Work Productivity and Activity Impairment in Breast Cancer Patients Treated with Capecitabine

doi:10.4236/jct.2013.47142

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Journal of Cancer Therapy, 2013, 4, 1224-1227

http://dx.doi.org/10.4236/jct.2013.47142 Published Online September 2013 (http://www.scirp.org/journal/jct)

Work Productivity and Activity Impairment in Breast

Cancer Patients Treated with Capecitabine

Marco Vacante1, Giulia Malaguarnera2*, Manuela Pennisi3, Giuseppe Grosso2, Salvatore Salomone2,

Filippo Drago2, Erdogan Ozyalcin1, Vito Catania4, Alfredo Consoli4, Mariano Malaguarnera1

1Research Center “The Great Senescence”, Cannizzaro Hospital, University of Catania, Catania, Italy; 2International PhD Programme

in Neuropharmacology, University of Catania, Catania, Italy; 3Department of Neurosciences, University of Catania, Catania, Italy;

4Department of General Surgery, University of Catania, Catania, Italy.

Email: *[email protected]

Received June 11th, 2013; revised July 10th, 2013; accepted July 17th, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Although the majority of breast cancer patients are able to work, lower work ability and reduced job

retention have been reported. The aim of the present study was to evaluate the effect of chemotherapy with capecitabine

in patients with breast cancer on work productivity and daily activity. Methods: 34 patients with metastatic breast

cancer were enrolled for our study. Capecitabine was given twice daily at a cumulative dose of 2500 mg/m2 on days 1 -

14 and repeated on day 22. Work productivity was determined using the WPAI questionnaire. Results: We observed an

increase in absenteeism, presenteeism, work productivity loss and daily activity impairment after 1 cycle and 6 cycles of

therapy, but we could not find statistically different significances. Conclusions: This study provides some data indicat-

ing an association between problems in breast cancer and work. Our results confirm that capecitabine may improve

quality of life of patients with metastatic breast cancer.

Keywords: Breast Cancer; Capecitabine; Work Productivity; Absenteeism; Presenteeism

1. Introduction

Breast cancer is one of the most frequently diagnosed

cancer as well as a leading cause of cancer mortality in

women. A growing proportion of women diagnosed with

breast cancer, present with earlier disease stages. Appro-

ximately 50% of all women diagnosed with breast cancer

develop metastatic disease, and for these patients the av-

erage survival time from the time of diagnosis of metas-

tatic disease ranges from 20 to 36 months. After surgery,

the next question always is the need for adjuvant treat-

ment and also the choice of chemoterapeutic agent. The

goal of systemic therapy in early breast cancer is to era-

dicate micrometastases and reduce the risk of recurrence

and death.

Capecitabine is an innovative fluoropyrimidine carba-

mate, developed as an orally administered precursor of

5’-deoxy-5 fluorouridine [1]. Capecitabine is an effective,

well tolerated, and convenient treatment for patients with

breast cancer. Along a pathway with three enzymatic

steps, capecitabine is finally converted into the active

compound 5-FU at the site of tumor tissue, by the tumor-

associated angiogenic factor thymidine phosphorilase,

which is overexpressed in tumor cells [2]. The oral for-

mulation and the rarity of alopecia make capecitabine a

very acceptable and suitable drug, particularly for metas-

tatic disease, because it is associated with a better quality

of life than intravenous therapies [3]. Although the ma-

jority of breast cancer patients are able to work, lower

work ability and reduced job retention have been re-

ported [4,5]. The aim of the present study was to evaluate

the effect of chemotherapy with capecitabine in patients

with breast cancer on work productivity and daily activ-

ity.

2. Methods

Between January 2011 and February 2013, female pa-

tients with metastatic breast cancer that desired to con-

tinue their job were recruited for postoperative adjuvant

oral chemotherapy with capecitabine. The study protocol

was approved by the Institutional Review Board. Written

informed consents were obtained from all partecipants.

*Corresponding author.

