

Anthracyclines in the management of metastatic breast cancer: state of the art

  • Alessandra Gennari

      Affiliations

    • Corresponding Author InformationCorresponding author. Alessandra Gennari, Division of Medical Oncology, Galliera Hospital, Mura delie Cappuccine 15, 16125 Genoa, Italy. Tel.: +39010 5634502; fax: +39 010 5634507
  • ,
  • Mauro D'Amico

Division of Medical Oncology, Galliera Hospital, Genoa, Italy

Article Outline

Abstract 

Metastatic breast cancer is a heterogeneous disease and hence it is desirable to have a variety of treatment options to meet different treatment aims in individual patients. Anthracyclines are extremely effective single agents in the treatment of metastatic breast cancer, and combination therapy with anthracycline-containing regimens significantly improves response rates and progression-free survival, compared with non-anthracycline regimens. The addition of taxanes further increases the efficacy of anthracyclines as first-line therapy. Combination therapy with trastuzumab, taxanes and anthracyclines has been shown to produce significant improvements in survival, compared with taxanes and anthracyclines alone; however, trastuzumab is associated with significant cardiotoxicity, and augments the cardiotoxicity associated with anthracycline-based regimens. New anthracycline formulations such as non-pegylated liposomal doxorubicin (NPLD) have an important role in the treatment of metastatic breast cancer. NPLD is as effective as conventional doxorubicin formulations, and can be combined with trastuzumab with acceptable toxicity. However, a number of questions remain as to how anthracycline therapy can be optimised. Ultimately, the choice of regimen will require a balance between efficacy and the impact of treatment on the patient's quality of life.

Keywords:  Anthracyclines , Chemotherapy , Doxorubicin , Drug toxicity , Liposomes , Metastatic breast cancer , Trastuzumab

