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Complementary Therapies in Medicine (2014) xxx, xxx—xxx

Available online at www.sciencedirect.com

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journal homepage: www.elsevierhealth.com/journals/ctim

Effects of acupressure on fatigue of lung

cancer patients undergoing chemotherapy:
An experimental pilot study
Woung-Ru Tang a,∗, Wan-Jung Chen a, Chih-Teng Yu b,c,
Yue-Cune Chang d, Chuan-Mei Chen a, Chiu-Hua Wang a,
Sien-Hung Yang e,f

a
School of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan
b
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
c
School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
d
Department of Mathematics, Tamkang University, Taipei, Taiwan
e
Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
f
School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

KEYWORDS Summary
Fatigue; Background: This study explored the effects of acupressure on fatigue of lung cancer patients
Acupressure; undergoing chemotherapy.
Experimental study; Patients and methods: For this experimental study, 57 subjects were randomly assigned to
Lung cancer three groups: acupressure with essential oils (n = 17), acupressure only (n = 24), and sham acu-
pressure (n = 16). Acupoints were Hegu (LI4), Zusanli (ST36), and Sanyingjiao (SP6). All subjects
received acupressure once every morning for 5 months, with each acupoint pressed for 1 min.
Fatigue, functional status, anxiety, depression, and sleep quality were measured before initial
chemotherapy (T0), on Day 1 of third chemotherapy (T1), and on Day 1 of sixth chemother-
apy (T2). Outcome differences between groups were analyzed at T0, T1, and T2 by general
estimating equations.
Results: After controlling for baseline outcome values, age, and adherence to acupressure,
subjects who received acupressure with essential oils and acupressure had significantly less
fatigue in daily living activities and sleep better quality at T1 than subjects who received sham
acupressure. Subjects who received acupressure with essential oils had significantly better
sleep quality at T2 than the sham acupressure group. Subjects who received acupressure with
or without essential oils had greater odds of better functional status at T1 than the sham group.

∗ Corresponding author at: School of Nursing, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Taoyuan,

Taiwan. Tel.: +886 3 2118800 5331; fax: +886 3 2118433.

E-mail address: wtang@mail.cgu.edu.tw (W.-R. Tang).

http://dx.doi.org/10.1016/j.ctim.2014.05.006
0965-2299/© 2014 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
http://dx.doi.org/10.1016/j.ctim.2014.05.006
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YCTIM-1344; No. of Pages 11 ARTICLE IN PRESS
2 W.-R. Tang et al.

Conclusion: It is plausible that acupressure with or without essential oils helps lung cancer
patients undergoing chemotherapy reduce cancer-related fatigue and increase activity level.
Further study is wanted to test this hypothesis.
© 2014 Elsevier Ltd. All rights reserved.

