International Journal of Clinical Medicine, 2011, 2, 346-351
doi:10.4236/ijcm.2011.23060 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)
Quality of Life of Patients with Metastatic Breast
Cancer Treated with Epirubicin and Docetaxel*
Jaana Korpela1, Pekka Mali1, Anne Kaljonen2, Eeva Salminen1
1Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland; 2 Turku Institute for Child and Youth
Research, University of Turku, Turku, Finland.
Received April 24th, 2011; revised May 28th, 2011; accepted June 16th, 2011.
ABSTRACT
This phase II study assessed the clinical response and short-term quality of life of patients receiving first-line chemo-
therapy with epirubicin-docetaxel combination for metastatic breast cancer. Thirty-one breast cancer patients were
treated with epirubicin (75 mg/m2 for 15 minutes) followed one hour later by a one-hour infusion of docetaxel (75
mg/m2) q3w. EORTC QLQ-C30 and EORTC QLQ-BR23 forms were filled in at baseline, and at th e second and eighth
cycle of chemotherapy. The combination of epirubicin and docetaxel provided a high degree of clinical benefit. Clinical
response was observed in 17 patients (55 %), including five (16%) complete responses and 12 (39%) partial responses.
Of responding and stable patients 23 (74%) maintained the same status for at least six months (clinical benefit). The
mean survival time was 40.8 months. Du ring the treatment the emotional fun ctioning improved and the concerns abou t
the future were relieved. Some aspects of quality of life were impaired, with slightly decreased physical and cognitive
functioning, distress related to body image and hair loss, and adverse effects of chemotherapy. Overall, the global
quality of life was maintained.
Keywords: Metastatic Breast Cancer, Chemotherapy, Epirubicin, Docetaxel, Quality of Life
1. Introduction
As metastatic breast cancer still remains essentially in-
curable, the main goals of therapy include treatment of
symptoms and maintaining the quality of life, as well as
a delay in disease progression and prolongation of over-
all survival. As women with metastatic breast cancer
have a relatively short expected survival time, the im-
pact on quality of life is an important factor to consider
when making treatment decisions. The adverse effects of
treatment should be kept as low as possible and small
gains must be weighed against the severity of adverse
effects. Collection of data from formal quality of life
instruments can broaden the parameters of benefit be-
yond response and survival, and can allow more accu-
rate determination of the supportive and ameliorative
interventions needed by the patients. Nevertheless, per-
haps due to methodological difficulties, many clinical
trials in metastatic breast cancer have been published
without quality of life data [1].
Chemotherapy is the mainstay of treatment for me-
tastatic breast cancer patients with hormone receptor-
negative disease or with hormone receptor-positive dis-
ease which h as become resis tant to en docr ine ther apy, or
is rapidly progressive and life-threatening. Anthracy-
cline- and taxane- based therapies have shown the high-
est degree of response in metastatic breast cancer. Tax-
ane-containing regimens are associated with increased
overall survival [2]. Relatively few studies have reported
the effect of the combination of anthracyclines and tax-
anes on the quality of life among women treated
first-line for metastatic breast cancer [3-8]. Even less is
known about the effects of epirubicin and docetaxel
combination on the quality of life. To our knowledge
previously only Yeo et al. have reported the effects of an
epirubicin and docetaxel combination on the quality of
life in metastatic breast cancer [9].
Previously, we have reported the efficacy, toxicity
and cost of treatment with the combination of epirubicin
and docetaxel in metastatic breast cancer [10-12]. This
report assessed the short-term quality of life outcome.
2. Methods
2.1. Patients and Treatment
Originally thirty-eight patients with metastatic breast
*Supported by the Cancer Society of South-Western Finland (JK).

