76.9%
Stickeler, et al
16.23 Months
33.3%
50%
83.3%
4. Discussion
4.1. Analysis of Results
This systematic review shows that when trastuzumab is used together with liposomal doxorubicin, the
treatment is safe and effective. This can be seen when the results of each of the studies are compared
to the initial testing by dr. Slamon (2001). In dr. Slamon’s clinical trial, patients received trastuzumab
with non-liposomal doxorubicin. In this clinical trial, 27% of the patients experienced severe
cardiotoxicity that was life threatning.
In all of the studies, none of the patients showed clinical symptoms of cardiac toxicities or heart
failure. None of the patients in the studies of this review experienced severe or serious cardiac
morbidities, indicating that cardiac functioning was well maintained and that the combination of drug
was safe.
This is further supported by the data of the baseline LVEF and LVEF after 6 cycles in the test subjects.
The baseline LVEF values in all the test subjects over the four clinical trials were normal. The median
LVEF of the test subjects in the four trials did not decrease by much. As seen from figure 2, the
decrease in median LVEF values from baseline to after 6 cycles of treatment remained largely
conserved, with only negligible decreases. In the studies by Cortes, et al. (2009) and Chia, et al.
(2006), this decrease was by 3 % (from 63% to 60%). In the study by Martin, et al. (2011), this
decrease was by 3.6 % (from 63.5% to 59.9%). In the study by Stickeler, et al. (2009), this decrease
was by 3.4 % (from 66.1% to 62.7%). This portrays that the LVEF values did not fall significantly,
and the patients’ cardiac function was well maintained.
Even though the cardiac functions of the patients receiving this combination of drugs was maintained
well, there were some asymptomatic drops in LVEF that characterized the events as cardiotoxicity
according to pre-defined criteria by the authors. The incidence for this was 17% in the study by Cortes,
et al., 16.7% in the study by Martin, et al., 10% in the study by Chia, et al., and 19% in the study by
Stickeler et al. Nevertheless, we see that in most of these patients, the LVEF recovered to normal.
We see that t he patients in the study by Chia, et al. showed excellent cardiac tolerability to the
treatment, with only 10% experiencing pre-defined cardiotoxicity. This may be because the cut off
baseline LVEF values in this study was higher (55%), as compared to 50% in the other 3 studies
(Table 2). This suggests that the patients in the study by Chia, et al. might have had a healthier cardiac
function at the start of the study than the patients in the other three studies. This in turn suggests that
initial cardiac function may play a role in predicting possible cardiotoxicity during treatment.