Introduction
About 7.6 million people worldwide died from cancer in
2008, accounting for 13% of total mortality,1 with lung
cancer as the top cause of cancer death.2,3 Lung cancer
patients commonly experience fatigue; 70—96% of patients
on chemotherapy and 65—100% of patients receiving radio-
therapy report fatigue.4,5 Unfortunately, clinicians lack
effective methods for treating fatigue.5
Cancer-related fatigue (CRF) is defined as subjectively
perceived, persistent fatigue and exhaustion associated
with cancer and its treatment.6 Most Chinese people with
lung cancer use traditional Chinese medicine (TCM), e.g.,
Chinese herbal medicine, acupuncture, acupressure, and
qigong therapy, combined with western medicine therapy.7,8
Indeed, combining Chinese and western medicine ther-
apy is more effective on lung cancer patients than either
treatment alone.9 TCM not only reinforces the effects of
chemotherapy and avoids its side effects, but also enhances
patients’ quality of life.
In TCM, symptoms are believed to be caused by an imbal-
ance between Ying and Yang, which influences the operation
of qi, the energy of life, along meridians in the body to main-
tain health. When qi is blocked, illness will result in parts
related to the meridians,10 which connect with the qi of
organs at places called acupoints. The body has 365 impor-
tant acupoints on 14 major meridians.11 Each acupoint is
associated with a specific therapy.
Acupressure and acupuncture therapy are based on the
same theory and acupoints. Most studies on acupoint ther-
apy have tested the clinical effectiveness of acupuncture.
Since the 1970s over 500 randomized clinical trials (RCTs)
have examined acupuncture, with a few studies on improv-
ing cancer patients’ symptoms by acupressure.12—16 Only two
of them studied CRF.13,16 Acupressure has also been shown to
control fatigue in patients with end-stage renal disease.17,18
A 1998 systematic review of 500 acupuncture-related
RCTs concluded that ‘‘current quantity and quality of RCTs
still cannot demonstrate the effectiveness of acupunc-
ture.’’19,p.379 A similar conclusion was reached by four 2013
systematic reviews of TCM and CAM for controlling cancer
symptoms.20—23 The findings were criticized for issues with
research design, e.g., small sample size, imprecise defini-
tion of disease types, insufficient findings, and uncertain
conditions of sample selection. Of the four recent systemic
reviews, three investigated the effects of acupuncture,20—22
and one investigated the effect of all CAM modalities on
CRF.23 No reviews investigated acupressure.
Compared to acupuncture, acupressure is safe, conve-
nient, and inexpensive; with a little training, it can be
used by research personnel, medical care workers, fam-
ily members and patients themselves.12,16,24 Acupressure
achieves its effects by applying pressure to acupoints,
thus releasing neurotransmitters that transmit signals along
neurons or activate the hypothalamic-pituitary-adrenal axis
to regulate endocrine function.25,26 Another effect of
acupressure is to release brain neurotransmitters, endor-
phins, and other neurochemicals to reduce symptoms
of discomfort27—30 and alleviate stress.31 The effect of
acupressure on CRF has only been examined in can-
cer survivors, after they had finished chemotherapy.13,16
Since CRF appears most serious during chemotherapy,
immediately treating CRF will positively enhance can-
cer patients’ quality of life and treatment compliance.
Therefore, our study was designed to examine the effect
of acupressure on CRF in lung cancer patients receiving
chemotherapy.
Methods
Design
For this experimental pilot study with repeated measures,
lung cancer patients were recruited from pulmonary wards
at a medical center in northern Taiwan from July 2008 to
August 2010. This feasibility trial was implemented to help
develop a future large trial.
Setting and subjects
Lung cancer patients were included if they met these
criteria: (1) receiving conventional chemotherapy, (2) no
infection, injury and ulcers around the acupoints, (3) not
taking antidepressants or suffering from a psychiatric disor-
der, (4) >18 years old, (5) never participated in acupressure
and any fatigue-related intervention, and (6) willing to learn
acupressure and apply it at home. Patients were excluded by
these criteria: (1) pregnant, (2) lymphedema at acupressure
points, (3) hemoglobin ≤ 9 g/dL, hematocrit < 30, (4) using
steroids to treat fatigue, (5) moderate-to-severe heart fail-
ure or thyroid disorder, and (6) diagnosed with hepatitis and
its acute exacerbation.
Patients were screened by physicians in pulmonary
wards, who referred possible subjects to a research assis-
tant (RA) for assessment. Patients meeting the study criteria
and willing to participate were enrolled. Those who agreed
to participate were randomly allocated to three groups by
flipping a coin twice. If the flipped coin landed heads two
consecutive times, participants were randomized to receive
essential oils and acupressure (group A); if the coin landed
heads/tails one time, and tails/heads the second time,
participants were randomized to receive only acupressure
(group B); if the coin landed tails two consecutive times,
participants were randomized to receive sham acupressure
(group C).

Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
http://dx.doi.org/10.1016/j.ctim.2014.05.006
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Effects of acupressure on cancer-related fatigue
Figure 1 Acupoint locations.
Interventions
We chose three acupoints (Fig. 1), Hegu (LI4), Zusanli (ST36),
and Sanyingjiao (SP6), which have been related to energy
in the human body and were shown to alleviate fatigue in
cancer patients.13 Sham acupressure was applied on the
first metacarpal head, patella, and inner ankle (Fig. 1).
These three locations have no acupoints, are not related to
improving CRF, and are in the same dermatome region as our
three acupoints, as suggested for experimental acupressure
studies.32,33
Acupressure skills include pointing, pressing, kneading
and pushing. Pointing is finding the acupoint. Pressing is
applying enough pressure to release the flow of qi (Groups
A and B only), which the patient experiences as a dull
ache, tingling, and soreness.16 Kneading is rotating the finger
around the acupoint to stimulate the curing effect. Push-
ing is pushing the thumb from the acupoint to the limb
extremity to relax the patient’s muscles and enhance blood
circulation.34
Acupressure was implemented by two RAs who were
nursing graduate students. Both were trained in acu-
point identification and acupressure skills by qualified TCM
practitioners, who repeatedly confirmed accuracy of imple-
mentation.
All participants received six cycles of traditional
chemotherapy lasting about 5 months. During the first
chemotherapy, participants were hospitalized for 4 days. On
Day 1, an RA responsible for acupressure taught patients
how to self-administer acupressure. Patients received a
researcher-designed handbook (including a colored acupoint
map and acupressure methods), and their learning effec-
tiveness was confirmed by asking them to repeat what they
were taught. On Days 2—4 and in subsequent hospitalizations
for chemotherapy, one RA assisted patients in acupressure
and confirmed their accuracy. Instruction was enhanced
for older and less educated patients (approximately 20%)
and repeated until patients could implement acupressure
accurately. After discharge, patients self-administered acu-
pressure once daily at home.
Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
http://dx.doi.org/10.1016/j.ctim.2014.05.006
3
Participants started receiving the intervention on Day 1
of chemotherapy. Hence, the acupressure dosage was one
application per day at the specified acupoints every morning
for 5 months. As acupoints are symmetrically distributed,
acupressure was applied on both sides of the body with each
acupoint pressed in rotation for 1 min. Thus, participants
spent 6 min doing acupressure.
The acupoints and time of acupressure were based on
two studies on acupressure therapy for CRF.13,16 In one study
10 acupoints were used, and each acupoint received acu-
pressure for 3 min.16 In our study, we minimized the number
of acupoints and acupressure time because middle-aged and
elderly people in Taiwan are less well educated than their
western counterparts. After discussion with a senior clinical
TCM practitioner, we adopted the approach of the second
study,13 i.e., three acupoints and 1 min of acupressure per
acupoint.
Group A received acupressure with essential oils. This
5% essential oil compound containing extracts of fir nee-
dle, Scotch pine, tea tree, sandalwood, peppermint, and
cinnamon leaf was approved by the Therapeutic Goods
Administration of Australia as effective in reducing physi-
cal and psychological fatigue and improving immunity.35 Two
drops of essential oils were used for acupressure every time:
one drop for the three acupoints on one side of the body, and
one drop for three acupoints on the other side.
Measures
Fatigue, functional status, anxiety and depression, and sleep
quality were assessed by validated Chinese versions of the
Tang Fatigue Rating Scale (TFRS),36 Eastern Cooperative
Oncology Group Performance Status Rating (ECOG-PSR),37,38
Hospital Anxiety and Depression Scale (HADS),39,40 and Pitts-
burgh Sleep Quality Index (PSQI),41 respectively.
Tang fatigue rating scale
The 37-item TFRS has three subscales: physical functions
(15 items), psychological aspects (12 items), and daily
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4 W.-R. Tang et al.
living activities (10 items).36 Items are rated on a 1—10
point scale; higher scores indicate higher fatigue levels.
The TFRS had excellent internal consistency (Cronbach’s
alphas = 0.96—0.97) in patients with chronic heart failure36
and lung cancer,42 as well as good convergent and construct
validities.36,42 In this study, the TFRS had internal consis-
tency (Cronbach’s alpha) of 0.97.
Eastern cooperative oncology group performance status
rating
The ECOG-PSR has been widely used in Europe to measure
cancer patients’ functional status.43 The single-item ECOG-
PSR is rated on a 5-point scale from 0 (fully active) to 4
(complete reliance on others for care). Higher scores (≥2)
