Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials

Cancer Gene Therapy volume 24, pages 189–193 (2017)Cite this article

Subjects

Abstract

Despite benefits of systemic chemotherapy in breast cancer treatment, several patients with early-stage breast cancer will develop metastatic breast cancer (MBC). Doxorubicin is among the most active agents against MBC. However, the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product claimed to achieve these two objectives because of its different pharmacokinetic profile. The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials. A literature search in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical systems, ‘breast cancer’ and ‘doxorubicin’. Articles were evaluated according to the inclusion criteria. Reported hematological and non-hematological side effects were categorized. Out of 718 articles that were initially identified, 8 were in accordance with the inclusion criteria. We found that the most important side effects of PLD were skin toxicity and mucositis, but the proportion of patients who showed grade III and IV of these side effects was relatively low. On the other hand, the occurrence of cardiotoxicity, the most important problem with doxorubicin, was considerably reduced in patients treated with PLD. Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines, it has also new side effects. However, it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC, especially in those with risk factors for cardiac diseases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Mlineritsch B, Mayer P, Rass C, Reiter E, Russ G, Vesenmayer G et al. Phase II study of single-agent pegylated liposomal doxorubicin HCl (PLD) in metastatic breast cancer after first-line treatment failure. Onkologie 2004; 27: 441–446.

    CAS  PubMed  Google Scholar 

  2. Gebbia V, Mauceri G, Fallica G, Borsellino N, Tirrito ML, Testa A et al. Pegylated liposomal doxorubicin with vinorelbine in metastatic breast carcinoma. A phase I–II clinical investigation. Oncology 2002; 63: 23–30.

    Article  CAS  Google Scholar 

  3. Mlineritsch B, Schabel-Moser R, Andel J, Fridrik M, Moik M, Mayer P et al. Multicenter phase II study of pegylated liposomal doxorubicin in combination with vinorelbine as first-line treatment in elderly patients with metastatic breast cancer. Onkologie 2009; 32: 18–24.

    Article  CAS  Google Scholar 

  4. Alexopoulos A, Karamouzis MV, Stavrinides H, Ardavanis A, Kandilis K, Stavrakakis J et al. Phase II study of pegylated liposomal doxorubicin (Caelyx) and docetaxel as first-line treatment in metastatic breast cancer. Ann Oncol 2004; 15: 891–895.

    Article  CAS  Google Scholar 

  5. Verma S, Dent S, Chow BJ, Rayson D, Safra T . Metastatic breast cancer: the role of pegylated liposomal doxorubicin after conventional anthracyclines. Cancer Treat Rev 2008; 34: 391–406.

    Article  CAS  Google Scholar 

  6. Coleman RE, Biganzoli L, Canney P, Dirix L, Mauriac L, Chollet P et al. A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). Eur J Cancer 2006; 42: 882–887.

    Article  CAS  Google Scholar 

  7. Krishna R, Mayer LD . The use of liposomal anticancer agents to determine the roles of drug pharmacodistribution and P-glycoprotein (PGP) blockade in overcoming multidrug resistance (MDR). Anticancer Res 1999; 19: 2885–2891.

    CAS  PubMed  Google Scholar 

  8. O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 2004; 15: 440–449.

    Article  CAS  Google Scholar 

  9. Falandry C, Brain E, Bonnefoy M, Mefti F, Jovenin N, Rigal O et al. Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: final results of the DOGMES multicentre GINECO trial. Eur J Cancer 2013; 49: 2806–2814.

    Article  CAS  Google Scholar 

  10. O'Brien ME . Single-agent treatment with pegylated liposomal doxorubicin for metastatic breast cancer. Anticancer Drugs 2008; 19: 1–7.

    Article  CAS  Google Scholar 

  11. Lao J, Madani J, Puertolas T, Alvarez M, Hernandez A, Pazo-Cid R et al. Liposomal doxorubicin in the treatment of breast cancer patients: a review. J Drug Deliv 2013; 2013: 456409.

    Article  Google Scholar 

  12. Addeo R, Faiola V, Guarrasi R, Montella L, Vincenzi B, Capasso E et al. Liposomal pegylated doxorubicin plus vinorelbine combination as first-line chemotherapy for metastatic breast cancer in elderly women > or =65 years of age. Cancer Chemother Pharmacol 2008; 62: 285–292.

    Article  CAS  Google Scholar 

  13. Caraglia M, Addeo R, Costanzo R, Montella L, Faiola V, Marra M et al. Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. Cancer Chemother Pharmacol 2006; 57: 34–39.

    Article  CAS  Google Scholar 

  14. Rivera E, Valero V, Esteva FJ, Syrewicz L, Cristofanilli M, Rahman Z et al. Lack of activity of stealth liposomal doxorubicin in the treatment of patients with anthracycline-resistant breast cancer. Cancer Chemother Pharmacol 2002; 49: 299–302.

    Article  CAS  Google Scholar 

  15. Ranson MR, Carmichael J, O'Byrne K, Stewart S, Smith D, Howell A . Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. J Clin Oncol 1997; 15: 3185–3191.

    Article  CAS  Google Scholar 

  16. Al-Batran SE, Meerpohl HG, von Minckwitz G, Atmaca A, Kleeberg U, Harbeck N et al. Reduced incidence of severe palmar–plantar erythrodysesthesia and mucositis in a prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40 mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer. Oncology 2006; 70: 141–146.

    Article  CAS  Google Scholar 

  17. Al-Batran SE, Bischoff J, von Minckwitz G, Atmaca A, Kleeberg U, Meuthen I et al. The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial. Br J Cancer 2006; 94: 1615–1620.

    Article  CAS  Google Scholar 

  18. Lyass O, Uziely B, Ben-Yosef R, Tzemach D, Heshing NI, Lotem M et al. Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer 2000; 89: 1037–1047.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

All figures and tables are the authors' original work. This work is not NIH funded.

Author information

Author notes

  1. L Ansari and F Shiehzadeh: These authors contributed equally to this work.

Authors and Affiliations

  1. Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    L Ansari, F Shiehzadeh & S Nikoofal-Sahlabadi

  2. Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Z Taherzadeh

  3. Department of Medical Biotechnology, Nanotechnology Research Center, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    A A Momtazi-borojeni

  4. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    A Sahebkar

  5. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    A Sahebkar

  6. Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    S Eslami

  7. Department of Medical Informatics, University of Amsterdam, Amsterdam, The Netherlands

    S Eslami

Authors
  1. L Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Shiehzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z Taherzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Nikoofal-Sahlabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A A Momtazi-borojeni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Sahebkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Eslami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to A Sahebkar or S Eslami.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ansari, L., Shiehzadeh, F., Taherzadeh, Z. et al. The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials. Cancer Gene Ther 24, 189–193 (2017). https://doi.org/10.1038/cgt.2017.9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cgt.2017.9

This article is cited by

Search

Advanced search

Quick links