The Safety of using Liposomal Doxorubicin in Combination with Trastuzumab for the
Treatment of HER-2 overexpressing Breast Cancer: A Systematic Review
Raksheeth Agarwal*, Oliver Emmanuel**
*Universitas Indonesia – (+62) 85777808310, raksheeth@hotmail.com
** Universitas Indonesia – (+62) 818635925, oliveremmanuel@hotmail.com
Introduction:
Breast cancer occurs in 124.8 and causes 21.9 deaths per 100,000 women every year. HER-2 is a
growth receptor, that when overexpressed can cause increased proliferation of cancer cells. Current
treatments for breast cancer include Trastuzumab and Doxorubicin, both of which are known to be
effective. However, the administration of trastuzumab and doxorubicin are associated with lethal
cardiotoxicity, and their combination has been heavily discouraged. Liposomal drug delivery is a
recent technological advance that allows a drug to be delivered to its incumbent site and reduces
systemic distribution, reducing systemic side effects. The purpose of this study is to evaluate the
safety of using liposomal doxorubicin in combination with trastuzumab in patients with HER-2
overexpressing breast cancer.
Methods:
Search engines PubMed and Google Scholar were used to systematically search for prospective trials
that assess the cardiac function in HER-2 overexpressing breast cancer patients undergoing treatment
with a combination of liposomal doxorubicin and trastuzumab. Inclusion criterias were used to filter
the abstracts and full texts in assessing the eligibility of the trials. The search was limited to trials
written in English and published in the last 10 years. Changes in left ventricle ejection fraction (LVEF)
were extracted from each study to assess cardiotoxicity in patients.
Results:
Four clinical trials were selected based on inclusion criteria. LVEF values were measured using either
Multi Gated Acquisition (MUGA) scan or echocardiography. In the studies by Cortes, et al. (2009)
and Chia, et al. (2006), the decrease of LVEF from baseline to post-treatment was 3% (from 63% to
60%). Martin, et al. (2011) reported a decrease of 3.6 % (from 63.5% to 59.9%), and Stickeler, et al.
(2009), of 3.4 % (from 66.1% to 62.7%). These values were compared to a trial conducted by Slamon,
et al. (2001) which used non liposomal doxorubicin in combination with trastuzumab.