indicate poorer functional status.44 ECOG-PSR validity was
demonstrated by high correlation with Karnofsky’s index of
performance status (r = 0.87).43 Since the ECOG-PSR has only
one item, its internal consistency reliability cannot be deter-
mined.
Hospital anxiety and depression scale
The 14-item HADS45 was used to measure anxiety and
depression. Responses to items are rated on a 4-point scale
from 0 (not at all) to 3 (definitely),46 with each subscale
score ranging from 0 to 21 points. Higher scores indicate
higher levels of anxiety/depression. The HADS showed very
good reliability and validity in cancer patients.47 In this
study, the anxiety and depression subscales had internal con-
sistencies (Cronbach’s alphas) of 0.86 and 0.81, respectively.
Pittsburgh sleep quality index
The 19-item PSQI48 measures sleep quality and quantity in
the past month. Items are rated on a 4-point scale from 0
to 3. For cancer populations, total scores >8 indicate poor
sleep quality, and those ≤8 indicate good sleep quality.49,50
Acupressure daily log
A researcher-designed acupressure daily log was used by
subjects to record whether they implemented acupressure
and to rate six items (fatigue, anxiety, depression, pain,
activity status, and sleep quality) on visual analog scales.
Log entries were used to assess subjects’ acupressure adher-
ence.
Data collection
Data were collected at three times: one day before partic-
ipants received their first chemotherapy (T0), Day 1 of the
third chemotherapy (T1), and Day 1 of the sixth chemother-
apy (T2). To avoid bias, different personnel were responsible
for randomization, for implementing/teaching acupres-
sure, and for collecting data. To maintain a double-blind
design, data collectors and patients were unaware of group
assignment. However, personnel who implemented/taught
acupressure had to know patients’ group assignment.
Thirty minutes after acupressure was applied, the data
collector collected questionnaire data on patient wards.
Questionnaires were self-completed by literate patients. For
illiterate patients, the researcher read each questionnaire
item and recorded patients’ answers.
Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
http://dx.doi.org/10.1016/j.ctim.2014.05.006
Analysis
Data were coded and entered into SPSS (v.18). Baseline
differences among the three groups were compared by
Fisher’s exact test and one-way ANOVA. Post hoc com-
parisons were made using Tukey’s HSD post hoc test. To
compare group differences in outcome variables over the
study period, we used the generalized estimating equation
(GEE) method to account for within-subjects’ dependency
due to repeated measurements and allow variation in case
number at each time.51 Because the current GEE model does
not offer information on the working correlate matrix for
calculating effect size, we estimated sample size before
the study to ensure that power was sufficient to ver-
ify research hypotheses. Sample size was estimated as
described52 using repeated-measures ANOVA in G power
3.0.10, with power = 0.8, type 2 error ˛ = 0.05, and effect
size 2 = 0.40 based on a similar study.13 The estimated sam-
ple size was 45 (15 per group).
Ethical considerations
This study was approved by the Chang Gung Medical Cen-
ter Institutional Review Board (97-2422B). After an RA fully
informed participants, they signed consent. To protect par-
ticipants’ privacy, all data were encoded. Patients were
informed that participating or not would not affect their
medical services at the medical center.
Results
Subjects’ characteristics
Among the 83 patients who met the study criteria, 26
refused to participate due to feeling too ill (n = 17), ques-
tionnaires too long (n = 7), or emotional distress (n = 2). The
remaining 57 lung cancer patients were randomized to three
groups: group A (n = 17) received acupressure with essential
oils, group B (n = 24) received only acupressure, and group C
(n = 16) received sham acupressure. Of the 57 subjects who
started this study, 12 dropped out, leaving 45 subjects who
completed data collection (Fig. 2).
For participants’ baseline characteristics, see Table 1.
Most participants were diagnosed with Stage IV non-small
cell lung cancer. Subjects’ characteristics did not differ sig-
nificantly among groups except for age, which was treated
as a confounding variable and controlled in GEE analysis
of follow-up data. Dropouts and completers did not dif-
fer significantly in demographic and disease severity data
(p > 0.05).
Baseline fatigue, psychological status, and sleep
quality
Baseline scores for fatigue, psychological status, and sleep
quality did not differ significantly by ANOVA across the three
groups (p > 0.05, Table 2), suggesting that the major out-
come variables were homogeneous across groups before
intervention. However, these outcome measures had quite
large SDs, possibly contributing to outcomes not differing
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Effects of acupressure on cancer-related fatigue 5

