Shinshu Med J, 70⑸：275～284, 2022

A Pilot Prospective Randomized Trial with Cancer Fatigue Scale
and Juzentaihoto for Cancer-related Fatigue during
Cisplatin-based Chemotherapy for Advanced Urothelial Carcinoma
Takahisa Domen＊, Tomonori Minagawa, Hiroaki Hara
Ataru Suzuki, Teruyuki Ogawa and Osamu Ishizuka
Department of Urology, Shinshu University School of Medicine

Objectives : Chemotherapy with gemcitabine and cisplatin (GC) is a standard treatment for advanced urothelial
carcinoma. However, cancer-related fatigue (CRF) is frequently observed in patients receiving GC-chemotherapy.
This study employed the Cancer Fatigue Scale (CFS) as a novel method to monitor CRF during GC-chemotherapy
for the therapeutic effects of Juzentaihoto (JTT), a traditional Japanese (Kampo) medicine.
Methods : In this prospective single-center randomized study, 25 patients with advanced urothelial carcinoma
were randomly divided into the JTT group and the control group prior to GC-chemotherapy. The 15-item CFS
questionnaire was used to monitor CRF by providing a total score based on physical, affective, and cognitive
subscores. CFS results were monitored daily during GC-chemotherapy for 2 weeks. Physical findings andappetite were evaluated as secondary outcomes, and adverse drug reactions were recorded.
Results : Ultimately, 10 patients in the JTT group and 12 patients in the control group were analyzed. Notablepeaks in CFS total score and subscores were observed on days 6 and 10 after chemotherapy induction. Total
CFS score and the affective CFS subscore were significantly decreased in the JTT group at multiple time
points. Patients receiving JTT also showed significant suppression of appetite loss in the second half of the study.
No adverse drug effects were noted for JTT.
Conclusions : The CFS could monitor the status of CRF during GC-chemotherapy and might be a useful method
for CRF assessment. JTT may be a safe therapeutic option for CRF management in patients undergoingtreatment for advanced urothelial carcinoma. Shinshu Med J 70 : 275―284, 2022
(Received for publication January 17, 2022 ; accepted in revised form May 23, 2022)
Key words : Juzentaihoto, mitigates, cancer-related fatigueⅠdeed, approximately 70 ％ of patients who receive

Introduction

anticancer drugs report a sense of fatigue associated

The gold standard for the treatment of patientswith their treatment4）-6）. The general fatigue relatedwith advanced urothelial carcinoma (UC) is systemic

to anticancer drugs, the cancer itself, and other sur­

cisplatin-based chemotherapy. A recent regimen

rounding factors can be considered together as

for advanced UC is combination chemotherapy ofcancer-related fatigue (CRF)7）. To date, however, thegemcitabine and cisplatin (GC)1）2）. Although GC-

status of CRF induced by cisplatin-based chemo­

chemotherapy is highly effective against UC, it often

therapy remains uncertain due to the difficulty in3）

induces general fatigue as an adverse event . In­＊

Corresponding author : Takahisa Domen
Department of Urology, Shinshu University School of
Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
E-mail : sakutics@hotmail.com

No. 5, 2022

precisely evaluating it. A UC management strategy
for chemotherapy-induced CRF that includes both
treatment and monitoring is needed as well.
The Cancer Fatigue Scale (CFS) was developed by
Okuyama et al. as a scale to assess CRF8）. Its internal
275

Domen・Minagawa・Hara et al.
Table 1

Regimen of gemcitabine-cisplatin chemotherapy

Drug

Day
2

Gemcitabine 1000 mg/m

1

2

applicable to patients currently experiencing fatigue.
The validity and reliability of the scale has beentested in Germany, Taiwan and Iran9）-11）.
Juzentaihoto (JTT), a traditional Japanese (Kampo)
medicine, is prescribed for patients with deficiency
syndrome, suffering from anemia, fatigue, and an­
orexia12）. JTT also has been known to have antican­
cer effects, and in a previous study provided evidence
on that JTT may be useful for patients with cancer