Quality of Life of Patients with Metastatic Breast Cancer Treated with Epirubicin and Docetaxel347
cancer were treated with the combination of epirubicin
and docetaxel. In this report on ly the 35 Finnish-speaking
patients were included. Eligibility criteria for the epiru-
bicin-docetaxel study included written informed consent,
age 18 - 75 years, ECOG performance status <2, white
blood cell count >3000/mm3, platelet count >130,000/
mm3, and liver function <3 times the normal value. Pre-
vious adjuvant treatment with CMF (cyclophos- phamide,
methotrexate and 5-fluorouracil) or CEF (cyclo-phos-
phamide, epirubicin and 5-fluorouracil) was allowed, as
were prior hormonal therapy or radiotherapy. Exclusion
criteria included brain or leptomeningeal involvement
and active infection. The study was conducted according
to the ethical standards described in the Helsinki Decla-
ration. The protocol was approved by the Ethical Com-
mittee of Turku University Hospital and written informed
consent w as obtained f rom the pat ients.
The patients were treated with epirubicin (75 mg/m2
15-minute infusion) followed one hour later by docetaxel
(75 mg/m2, one-hour infusion) every three weeks. The
doses were based on earlier studies that have demon-
strated the applicable levels without growth factor sup-
port [13,14]. Mid -cycle co unts were taken on d ay 10 - 11.
The aim was to give eight cycles to responding/stable
patients. The starting dose of 75 mg/m2 for both epirubi-
cin and docetaxel was reduced by 25% if the patient was
hospitalized due to febrile neutropenia, required antibi-
otics, or developed prolonged neutropenia. Premedica-
tion of prednisolone (40 mg) was given orally the night
before treatment and continued b.i.d. on days 1 - 3. A
prophylactic anti-emetic was given according to routine
practice (5HT-blocker prior to chemotherapy infu sion).
2.2. Response
Response was defined according to WHO criteria after
the third cycle and at close of treatment [15]. Clinical
benefit was calculated for responding and stable patients
maintaining the same status for at least six months. The
mean follow-up time was 79.9 months.
2.3. Quality of Life Evaluations and Statistical
Analysis
Quality of life was assessed with the European Organ iza-
tion for Research and Treatment of Cancer Quality of
Life Questionnaire EORTC QLQ-C30 version +3 [16]
and the QLQ-BR23 Breast module [17]. The patients
filled in the EORTC QLQ-C30 forms at baseline, just
before the second and eighth cycle, and three months
after the last cycle. EORTC QLQ-C30 raw scores were
calculated according to guidelines, yielding a range of 0
- 100. A high score on the functiona l or global qu ality of
life scale represents a better level of functioning, and a
high score on the symptom or item scale represents more
symptoms. According to Osoba et al., a difference of 5
to 10 points on a 0 to 100 scale is considered a small
clinically significant change, a difference of 10 to 20
points a moderate change, and changes greater than 20
points would be interpreted as large changes in quality
of life [18].
The comparisons of quality of life scores at different
time points were carried out with analysis of variance
for repeated measurements. The analyses were per-
formed using the MIXED procedure (SAS system for
Windows XP version 9 .1.3 2003) which offers a sophis-
ticated tool for analysis of follow-up data with possible
missing data during follow-up (Littell R, Milliken GA,
Stroup W, Wolfinger RD. SAS® system for Mixed
Models. Cary, NC: SAS Institute, Inc, 1996). P-values
less than 0.05 were considered statistically significant.
The survival analysis was estimated using the Kaplan-
Meier technique.
3. Results
3.1. Patient Characteristics and Treatment
Patient characteristics are shown in Table 1. The mean
age was 50 years (range 35 - 72 years). The mean ECOG
performance status was 1 (range 0 - 2) before chemo-
therapy. Twenty-seven patients (87%) received all the
planned eight cycles.
3.2. Response
Clinical response was achieved by seventeen patients
(55%), including five (16%) complete responses (CR)
and twelve (39%) partial responses (PR). Twenty-three
patients (74%) showed clinical benefit, i.e. responding
and stable patients (CR, PR and NC) maintaining the
same status for at least six months (Table 2). The mean
overall survival time was 40.8 months (SD 23.8).