Eligible patients (N=83)

Refused to participate (n=26)

Reasons:
Too ill to participate (n=17)
Questionnaires too long (n=7)
Emotional distress (n=2)

Participants (n=57)

Randomization

Group A (n=17) Group B (n=24) Group C (n=16)

T0
Acupressure/oils Acupressure only Sham acupressure

Non-completers (n=2) Non-completers (n=8) Non-completers (n=2)

Reasons: Reasons: Reasons:
Death (n=1) Death (n=4) Death (n=1) T1
Treatment change Treatment change Refused to continue
(n=1) (n=3) study (n=1)
Transfer to other
hospital (n=1)

Included in analysis Included in analysis Included in analysis

(n=17) (n=24) (n=16) T2
(15 completed study) (16 completed study) (14 completed study)

Figure 2 CONSORT diagram.

significantly among groups. Thus, baseline values of out-
come measures were controlled in GEE analyses.
Effects of acupressure on fatigue levels across
chemotherapy cycles
Adherence rates to acupressure (number of times acupres-
sure was performed/number of times acupressure should
have been performed) differed significantly for groups A,
B, and C (93.0, 91.9, and 77.3%, respectively, p < 0.001).
Hence, age, baseline outcome values, and adherence to acu-
pressure were controlled in GEE analyses, and differences
among participants’ fatigue levels (TFRS total and subscale
scores) were compared by group and time. The results of GEE
multiple linear regression models (with AR(1) as the working
correlation matrix) are shown in Table 3.
The adjusted total TFRS scores of group A changed less
from T0 to T1 and T2 than group C by 21.90 (p = 0.44) and
20.74 (p = 0.57), respectively, but these differences were
not significant (Table 3). Likewise, the adjusted total TFRS
scores of group B changed less from T0 to T1 and T2 than
group C by 27.65 (p = 0.26) and 17.66 (p = 0.59), respectively,
but not significantly. However, among the adjusted TFRS sub-
scale scores, only subscale scores for fatigue in daily activity
of groups A and B at T1 were significantly lower than those
of group C by 25.15 (p = 0.02) and 20.03 (p = 0.04), respec-
tively. The three groups’ adjusted fatigue subscale scores
for daily activity at T2 and for physical and psychological
dimensions at T1 and T2 did not differ significantly.
Effects of acupressure on sleep quality across
chemotherapy cycles
For group A at T1, the adjusted PSQI score changed signifi-
cantly less than that of group C by 3.00 (p = 0.048). For group
B at T2, the mean PSQI changed significantly less than that
of group C by 2.25 (p = 0.040). At other times the sleep qual-
ity of groups A and B improved, but not significantly more
than that of group C (Table 3).

Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
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Table 1 Baseline demographic and treatment characteristics by group (n = 57).

Variable Group A, n = 17 Group B, n = 24 Group C, n = 16 p

n (%) n (%) n (%)

Age (years), mean ± SD 53.9 ± 9.8 54.8 ± 9.5 66.1 ± 8.0 <0.001a
Gender
Male 9 (52.9) 12 (50.0) 12 (75.0) 0.260
Female 8 (47.1) 12 (50.0) 4 (25.0)
Education
≤Sixth grade 8 (47.1) 6 (25.0) 10 (62.5) 0.188
Junior high or high school 7 (41.2) 15 (62.5) 5 (31.3)
≥College 2 (11.8) 3 (12.5) 1 (6.3)
Marital status
Single 1 (5.9) 2 (8.3) 1 (6.3) 0.335
Married 12 (70.6) 19 (79.2) 13 (81.3)
Divorced 1 (5.9) 3 (12.5) 0 (0.0)
Widow/Widower 3 (17.6) 0 (0.0) 2 (12.5)
Type of lung cancer
NSCLC 16 (94.1) 20 (83.3) 11 (68.8) 0.158
SCLC 1 (5.9) 4 (16.7) 5 (31.3)
Cancer stage
I 1 (5.9) 1 (4.2) 2 (12.5) 0.844
II 1 (5.9) 1 (4.2) 0 (0.0)
III 3 (17.6) 7 (29.2) 3 (18.8)
IV 12 (70.6) 15 (62.5) 11 (68.8)
Chemotherapy
Gemcitabine 10 (58.8) 6 (28.6) 4 (25.0) 0.427
Gemcitabine + Cisplatin + Taxotere 2 (11.8) 3 (14.3) 1 (6.3)
Gemcitabine + Cisplatin + Navelbine 2 (11.8) 3 (14.3) 2 (12.5)
Gemcitabine + Cisplatin 0 (0.0) 1 (4.2) 0 (0.0)
Gemcitabine + Cisplatin + Taxol 1 (5.9) 4 (19.0) 6 (37.5)
Other 2 (11.8) 4 (19.0) 3 (18.8)
Hb (g/dl), mean ± SD 13.0 ± 1.5 12.0 ± 2.3 13.1 ± 1.5 0.133
Hct (%), mean ± SD 39.6 ± 3.7 36.5 ± 6.2 39.6 ± 4.1 0.073
ECOG-PSR
0 8 (47.1) 11 (45.8) 6 (37.5) 0.902
1 3 (17.6) 7 (29.2) 3 (18.8)
2 4 (23.5) 4 (16.7) 4 (25.0)
3 2 (11.8) 2 (8.3) 3 (18.8)
NSCLC: non-small cell lung cancer; SLCL: small cell lung cancer; ECOG-PSR: Eastern Cooperative Oncology Group Performance Status
Rating.
a Post hoc comparison was conducted using Tukey’s HSD post hoc test on age. The mean age of Group C (sham acupressure) was

significantly older than that of Group A (essential oils and acupressure) (p = 0.001) and Group B (pure acupressure) (p = 0.001).