8

15

○

○

○

○

○
○
○

○

○
○
○

consistency was found to be α＝0.79-0.89. It is also
considered to be simple and easy to complete and4○

Cisplatin 70 mg/m2
Dexamethasone 3.3 mg
6.6 mg
9.9 mgFosaprepitant meglumine 150 mg
Palonosetron hydrochloride 0.75 mg

3

Table 2

Constituents of JuzentaihotoConstituent medical herb

Percentage

Astragalus root
Cinnamon barkRehmannia root
Peony root
Cnidium rhizome
Atractylodes lancea rhizome
Japanese angelica root
GinsengPoria sclerotium
Glycyrrhiza

10.5
10.5
10.5
10.5
10.5
10.5
10.5
10.5
10.5
5.5

associated anorexia13）.
We evaluated the ability of CFS to monitor CRF

domized trial to assess the usefulness of the CFS toin advanced UC patients and assessed the CRF-

monitor CRF induced by GC-chemotherapy andattenuating effects of JTT during GC-chemotherapy.

evaluate the ability of JTT to attenuate CRF. The

Ⅱ
ＡMethods

Patients

protocol of this trial was approved by the Ethics
Committee of Shinshu University. Written informed
consent was obtained from all participants. Enroll­

Eligible patients with histologically confirmed ad­

ment began in January 2015, with the last patient com­vanced UC (stage Ⅲ or Ⅳ ) of the urinary bladder or

pleting the study in February 2017. Eligible patients

upper urinary tract were enrolled in this single-

were randomized at a 1 : 1 ratio into the JTT group

center study. All patients had previously been surgi­

and the control group using the Alliance Clinical Re­

cally treated for or had undergone biopsy of theirsearch Supporting System, a web-based randomizing

primary lesion, with clinical staging performed using

service.

enhanced computed tomography based on the clini­Ｃ

cal guidelines for bladder and upper urinary tract

The GC-chemotherapy regimen consisted of 1000

. Exclusion criteria included non-consent,

mg/m2 gemcitabine on days 1, 8, and 15 and 70 mg/

administration of other types of traditional Japanese

m2 cisplatin on day 2. The details of the regimen are

herbal medicines within 2 weeks before recruitment,

described in Table 1. All patients were hospitalizedinability of oral drug intake, and allergy to traditional

for at least 14 days of chemotherapy administration.1）

Japanese herbal medicines.

JTT is a dry powder extracted from 10 kinds ofＢ

herbs. The constituents of JTT are listed in Table 2.

cancer

14）
15）

Drugs

Study Design
This study was conducted as a prospective ran­

276

Patients in the JTT group received JTT at 7.5 g/day
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Cancer fatigue scale and Juzentaihoto for cancer related fatigue
Table 3

The Cancer Fatigue Scale (translated from Japanese)

This questionnaire will ask you about any sense of fatigue you may be experiencing. For each question, pleasecircle only one number you think most aptly describes your current state. Try to answer on the basis of your initial
feeling, without thinking too deeply about each question.
Right now,

No

Slightly

Somewhat

Considerably

Very much

1. Do you become tired easily?

1

2

3

4

5

2. Do you have the urge to lie down?

1

2

3

4

5

3. Do you feel exhausted?

1

2

3

4

5

4. Do you feel you have become careless?

1

2

3

4

5

5. Do you feel energetic?

1

2

3

4

5

6. Does your body feel heavy and tired?

1

2

3

4

5

7. Do you feel that you more often make errors
while speaking?

1

2

3

4

5

8. Do you feel interest in things?

1

2

3

4

5

9. Do you feel fed-up?

1

2

3

4

5

10. Do you feel you have become forgetful?

1

2

3

4

5

11. Can you concentrate on certain things?

1

2

3

4

5

12. Do you feel reluctant?

1

2

3

4

5

13. Do you feel that your thinking has become
slower?

1

2

3

4

5

14. Can you motivate yourself to do things?

1

2

3

4

5

15. Do you feel such fatigue that you don’t knowwhat to do with yourself?

1

2

3

4

5

Calculation Method
Add the item scores together for every factor.
Factor 1＝(items 1＋2＋3＋6＋9＋12＋15)－7

points(Physical subscale)

Factor 2＝20－(items 5＋8＋11＋14)

points(Affective subscale)

Factor 3＝(items 4＋7＋10＋13)－4

points(Cognitive subscale)points(Total scale score)

Add the factor scores together.