Work Productivity and Activity Impairment in Breast Cancer Patients Treated with Capecitabine 1225

Further eligibility criteria included the following: 1) Age

30 to 50 years; 2) Eastern Cooperative Oncology Group

performance status of 0 or 1; 3) Adequate hematological

function (absolute leukocyte count 4000 to 12,000 leu-

kocytes/mm3; neutrophil count 2000 neutophils/mm3 or

more, and platelets 100,000/mm3 or more) hepatic func-

tion (transaminases 2.5 times or less the upper limit of

normal and serum bilirubin 2.0 mg/dl or less) and renal

function (serum creatinine below the upper limit of nor-

mal); 4) Ability to take oral medication. Patients were

excluded if they had any of following: history of severe

drug allergies, interstitial pneumonitis or pulmonary fi-

brosis, several pleural effusion or ascites, active infection,

diarrhea or serious uncontrolled comorbilities or medical

conditions. Patients were also excluded if they were par-

ticipating in another trial, unwilling to use effective con-

traception or had a medical condition or concomitant ill-

ness that might impair protocol compliance. Patients had

received no prior chemotherapy. Capecitabine was given

twice daily at a cumulative dose of 2500 mg/m2 on days

1 - 14 and repeated on day 22. The total daily dose was

divided into two equal amounts and given roughly 12 h

apart and within 30 min after a meal, usually breakfast

and dinner. Baseline assessment were medical history,

clinical examination, complete haematology with differ-

ential leucocyte count, clinical chemistry including co-

agulation parameters, tumour markers CA 125 and CA

19-9, chest radiography and computed tomographic scans

of the abdomen, pelvis and chest before starting treat-

ment at baseline.

2.1. Laboratory Exams

A complete routine chemistry including red cell count,

hemoglobin, white cell count, platelets, prothrombin time,

fasting plasma glucose, insulin, C-reactive protein, blood

urea nitrogen, serum creatinine, bilirubin, ALT, aspartate

aminotransferase, alkaline phosphatase, γ-glutamil trans-

peptidase, and creatin phosphokinase levels was per-

formed at every medical visit. All patients were included

in the safety and efficacy analyses. The severity of the

adverse effects was evaluated according to the National

Cancer Institute Common Toxicity Criteria (NCI-CTC)

version 2.0 [6].

2.2. WPAI (Work Productivity and Activity

Impairment)

Work productivity was determined using the WPAI ques-

tionnaire. Patients reported the number of actual hours

worked, hours missed due to chemotherapy, as well as

the effect on productivity while working and doing re-

gular activities during the past 7 days. The WPAI was

self-administered and consisted of four questions that eli-

cited employment status. Scores for abseteeism, presen-

teeism, overall work productivity loss and impairment in

regular (non work) daily activities, such as work around

the house, shopping, child care, exercising, studying,

were derived as follows: Absenteeism = hours missed/

hours missed + hours worked; Presenteeism = scale

score/10; Work productivity loss = absenteeism + (hours

worked × presenteeism); Daily activity impairment =

scale score/10. Score were transformed into percentage

with higher percentages indicating greater work impair-

ment, lower productivity and daily activity impairment

[7].

2.3. Statistical Analysis

Results are expressed as means +/− standard deviations.

Comparisons of quantitative data were made using the

Student’s t-test or Mann-Whitney test. Qualitative data

were analyzed using the chi-square test. A P value of <

0.05 was considered as indicating a statistically signifi-

cant difference. All data management and statistical cal-

culations were performed using SPSS 15.0 statistical

package (Chicago, IL).

3. Results

Patients’ characteristics at baseline are reported in Table

1. Blue collars (manual labourers) were 64% and white

collars (non manual/office labourers) were 35%. The oe-

strogen receptor status was positive in 25% of patients,

negative in 41%, unknown in 23%. 58% of patients had

one metastatic site, while 41% had two metastatic sites.

With regard to WPAI score, we observed an increase in

absenteeism, presenteeism, work productivity loss and

daily activity impairment after 1 cycle and 6 cycles of

therapy, but we could not find statistically different sig-

nificances (Table 2 ). Adverse events after 24 weeks che-

motherapy included gastrointestinal toxicity: 5 (14%) pa-

tients had nausea, 4 (11%) vomiting, 7 (20%) diarrhoea,

4 (11%) mucositis, 6 (17%) stomatitis, 2 (5%) abdominal

pain and 1 (2%) proctitis and higher rates of hand-foot

skin reactions (12 patients, 35%). 20 (58%) patients

showed fatigue (Table 3).

4. Discussion

Extensive clinical investigation has established that the

standard 3-week cycle of capecitabine prolongs the time

to disease progression, with similar or prolonged overall

survival in patients with metastatic breast cancer. The

possibility of staying at home instead of receiving treat-

ment in hospital represents an important role on decision

for many patients impacting less on quality of life and

offering greater freedom [8]. This preference has influ-

enced the adoption of oral capecitabine into the treatment

of breast cancer [9]. The goal of this study was to evalu-

ate the possible effects of chemotherapy stress on work

Work Productivity and Activity Impairment in Breast Cancer Patients Treated with Capecitabine

1226

Table 1. Patients’ characteristics at baseline.