Acupressure effects on psychological symptoms
across chemotherapy cycles
Although groups A and B had lower anxiety and depression
(HADS scores) at T1 and T2 than group C, these differences
were not significant (Table 3).
Acupressure effects on functional status across
chemotherapy cycles
Logistic regression by GEE analysis was used to investigate
the multivariate adjusted odds ratios for ECOG-PSR scores
that were significant in univariate analysis (Table 4). Groups
A and B had 0.113 (p = 0.037) and 0.011 (p = 0.007) times
greater odds ratios, respectively of better functional status
(ECOG-PSR ≥ 2) than group C at T1. However, at T2 the odds
ratios for functional status did not differ significantly among
groups (Table 4).
Discussion
Our results show that, after controlling for confounding
variables, lung cancer patients who received acupressure
with essential oils (group A) or acupressure only (group
B) had smaller increases in total TFRS scores at the third
(T1) and sixth (T2) chemotherapy than participants who
received sham acupressure (group C). These results suggest

Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
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Effects of acupressure on cancer-related fatigue 7

Table 2 Outcome measure scores by treatment group and measurement time.

Outcome measure Measurement time Group A n = 17 Group B n = 24 Group C n = 16

TFRS total T0 113.5 ± 61.9 130.2 ± 62.1 150.5 ± 63.2

T1 125.9 ± 67.6 115.4 ± 68.1 187.9 ± 74.4
T2 122.9 ± 73.3 135.1 ± 74.1 175.7 ± 75.0
TFRS-Physiology T0 51.5 ± 26.3 57.3 ± 28.0 61.6 ± 26.6
T1 58.2 ± 30.1 48.3 ± 28.6 68.3 ± 29.4
T2 56.8 ± 37.0 54.3 ± 29.8 66.4 ± 28.8
TFRS-Psychology T0 33.9 ± 23.3 42.8 ± 25.0 45.2 ± 23.4
T1 38.7 ± 23.7 37.3 ± 22.5 54.7 ± 22.8
T2 42.2 ± 28.4 45.0 ± 25.0 52.6 ± 24.3
TFRS-Activity T0 29.1 ± 20.3 30.0 ± 18.0 43.8 ± 27.4
T1 29.1 ± 18.3 29.8 ± 19.3 64.9 ± 31.2
T2 23.9 ± 14.3 35.8 ± 22.8 56.7 ± 33.7
HADS-Anxiety T0 6.24 ± 4.38 7.21 ± 3.58 6.94 ± 3.62
T1 5.20 ± 3.19 4.00 ± 3.39 8.00 ± 6.08
T2 5.27 ± 5.05 5.07 ± 3.71 7.18 ± 4.56
HADS-Depression T0 7.41 ± 4.40 7.29 ± 4.39 8.75 ± 3.80
T1 6.80 ± 3.47 7.19 ± 4.00 11.14 ± 5.83
T2 6.07 ± 4.68 7.93 ± 2.84 9.73 ± 5.52
PSQI T0 8.82 ± 4.63 9.63 ± 4.72 9.44 ± 3.76
T1 7.93 ± 4.06 8.31 ± 5.67 10.71 ± 5.41
T2 7.53 ± 4.29 7.47 ± 4.88 10.09 ± 4.76
T0: Before initial chemotherapy; T1: Day 1 of third chemotherapy; T2: Day 1 of sixth chemotherapy; TFRS: Tang Fatigue Rating Scale;
HADS: Hospital Anxiety and Depression Scale; PSQI: Pittsburgh Sleep Quality Index.

