Introduction. Evidence from the metastatic setting suggests that replacing conventional doxorubicin with nonpegylated liposomal doxorubicin (NPLD) for early breast cancer may maintain efficacy whilst reducing long-term cardiotoxicity, an important consideration with many patients going on to receive multiple lines of treatment. Methods. Consecutive patients with early breast cancer treated with NPLD were assessed for disease progression and changes in cardiac function according to left ventricular ejection fraction (LVEF). Results. Ninety-seven patients (median age at diagnosis 51 (32–76) years) were studied. The majority received NPLD (60？mg/m2 plus cyclophosphamide 600？mg/m2) adjuvantly (79.4%) and in sequence with a taxane (79.4%; docetaxel 75？mg/m2). 80.4% had radiotherapy and 15.5% received trastuzumab. Mean time to disease recurrence was 87.0 months (80.7–93.2 [95% confidence interval]) and 5-year disease-free survival was 86.0%. Mean LVEF values remained within the normal range of ≥55% during treatment and throughout the cardiac follow-up period (median 7 months, range 1–21 months). Use of trastuzumab and age at diagnosis did not appear to influence LVEF. Conclusion. NPLD appeared to be a well-tolerated substitute for conventional doxorubicin in patients with early breast cancer. 1. Introduction Nonpegylated liposomal doxorubicin (NPLD; Myocet, Teva UK) has potential advantages over conventional doxorubicin in the treatment of early breast cancer. Utilising a less cardiotoxic but equally effective treatment earlier in management may help to maximise therapeutic options later in the course of disease and thereby facilitate the use of multiple lines of therapy. In addition, substituting NPLD for doxorubicin as the standard anthracycline in early breast cancer may help address the growing concerns regarding the longer-term impact of treatment on cardiac function, a key survivorship issue [1, 2]. However, whilst NPLD has been extensively studied in metastatic breast cancer and is licensed in this regard [3–7], data on its use in early disease are currently scarce [8, 9]. As advances in diagnosis, management, and treatment have led to improved breast cancer survival, the issue of longer-term, therapy-related cardiotoxicity has taken on increasing importance, with patients potentially facing multiple, coincident insults to the heart [10]. Many of the available adjuvant therapies, which are increasingly used in combination or sequence, have been associated with some form of cardiotoxicity during or after therapy, whilst increasing age, comorbid
References
[1]
L. W. Jones, M. J. Haykowsky, J. J. Swartz, P. S. Douglas, and J. R. Mackey, “Early breast cancer therapy and cardiovascular injury,” Journal of the American College of Cardiology, vol. 50, no. 15, pp. 1435–1441, 2007.
[2]
A. M. Rahman, S. W. Yusuf, and M. S. Ewer, “Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation,” International Journal of Nanomedicine, vol. 2, pp. 567–583, 2007.
[3]
G. Batist, G. Ramakrishnan, C. S. Rao 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,” Journal of Clinical Oncology, vol. 19, no. 5, pp. 1444–1454, 2001.
[4]
L. Harris, G. Batist, R. Belt et al., “Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma,” Cancer, vol. 94, no. 1, pp. 25–36, 2002.
[5]
S. Chan, N. Davidson, E. Juozaityte et al., “Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer,” Annals of Oncology, vol. 15, no. 10, pp. 1527–1534, 2004.
[6]
G. Batist, L. Harris, N. Azarnia, L. W. Lee, and P. Daza-Ramirez, “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,” Anti-Cancer Drugs, vol. 17, no. 5, pp. 587–595, 2006.
P. Schmid, J. Krocker, C. Jehn et al., “Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial,” Annals of Oncology, vol. 16, no. 10, pp. 1624–1631, 2005.
[9]
A. Antón, A. Ruiz-Simon, A. Plazaola et al., “Phase II study of a 3-weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in Her2 positive (Her2+) early stage breast cancer patients (II-IIIa). GEICAM 2003-03 Study,” Cancer Research, vol. 69, supplement 2, p. 511, 2009.
[10]
British Society of Echocardiography Education Committee, “Echocardiography: Guidelines for Chamber Quantification,” http://www.bhf.org.uk/publications/view-publication.aspx?ps=1001601.
[11]
“Defining research. National Research Ethics Service. Ref: 0987,” December 2009, http://www.nres.nhs.uk/applications/is-your-project-research/.
[12]
A. Seidman, C. Hudis, M. Kathryn Pierri et al., “Cardiac dysfunction in the trastuzumab clinical trials experience,” Journal of Clinical Oncology, vol. 20, no. 5, pp. 1215–1221, 2002.
[13]
D. J. Slamon, B. Leyland-Jones, S. Shak et al., “Use of chemotherapy plus a monoclonal antibody against her2 for metastatic breast cancer that overexpresses HER2,” The New England Journal of Medicine, vol. 344, no. 11, pp. 783–792, 2001.
[14]
Clinicaltrials.gov, “Combination therapy with Myocet (doxorubicin HCl liposome for injection) in patients with HER2-positive breast cancer,” http://www.clinicaltrials.gov/ct2/show/NCT000712881.
[15]
J. Cortes, S. DiCosimo, M. A. Climent et al., “Nonpegylated liposomal doxorubicin (TLC-D99), Paclitaxel, and Trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase l/ll study,” Clinical Cancer Research, vol. 15, no. 1, pp. 307–314, 2009.
[16]
M. Venturini, C. Bighin, F. Puglisi 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, vol. 19, no. 5, pp. 333–338, 2010.