3.3. Quality of life
Of the 35 Finnish-speaking patients originally in the
epirubicin-docetaxel study, four patients had to be ex-
cluded: baseline data were missing for two patients, one
patient filled in the baseline questionnaire one day after
the first cycle instead of on the recommended date, and
one patient was non-evaluable for response and was
therefore excluded. Thirty-one patients filled in the
questionnaire at baseline before the first cycle, twenty-
four just before the second, and twenty-five before the
eighth cycle. Because only seven patients filled in the
questionnaire at the control visit three months after the
treatment, it was decided to leave this last visit out of the
analysis. The patients whose disease progressed (4 pa-
tients) did not fill in the questionnaires at the last cycle
as they did not attend the last visits either.
The results from the quality of life questionnaires are

Quality of Life of Patients with Metastatic Breast Cancer Treated with Epirubicin and Docetaxel
348
Table 1. Patient characteristics.
N %
Number of patients
Age (mean)
-Range
Performance status (WHO), mean
-Range
Prior treatment
-CMF
-CEF
-Antiestrogen
Postoperative radiotherapy
Number of metastatic organs
involved
-1
-2
-3
Disease sites
-Bone
-Liver
-Lungs
Receptors
-Er+/Pr+, Er+/Pr- or Er-/Pr+
-Er-/Pr-
Number of epirubicin-docetaxel
cycles
8
6-7
3-4
31
50
35 - 72
1
0 - 2
19
1
6
24
14
12
5
17
9
15
22
9
27
1
3
61
3
19
77
45
39
16
55
29
48
71
29
87
3
10
Table 2. Clinical response and clinical benefit.
Clinical response N % Stable for at least. 6 months
Complete response
Partial response
Stable disease
Progressive disease
5
12
10
4
16
39
32
13
5
9
9
Clinical benefit no./ % 23/74%
shown in Tables 3-5. Comparison of mean scores of
EORTC QLQ-C30 function scales and the global quality
of life scale at baseline, prior to the 2nd and 8th cycle are
shown in Table 3. The statistically and clinically sig-
nifica nt changes we re as follows : after the first cycle th e
emotional functioning improved a little (change of mean
by 7.7 points), the physical functioning decreased
slightly after the first cycle (8 points), and the cognitive
functioning decreased slightly as well (6.7 points). The
global quality of life remained unchanged. The mean
scores of EORTC QLQ-C30 symptom scales are shown
in Table 4. There were no both statistically and clini-
cally significant changes, although there was a trend
towards increased fatigue. Table 5 shows the com-
pare-son of mean scores of EORTC QLQ-BR23 breast
cancer items during the treatment. A few statistically
and clinically significant changes were observed. The
concerns about the future were modestly relieved
(change of 17 points), while distress related to body im-
age increased modestly (16.1 points). Systemic therapy
advers e effects, such as eye and mout h symptoms, he ad-
Table 3. Comparison of mean scores of EORTC QLQ-C30
function scales at baseline, and prior to the 2 nd and 8th cy cle.
Standard deviations are in parentheses.
Function
scales Baseline Mean (SD) Prior to 2nd cycle Mean (SD) Prior to 8th cycl e Mean (SD) P-value 1.-2. cycle
1.-8. cycle
2.-8. cycle
Physical 79.3 (27.5) 71.3 (26.9) 72.7 (21.0) 0.046*
0.14
0.96
Ro le 76.9 (15.4) 73.9 (27.4) 81.3 (23.2) 0.36
0.87
0.30
Cognitive 91.4 (15.4) 93.8 (11.8) 84.7 (19.6) 0.27
0.039*
0.0012*
Emo-
tional 71.8 (21.1) 79.5 (18.1) 78.7 (19.8) 0.0018* 0.25
0.10
Social 83.3 (24.3 ) 74.3 (25.5) 78.7 (22.8) 0.11
0.30
0.70
Global
QoL 68.1 (19.1) 64.3 (20.3) 68.6 (19.5) 0.47 0.78
0.73
Higher score means better functioning, scale 0 - 100. *statistically signifi-
cant difference.
ache and menopausal symptoms, increased significantly
(22 points) especially at the beginning of the treatment,
and similar changes could be seen throughout the treat-
ment regimen. Distress related to hair loss increased
significantly by 75 points.