that fatigue levels of the experimental groups (A and B)
increased only slightly during chemotherapy, but this differ-
ence was not significant. This lack of significance was likely
due to the small sample and low study power. However, fur-
ther analysis showed that lung cancer patients undergoing
chemotherapy and receiving acupressure with or without
essential oils had significantly less fatigue related to daily
living activities (TFRS subscale scores) and better functional
status (ECOG-PSR scores) than their counterparts receiving
sham acupressure.
For this study, we used three major acupoints associ-
ated with channels of the large intestine (Hegu), stomach
(Zusanli), and three Ying channels: spleen, liver, and kid-
ney (Sanyingjiao). Pressing these three acupoints not only
benefits partial symptoms, but also enhances the balance
between Ying and Yang, as well as flow of qi and circulation.
Thus, acupressure at these points assists subjects with their
physical functions.
Our study is unique in combining acupressure and essen-
tial oils, which have been shown to benefit CRF,53,54 as
one intervention group. In our clinical experience, essential
oils alleviate cancer patients’ unpleasant symptoms. How-
ever, their effectiveness on CRF has seldom been rigorously
tested. Essential oils have complex chemical elements that
can enter the body by breathing, massage or bathing to stim-
ulate endogenous endorphins. This treatment can release
stress, enhance balance between the endocrine and nervous
systems, and lower tension55 Essential oil therapy has been
shown to effectively lower CRF,53 release lower back pain
and improve activity.56,57
The added effect of essential oils on acupressure was
likely limited because GEE analysis showed no significant
difference between acupressure with and without essen-
tial oils (data not shown). However, using essential oils
with acupressure for advanced cancer patients, particularly
those with cachexia, not only contributed therapy from the
oil ingredients, but also lubricated and protected patients’
fragile skin. Future studies with larger samples and power
can probe the effectiveness of essential oils with or without
acupressure on CRF.
Acupressure with and without essential oils not only
decreased patients’ fatigue related to daily living activi-
ties and increased functional status, but also significantly
improved sleep quality (PSQI scores). These results
are consistent with reports that pressing Sanyingjiao18,58
and Zusanli18 improves sleep quality in hemodialysis
patients.18,58 In clinical practice, Zusanli is pressed to
release stomach qi and treat illnesses related to the stom-
ach and intestines. Since the digestive tract is innervated
by parasympathetic nerves, enhancing parasympathetic
nerve activity will suppress sympathetic nerve activity,
relaxing patients and improving their sleep quality. Like-
wise, Sanyingjiao is pressed in clinical practice to draw
advantages from the three Ying channels (spleen, liver,
and kidney). Pressing Sanyingjiao adjusts physical energy
to Ying and suppresses the temper to improve sleep
quality59 .
Another possible explanation for our finding is that partic-
ipants who received acupressure with and without essential
oils were more active. If they could participate in social or
leisure activities, play their usual roles, and even exercise
instead of lying down all day, their nighttime sleep qual-
ity would be enhanced. Our findings are consistent with
previous arguments that treating major cancer symptoms

Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
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Table 3 Effects of acupressure on lung cancer patients’ fatigue levels (TFRS scores), psychological symptoms (HADS scores)
and sleep quality (PSQI scores).

Variable Estimate Standard error 2 p

TFRS-Total
Group × Timea
Group A × T2 −20.74 36.42 0.32 0.569
Group A × T1 −21.90 28.35 0.60 0.440
Group B × T2 −17.66 33.15 0.28 0.594
Group B × T1 −27.65 24.56 1.27 0.260
TFRS-Physiology
Group × Timea
Group A × T2 1.02 14.35 0.01 0.943
Group A × T1 0.85 12.53 0.01 0.946
Group B × T2 −2.32 11.05 0.04 0.833
Group B × T1 −3.29 11.00 0.09 0.765
TFRS-Psychology
Group × Timea
Group A × T2 4.56 12.32 0.14 0.711
Group A × T1 0.09 9.19 0.00 0.992
Group B × T2 −1.94 11.47 0.03 0.866
Group B × T1 −5.90 8.39 0.49 0.482
TFRS-Activity
Group × Timea
Group A × T2 −26.41 14.53 3.30 0.069
Group A × T1 −25.15 11.11 5.13 0.024
Group B × T2 −12.62 14.54 0.75 0.385
Group B × T1 −20.03 9.67 4.29 0.038
PSQI
Group × Timea
Group A × T2 −3.00 1.73 3.01 0.083
Group A × T1 −3.00 1.51 3.90 0.048
Group B × T2 −2.25 1.10 4.21 0.040
Group B × T1 −1.48 1.63 0.82 0.365
HADS-Anxiety
Group × Timea
Group A × T2 −1.02 2.29 0.20 0.656
Group A × T1 −0.77 1.66 0.22 0.643
Group B × T2 −1.02 1.88 0.29 0.589
Group B × T1 −1.58 1.48 1.13 0.289
HADS-Depression
Group × Timea
Group A × T2 −2.14 2.43 0.78 0.378
Group A × T1 −2.39 1.88 1.61 0.204
Group B × T2 0.87 2.04 0.18 0.671
Group B × T1 −0.10 1.76 0.01 0.955
Reference for group = group C: sham acupressure; reference for time = T0: baseline assessment.
a Group × Time: Interaction between group and time.

