Skip to main content

Advertisement

Log in

Safety and efficacy of metronomic non-pegylated liposomal encapsulated doxorubicin in heavily pretreated advanced breast cancer patients

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Metronomic administration of the same chemotherapy agents (lower doses with closer intervals) may optimize their antiangiogenic properties. The aim of our study was to determine the efficacy and safety of a metronomic regimen based in non-pegylated liposomal doxorubicin (NPLD) in advanced breast cancer patients.

Methods

Clinical records of patients with pretreated advanced breast cancer and who were treated with the Metronomic-Cooper-type regimen consisting of weekly fixed doses of NPLD (30 mg IV) plus 5-Fluorouracil (5-FU) (500 mg IV) plus vincristine (0.25 mg IV) and daily oral cyclophosphamide (50 mg) plus prednisone (20 mg) were reviewed.

Results

In 84 pretreated patients, a tumor response was observed in 38 patients (45 %); stable disease was observed in 23 patients (27 %). Median progression-free survival (PFS) time to progression was 8.4 months and median overall survival (OS) was 21 months. The most common grade 2–3 hematologic adverse event was neutropenia, which was observed in 47 patients (56 %). Febrile neutropenia was observed in 10 patients (12 %). The most common non-hematologic adverse events were asthenia and mucositis which were observed in 60 patients (71 %) and 26 patients (31 %), respectively. Three patients (4 %) experienced an asymptomatic decline of the left ventricular ejection fraction.

Conclusions

NPLD-based metronomic regimen was effective and safe in pretreated advanced breast cancer patients. It could be considered as an appealing option to treat patients previously exposed to anthracyclines.

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

Similar content being viewed by others

References

  1. Kerbel RS (2006) Antiangiogenic therapy: a universal chemosensitization strategy for cancer? Science 312:1171–1175

    Article  PubMed  CAS  Google Scholar 

  2. Polverini PJ, Novak RF (1986) Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and bisantrene. Biochem Biophys Res Commun 140:901–907

    Article  PubMed  CAS  Google Scholar 

  3. Browder T, Butterfield CE, Kraling BM et al (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60:1878–1886

    PubMed  CAS  Google Scholar 

  4. Satti J (2009) The emerging low-dose therapy for advanced cancers. Dose Response 7:208–220

    Article  PubMed  Google Scholar 

  5. Kerbel RS, Klement G, Pritchard KI et al (2002) Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann Oncol 13:12–15

    Article  PubMed  CAS  Google Scholar 

  6. Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–2879

    Article  PubMed  CAS  Google Scholar 

  7. Rahman AM, Yusuf SW, Ewer MS (2007) Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomedicine 2:567–583

    PubMed  CAS  Google Scholar 

  8. Ewer MS, Martin FJ, Henderson C et al (2004) Cardiac safety of liposomal anthracyclines. Semin Oncol 31(6 Suppl 13):161–181

    Article  PubMed  CAS  Google Scholar 

  9. Cooper RG (1988) Adjuvant chemotherapy for breast cancer: 20 years experience using CVFMP chemotherapy. Semin Oncol 15(3 Suppl 3):29–34

    PubMed  CAS  Google Scholar 

  10. Leonard RC, Williams S, Tulpule A et al (2009) Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet). Breast 18:218–224

    Article  PubMed  CAS  Google Scholar 

  11. Antón A, Ruiz A, Plazaola A et al (2011) Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003–03 study. Ann Oncol 22:74–79

    Article  PubMed  Google Scholar 

  12. Batist G, Harris L, Azarnia N et al (2006) 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 17:587–595

    Article  PubMed  CAS  Google Scholar 

  13. Wong NS, Buckman RA, Clemons M et al (2010) Phase I/II trial of metronomic chemotherapy with daily dalteparin and cyclophosphamide, twice-weekly methotrexate, and daily prednisone as therapy for metastatic breast cancer using vascular endothelial growth factor and soluble vascular endothelial growth factor receptor levels as markers of response. J Clin Oncol 28:723–730

    Article  PubMed  CAS  Google Scholar 

  14. Pasquier E, Kavallaris M, André N (2010) Metronomic chemotherapy: new rationale for new directions. Nat Rev Clin Oncol 7:455–465

    Article  PubMed  Google Scholar 

  15. Colleoni M, Orlando L, Sanna G et al (2006) Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects. Ann Oncol 17:232–238

    Article  PubMed  CAS  Google Scholar 

  16. Bocci G, Tuccori M, Emmenegger U et al (2005) Cyclophosphamide-methotrexate ‘metronomic’ chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation. Ann Oncol 16:1243–1252

    Article  PubMed  CAS  Google Scholar 

  17. Gebbia V, Bousen H, Valerio MR (2012) Oral metronomic cyclophosphamide with and without methotrexate as palliative treatment for patients with metastatic breast carcinoma. Anticancer Res 32:529–536

    PubMed  CAS  Google Scholar 

  18. Orlando L, Cardillo A, Ghisini R et al (2006) Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic breast cancer. BMC Cancer 6:225

    Article  PubMed  Google Scholar 

  19. García-Sáenz JA, Martín M, Calles A et al (2008) Bevacizumab in combination with metronomic chemotherapy in patients with anthracycline- and taxane-refractory breast cancer. J Chemother 20:632–639

    PubMed  Google Scholar 

  20. Dellapasqua S, Bertolini F, Bagnardi V et al (2008) Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 26:4899–4905

    Article  PubMed  CAS  Google Scholar 

  21. Izumi Y, Xu L, di Tomaso E et al (2002) Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 416:279–280

    Article  PubMed  CAS  Google Scholar 

  22. Torrisi R, Balduzzi A, Ghisini R et al (2008) Tailored preoperative treatment of locally advanced triple negative (hormone receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin, and infusional fluorouracil followed by weekly paclitaxel. Cancer Chemother Pharmacol 62:667–672

    Article  PubMed  CAS  Google Scholar 

  23. Todorova VK, Kaufmann Y, Klimberg VS (2011) Increased efficacy and reduced cardiotoxicity of metronomic treatment with cyclophosphamide in rat breast cancer. Anticancer Res 31:215–220

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Teva Pharma Spain. The authors would like to acknowledge the support of TFS Develop Spain in the preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Manso.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manso, L., Valdiviezo, N., Sepúlveda, J. et al. Safety and efficacy of metronomic non-pegylated liposomal encapsulated doxorubicin in heavily pretreated advanced breast cancer patients. Clin Transl Oncol 15, 467–471 (2013). https://doi.org/10.1007/s12094-012-0954-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-012-0954-4

Keywords

Navigation