4. Discussion
The combination of epirubicin and docetaxel provided a
high degree of clinical benefit with manageable adverse
effects in first-line chemotherapy of metastatic breast
cancer without compromising global quality of life dur-
ing the treatment.
During the treatment some positive effects were ob-
served in the quality of life. Anxiety about the future
decreased and emotional functioning also improved.
This finding of improved emotional functioning after the
start of the treatment is in line with previous studies as-
sessing the quality of life with anthracycline and taxane
combinations in metastatic breast cancer [3,8]. Accord-
ing to Ramirez et al., the improvement in emotional
functioning might merely reflect the fact that in a
life-threatening situation something was being done,
irrespective of what it was, and thus it could simply be
an indication of hope [19].
During the treatment, the quality of life declined due
to systemic chemotherapy adverse effects. In addition,
the quality of life also declined in terms of physical
functioning, distress related to body image, and upset

Quality of Life of Patients with Metastatic Breast Cancer Treated with Epirubicin and Docetaxel349
Table 4. Comparison of mean scores of EORTC QLQ-C30
symptom scales at baseline, and prior to the 2nd and 8th cy-
cle. Standard deviations are in parentheses.
Symptom
scales/items Baseline (SD) Prior to 2nd cycle
Mean (SD)
Prior to 8th
cycle
Mean (SD)
P-value
1.-2. cycle
1.-8. cycle
2.-8. cycle
Fatigue 24.4 (21.4) 33.3 ( 21.2) 31.5 (24.4) 0.064
0.12
0.99
Nausea and
vomiting 5.9 (16.4) 7.6 (11.0) 7.3 (21.0) 0.72 0.73
0.96
Pain 18.8 (21.4) 16.0 (18.7) 14.7 (18.8) 0.26
0.49
0.82
Dyspnea 23.0 (25.4) 20.8 (27.5) 16.0 (19.5) 0.17
0.23
0.88
Insomnia 30.1 (2 4.9) 25.0 (26.5) 30.7 (33.2) 0.31
0.94
0.31
Appetite loss 7.5 (16.6) 12.5 (16.5) 10.7 (24.9) 0.18
0.54
0.52
Constipation 6.5 (13.4) 9.7 (15.5) 6.7 (16.7) 0.31
0.98
0.33
Diarrhoea 4.3 (11.4) 11.1 (18.8) 6.7 ( 16 .7) 0.083
0.52
0.32
Financial
difficulties 12.2 (18.5) 15.3 (24.0) 12.0 (21.3) 0.39 0.99
0.43
Higher score indicates more symptoms, scale 0 - 100.
caused by hair loss, which are in line with the effect of
the doxorubicin and paclitaxel combination on the qual-
ity of life [3]. Moreover, the cognitive functioning de-
clined slightly. Subjective cognitive functioning and
objective tests measuring cognitive functioning do not
always correlate. Subjective cognitive decline often cor-
relates with anxiety, depression or fatigue [20,21].
However, true decline in cognitive functioning is possi-
ble as emerging evidence indicates that cognitive
changes can be associated with chemotherapy, at least in
an adjuvant setting [22]. The negative changes in quality
of life in this study could be observed throughout the
treatment. However, the negative changes did not ad-
versely influence the global quality of life. Nor have
other studies assessing the quality of life with other an-
thracycline and taxane combinations shown any signify-
cant change in the overall quality of life. This may re-
flect the difficulties encountered with data collection and
interpretation [2]. In addition, in the majority of metas-
tatic breast cancer studies, despite the different toxicity
Table 5. Comparison of mean scores of EORTC QLQ-BR23
breast cancer items at baseline, and prior to the 2nd and 8th
cycle. Standard deviations are in parentheses.