improves other distressful symptoms that tend to occur in
clusters.60
Until now, only two small studies showed the effective-
ness of acupressure on CRF, but the study participants were
cancer survivors who had completed chemotherapy.13,16
In contrast, our participants were undergoing chemother-
apy, when fatigue has repeatedly been found to be the
most distressing.61 Our participants were also on average
older, male, and had later stage lung cancer than those in
previous studies.13,16 Furthermore, all our participants had
lung cancer, which has a poorer prognosis (5-year survival
rate = 16%2 ) than breast cancer patients (5-year survival
rate can be >90%3 ), who were the majority in previous
studies.13,16 Lung cancer patients also have more severe
distressful symptoms (e.g., fatigue, pain and difficulty
breathing, and insomnia) than other cancer patients.62,63
Hence, lung cancer patients need an intervention they can
practice at home. Our study shows that acupressure is a
safe and simple intervention that can be applied even by
late stage lung cancer patients undergoing chemotherapy.

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cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
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Effects of acupressure on cancer-related fatigue
Table 4 Effects of acupressure on lung cancer patients’ physical function (ECOG-PSR score).
Variable Estimate Standard error
ECOG-PSR
Group × Timea
Group A × T2 −2.65 1.85
Group A × T1 −4.55 1.66
Group B × T2 −1.05 1.08
Group B × T1 −2.18 1.05
ECOG-PSR: Eastern Cooperative Oncology Group Performance Status Rating.
a Group × Time: Interaction between group and time.
b 95% CI for OR: 95% confidence interval for odds ratio, adjusted for the effects of baseline outcome values, age, and adherence to
acupressure.
Furthermore, our results show that acupressure reduces
fatigue related to daily activity and improves sleep qual-
ity of lung cancer patients. If our preliminary results can
be validated in large-scale RCTs, the use of acupressure can
be promoted in pre-chemotherapy interventions on patients
with lung cancer, thus reducing CRF during chemotherapy.
Study limitations and future directions
Despite its contributions, this study had some limitations.
First, this pilot study had a small sample (N = 57) and
lacked enough power to detect the effectiveness of acu-
pressure on CRF. More rigorous investigation of this topic
requires multi-center studies with larger samples. Sec-
ond, our sample comprised only lung cancer patients under
chemotherapy, limiting inference about the findings to all
cancer cases or patients receiving other therapies (e.g.,
surgery or radiotherapy). Thus, future studies should recruit
subjects with different cancer diagnoses and different treat-
ments to increase generalizability. Third, data were only
collected 30 minutes after acupressure was done; thus, the
response duration is unknown. In future studies, fatigue
should be assessed before and after acupressure. Fourth,
despite our efforts to maintain a double-blind study, sub-
jects who received essential oils may have guessed their
group status. This problem may be avoided in future stud-
ies by adding another sham-acupressure group with essential
oils, thus more rigorously testing the effectiveness of acu-
pressure with essential oils.
Relevance to clinical practice
Few studies have examined the effectiveness of acupressure
on cancer patients, underlining the need for more studies to
determine the effects of relevant factors, e.g., duration of
acupressure intervention, pressure technique, dosage, and
number of acupoints. Although we did not find a significant
benefit of acupressure on total fatigue, we found beneficial
effects on fatigue related to daily living activities and sleep
quality in lung cancer patients undergoing chemotherapy. It
is plausible that acupressure with or without essential oils
helps lung cancer patients undergoing chemotherapy reduce
cancer-related fatigue and increase activity level. Further
study is wanted to test this hypothesis.
Please cite this article in press as: Tang W-R, et al. Effects of acupressure on fatigue of lung can-
cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
http://dx.doi.org/10.1016/j.ctim.2014.05.006
9
95% CI for ORb Exp(B) p
(0.00, 2.68) 0.071 0.153
(0.00, 0.29) 0.011 0.007
(0.04, 2.92) 0.351 0.332
(0.02, 0.88) 0.113 0.037
Conflict of interest
The authors have declared no conflicts of interest.
Acknowledgments
This work was supported by the National Science Council in
Taiwan (grant no. NMRPD180821). Special thanks to all the
lung cancer patients who participated in this research. The
time spent with you will be a treasured experience in our
lives.
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cer patients undergoing chemotherapy: An experimental pilot study. Complement Ther Med (2014),
http://dx.doi.org/10.1016/j.ctim.2014.05.006