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References 

  1. Fossati R , Confalonieri C , Torri V , et al.   Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women . J Clin Oncol . 1998;6:3439–3460
  2. Lord S , Ghersi D , Gattellari M , Wortley S , Wilcken N , Simes J . Antitumour antibiotic containing regimens for metastatic breast cancer . Cochrane Database Syst Rev . 2004;4: CD003367.
  3. Piccart-Gebhart MJ , Burzykowski T , Buyse M , et al.   Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer . J Clin Oncol . 2008;26:1980–1986
  4. Gennari A , Conte P , Rosso R , Orlandini C , Bruzzi P . Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies . Cancer . 2005;104:1742–1750
  5. Chia SK , Speers CH , D'Yachkova Y , et al.   The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer . Cancer . 2007;110:973–979
  6. National Comprehensive Cancer Network. Practice guidelines in oncology, v.2.2010. Breast cancer . Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed 24 September 2010.
  7. Cardoso F , Senkus-Konefka E , Fallowfield L , et al.   Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up . Ann Oncol . 2010;21(Suppl 5):v15–v19
  8. Cardoso F , Bedard PL , Winer EP , et al. , on behalf of the ESO-MBC Task Force    International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy . J Natl Cancer Inst . 2009;101:1174–1181
  9. Carrick S , Parker S , Wilcken N , et al.   Single agent versus combination chemotherapy for metastatic breast cancer . Cochrane Database Syst Rev . 2005;2: CD003372.
  10. Sledge GW , Neuberg D , Bernardo P , et al.   Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193) . J Clin Oncol . 2003;21:588–592
  11. O'Shaughnessy J , Miles D , Vukelja S , et al.   Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results . J Clin Oncol . 2002;20:2812–2823
  12. Stockler M , Wilcken N , Coates A . Chemotherapy for metastatic breast cancer - when is enough enough? . Eur J Cancer . 1997;33:2147–2148
  13. Muss HB , Case LD , Richards F , et al.   Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association . N Engl J Med . 1991;325:1342–1348
  14. Falkson G , Gelman R , Pandya K , et al.   Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment . J Clin Oncol . 1998;16:1669–1676
  15. Coates A , Gebski V , Bishop JF , et al.   Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies . N Engl J Med . 1987;317:1490–1495
  16. Harris AL , Cantwell BM , Carmichael J , et al.   Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer . Lancet . 1990;335:186–190
  17. Ejlertsen B , Pfeiffer P , Pedersen D , et al.   Decreased efficacy of cyclophosphamide, epirubicin and 5-fluorouracil in metastatic breast cancer when reducing treatment duration from 18 to 6 months . Eur J Cancer . 1993;29A:527–531
  18. Gregory RK , Powles TJ , Chang JC , Ashley S . A randomised trial of six versus twelve courses of chemotherapy in metastatic carcinoma of the breast . Eur J Cancer . 1997;33:2194–2197
  19. French Epirubicin Study Group  . Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose-intensity and duration of treatment . J Clin Oncol . 2000;18:3115–3124
  20. Nooij MA , de Haes JC , Beex LV , et al.   Continuing chemotherapy or not after the induction treatment in advanced breast cancer patients: clinical outcomes and oncologists' preferences . Eur J Cancer . 2003;39:614–621
  21. Gennari A , Amadori D , De Lena M , et al.   Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer . J Clin Oncol . 2006;24:3912–3918
  22. Mayordomo JI , Baena JM , Cirera L , et al.   Final results of a randomized trial on the role of maintenance chemotherapy with weekly paclitaxel for patients with metastatic breast cancer . J Clin Oncol . 2009;27(Suppl 15S):1001
  23. Alba E , Ruiz-Borrego M , Margelí M , et al.   Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study . Breast Cancer Res Treat . 2010;122:169–176
  24. Greenberg PA , Hortobagyi GN , Smith TL , Ziegler LD , Frye DK , Buzdar AU . Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer . J Clin Oncol . 1996;14:2197–2205
  25. Morabito A , Piccirillo MC , Monaco K , et al.   First-line chemotherapy for HER-2 negative metastatic breast cancer patients who received anthracyclines as adjuvant treatment . Oncologist . 2007;12:1288–1298
  26. Kardinal CG , Perry MC , Korzun AH , Rice MA , Ginsberg S , Wood WC . Responses to chemotherapy or chemohormonal therapy in advanced breast cancer patients treated previously with adjuvant chemotherapy. A subset analysis of CALGB Study 8081 . Cancer . 1988;61:415–419
  27. Venturini M , Bruzzi P , Del Mastro L , et al.   Effect of adjuvant chemotherapy with or without anthracyclines on the activity and efficacy of first-line cyclophosphamide, epidoxorubicin, and fluorouracil in patients with metastatic breast cancer . J Clin Oncol . 1996;14:764–773
  28. Pierga JY , Robain M , Jouve M , et al.   Response to chemotherapy is a major parameter-influencing long-term survival of metastatic breast cancer patients . Ann Oncol . 2001;12:231–237
  29. Gennari A , Bruzzi P , Orlandini C , et al.   Activity of first-line epirubicin and paclitaxel in metastatic breast cancer is independent of type of adjuvant therapy . Br J Cancer . 2004;90:962–967
  30. Batist G , Harris L , Azarnia N , Lee LW , Daza-Ramirez P . Improved anti-tumor response rate with decreased cardiotoxicity of non-pegylated liposomal doxorubicin compared with conventional doxorubicin in first-line treatment of metastatic breast cancer in patients who had received prior adjuvant doxorubicin: results of a retrospective analysis . Anticancer Drugs . 2006;17:587–595
  31. Batist G , Ramakrishnan G , Rao CS , et al.   Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer . J Clin Oncol . 2001;19:1444–1454
  32. Harris L , Batist G , Belt R , et al.   Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma . Cancer . 2002;94:25–36
  33. Slamon DJ , Leyland-Jones B , Shak S , et al.   Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 . N Engl J Med . 2001;344:783–792
  34. Gennari A , De Tursi M , Carella C , et al.   Epirubicin plus low-dose trastuzumab in HER2 positive metastatic breast cancer . Breast Cancer Res Treat . 2009;115:131–136
  35. Theodoulou M , Batist G , Campos S , Winer E , Welles L , Hudis C . Phase I study of nonpegylated liposomal doxorubicin plus trastuzumab in patients with HER2-positive breast cancer . Clin Breast Cancer . 2009;9:101–107
  36. Venturini M , Bighin C , Puglisi F , et al.   A multicentre Phase II study of non-pegylated liposomal doxorubicin in combination with trastuzumab and docetaxel as first-line therapy in metastatic breast cancer . Breast . 2010;19:333–338
  37. Livi L , Meattini I , De Luca Cardillo C , et al.   Non-pegylated liposomal doxorubicin in combination with cyclophosphamide or docetaxel as first-line therapy in metastatic breast cancer: a retrospective analysis . Tumori . 2009;95:422–426
  38. Leonard RC , Williams S , Tulpule A , Levine AM , Oliveros S . Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet) . Breast . 2009;18:218–224

PII: S1359-6349(11)70004-0

doi:10.1016/S1359-6349(11)70004-0

EJC Supplements
Volume 9, Issue 2 , Pages 11-15, October 2011