Parameter

N 34

Age range (years) 32 - 49

Heart rate (beats per minute) 86

SBP (mmHg) 130 ± 14

DBP (mmHg) 84 ± 9

BMI (kg/m2) 26.4 ± 4.1

Histological grade

III

Unknown

3 (8%)

15 (44%)

10 (29%)

6 (17%)

Blue collars (manual labourers) 22 (64%)

White collars (non manual/office labourers) 12 (35%)

Oestrogen receptor status

Positive

Negative

Unknown

12 (35%)

14 (41%)

8 (23%)

Number of metastatic sites

20 (58%)

14 (41%)

Table 2. WPAI score in patients with breast cancer (mean ±

SD).

Baseline

After 1 cycle

treatment

After 6 cycles

treatment Follow up

Absenteeism 3.9  3.4 4.2  3.5* 4.4  3.9* 4.1  3.8*

Presenteeism 30.2  10.2 32.4  11.4* 34.1  14.1* 32.1  12.1*

Work productivity

loss 30.4  12.8 32.4  11.2* 34.8  12.5* 31.6  12.7*

Daily activity

impairment 41.8  15.1 43.6  14.5* 44.8  16.3* 42.8  15.9*

Comparison with baseline: P = NS*; P < 0.05**; P < 0.001***.

ability. The diagnosis and treatment of cancer can lead to

side effects, late effects and psychological distress that

reduce the mental and physical health. Capecitabine ad-

ministered as monotherapy is a reasonable choice when

single-agent chemotherapy is entertained as a treatment

option for metastatic breast cancer. Toxicities are gener-

ally manageable, even for more frail patients. Work is

often related to having a purpose in life, a sense of con-

tributing and a distraction [10]. In employees with breast

cancer, psychological and health-related distress is asso-

ciated with poorer outcomes such as higher work limita-

tions, higher presenteeism, and lower workplace support.

In our patients treated with capecitabine we did not ob-

serve statistically different significances in absenteeism,

presenteeism, work productivity loss and daily activity

impairment after 1 cycle and 6 cycles of therapy. Work

plays an important role in the psychological treatment for

many patients; in fact the level of satisfaction at work

was often stated as a strong motivator for social status

Table 3. Toxic effects in treated patients according to NCI-

CTC.

After 3 weeks

chemotherapy After 24 weeks

chemotherapy

Grade 1 - 2Grade 3 - 4 Grade 1 - 2Grade 3 - 4

Laboratory

Lowered

haemoglobin

Lowered leucocytes

Lowered platelets

Raised creatinine

Raised bilirubin

Gastrointestinal

Nausea

Vomiting

Diarrhoea

Mucositis

Stomatitis

Abdominal pain

Proctitis

Others

Fatigue

Anorexia

Alopecia

Hand-foot skin

reaction

and for social contacts. We think that cancer patients

should be encouraged to resume their activities as soon

as possible, especially when adverse events are few and

tolerable. Symptoms and well-being interact; the im-

provements of treatment adherence and the low toxicity

permitted our patients to resume their work again. If

work stress is becoming too high this may result in nega-

tive consequences for job performance and possibly the

development of diseases. Cancer diagnosis and treatment

are associated with frailty and vulnerability [11,12]. Pro-

ductivity loss due to absenteeism is often taken into ac-

count in economic evaluations that adopt a societal per-

spective and is measured simply by counting the number

of days off work; measuring productivity loss due to pre-

senteeism, on the other hand, is more complex. In fact,

the evaluation of presenteeism requires the estimation of

a normal productive output for a given role, after which

the impairment in productive output may be quantified

[13]. Reduction in symptoms reduces absenteeism, but its

impact on presenteeism is more uncertain [14,15]. De-

pression affects productivity differently depending on the

occupational status, with various aspects of productivity

more tipycally impaired in different professions [16]. The

most prevalent symptoms in breast cancer treated with

chemotherapy include fatigue, cognitive limitations, dis-

tress, sleep disturbance, hand-foot skin reaction. This

symptom was mostly present in blue collars, while fa-

tigue was present in both blue and white collars. The re-

sults of this study confirm that the use of highly active,

oral drugs with good tolerability is vital and may im-

Work Productivity and Activity Impairment in Breast Cancer Patients Treated with Capecitabine

1227

prove quality of life. This study provides some data in-

dicating an association between problems in breast can-

cer and work. It is unclear whether those who left the

workplace would have remained at work if the problems

related to cancer and its treatment were effectively ad-

dressed.

5. Acknowledgements

GM, GG, MiM were supported by the International PhD

programme in Neuropharmacology, University of Cata-

nia. The authors declare that they have no competing int-

erests.

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