Functional
scales/items 1)Baseline Mean (SD) Cycle 2 Mean (SD) Cycle 8 Mean (SD) P-value 1.-2. cycle
1.-8. cycle
2.-8. cycle
Body image 68.1 (22.9) 58.3 (28.1) 52.0 (30.6) 0.044*
0.0026*
0.079
Sexual
functioning 24.4 (20.4) 22.5 (18.5) 21.7 (22.7) 0.84 0.55
0.63
Sexual
enjoyment 53.8 (21.7) 48.5 (34.5) 42.4 (26.2) 0.47 0.36
0.72
Future
perspective 24.7 (25.8) 41.7 (26.5) 36.0 (27.1) 0.0006* 0.091
0.15
Symptom
scales/ items 2)
Systemic
therapy side
effects
13.0 (7.5) 35.0 (12.1) 29.2 (15.1) <0.0001*
<0.0001*
0.067
Upset by
hair loss 25.0 (16.7) 68.1 (30.6) 100.0 (0) 0.047* 0.017*
0.15
Breast
symptoms 8.0 (8.2) 6.9 (9.1) 6.3 (9.4) 0.047* 0.27
0.56
Arm symptoms11.9 (12.4) 11.1 (13.9) 16.0 (14.7) 0.95
0.18
0.14
*statistically significant difference; 1) higher score indicates better func-
tioning; 2) higher score indicate s more symptoms.
profiles of the chemotherapeutic agents, only minor or
no differences among the different treatment groups
have been reported in terms of quality of life [23-25]. It
has been reported that physical functioning and treat-
ment toxicity explain only 16% of the variance in global
quality of life, perhaps mostly due to the psychic work
that patien ts are forc ed to ap ply to the sense of hope that
the treatment offers [26]. Therefore, it can be concluded
that treatment-related adverse effects do not usually sig-
nificantly impair the global quality of life.
Previously, Yeo et al. have assessed the quality of life
of Chinese metastatic breast cancer patients during six
cycles of an epirubicin-docetaxel combination treatment,
after which responding patients received an additional
three cycles of docetaxel [9]. They assessed the quality
of life using a linear analogue self-assessment scale on
nine indices in three major aspects: emotional, physical,
and selected symptoms. Yeo et al. reported deteriora-
tion of quality of life in all three aspects after the third
cycle of ch emotherapy, after which there appeared to be

Quality of Life of Patients with Metastatic Breast Cancer Treated with Epirubicin and Docetaxel
350
some improvement. However, the quality of life did not
return to baseline level although there was a trend to-
wards improved emotional functioning at the end of the
treatment. Our assessment was more comprehensive and
detailed using validated quality of life questionnaires.
Due to the differences in the methods, it is somewhat
difficult to compare the results between the studies. In
terms of physical functioning, our results are quite simi-
lar, but we found no statistically significant changes in
terms of pain, nausea or appetite. The results concern-
ing emotional functioning were different during the
chemotherapy. Nevertheless, in both studies, there was a
trend towards better emotional functioning at the end of
the treatment.
The major limitation of our quality of life study, in
addition to the small sample size, is the number of
missing questionnaires. The most common reasons for
missing data were progressive disease (four patients)
and administrative factors such as incomplete collection
of questionnaires. In the literature, many other authors
have shown that institutional and administrative factors
tend to be more influential than patient factors at least
until performance status deteriorates [3,27,28]. The
dropout of the patients with progressive disease is of
major concern because it distorts the results. The num-
ber of dropouts overestimates the effect of therapy on
quality of life as patients with progressive disease and
poor performance tolerated treatments poorly. Missing
data form one of the greatest methodological challenges
in cancer quality of life research [29].
In conclusion, the combination of epirubicin and do-
cetaxel showed clinical benefit among a good number of
patients in first-line chemotherapy of metastatic breast
cancer with manageable adverse effects. During the
treatment the emotional functioning improved and con-
cerns about the future were relieved. Some aspects of
quality of life were impaired, with slightly decreased
physical and cognitive functioning, distress related to
changes in body image and hair loss, and other adverse
effects of chemotherapy. However, the global quality of
life was maintained.
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