N.B. The subtractions in calculations adjust for a score of 0 as a state of no fatigue.

during the 14 days of GC-chemotherapy, The controlof the 3 CFS subscores. We monitored CFS and CFSgroup did not receive JTT or any placebo. JTT was

subscores from the baseline at day 0 (i.e., the day prioradministered orally 3 times daily before each meal

to GC-chemotherapy) to day 14. Details of the CFS

for 14 consecutive days from the beginning of GC-

and its calculation method are shown in Table 38）.

chemotherapy.

The entire study was done with the subjects underＤ

hospitalization.

ProtocolThe primary outcome was CRF status in patients

Secondary outcomes consisted of physical patient

overall and in those with and without JTT adminis­

findings, including systolic blood pressure, pulse rate,

tration as assessed by the CFS. The CFS consists ofand appetite (food intake) on days 0, 6, 10, and 14.

15 questions based on 3 subscores : physical, affective,

The amount of food intake was objectively evaluatedand cognitive. Total CFS was calculated as the sum

by medical staff (nurses and assistance nurses)

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Domen・Minagawa・Hara et al.

Fig. 1 Participant flow diagram. Enrolled patients were randomly assigned to the JTT group or thecontrol group. JTT, Juzentaihoto ; CFS, Cancer Fatigue Scale.

at every meal on day 0 and at 6, 10, and 14 days

analyzed in the 10 patients who received JTT. The

after the induction of GC-chemotherapy, with 100 ％baseline characteristics of the enrolled patients aredefined as full intake of the total amount of served

presented in Table 4. There were no remarkable

meals for the day. The occurrence and severity ofdifferences in clinical variables between the groups.

adverse drug reactions to JTT administration were

The major primary cancer was bladder (68 ％), fol­also recorded throughout the treatment period. Blood

lowed next by ureter (23 ％) and renal pelvis (9 ％).

examinations were performed on days 0, 7 and 14.

Eighteen patients (82 ％) had distant metastasis.

Ｅ

Ｂ

Statistical analysis

Primary outcome

The baseline for all measurements was set as the

The CRF status of all participants during GC-chemo­

day prior to starting GC-chemotherapy (day 0). One-

therapy is shown in Fig. 2. Total CFS score wasway repeated measures ANOVA was used to evalu­

significantly increased over baseline from day 2

ate the change from baseline in all participants andto day 14. CFS peaks were observed on days 6 andemployed to assess differences between the groups.

10, both of which exhibited significant differences

All analyses were performed using the Excel Statis­

over day 0 (p＜0.01 and p＝0.01, respectively) (Fig.

tical Program File ystat2006.xls (Igakutosho Shup­

2A). The first peak on day 6 was 5 days after thepan, Tokyo, Japan). A p-value of ＜ 0.05 was consid­

first gemcitabine administration and 4 days after

ered statistically significant.

cisplatin administration. The second peak on day 10

Ⅲ
Ａ

Results

Patients

was 2 days after the second gemcitabine administra­tion. Similar tendencies were witnessed in the CFS
subscores (Fig. 2B-D), especially the physical CFS

Twenty-five eligible patients were randomly as­

subscore, which appeared to be the primary contrib­

signed to the JTT group (n＝12) or the control grouputor to the total CFS score. The physical CFS sub­(n＝13). In the JTT group, 1 patient refused to con­score was significantly increased over baseline at all

tinue taking the drug due to its taste. One patient intime points. The affective CFS subscore was signifi­

each group withdrew from the study because of dif­cantly higher on days 6 and 10 only. The cognitive

ficulty completing the CFS. Ultimately, the data of 22

CFS subscore was significantly increased on days 4,

patients (10 in the JTT group and 12 in the control

6, 7, 8, 10, and 12 of GC-chemotherapy.

group) were analyzed as depicted in Fig. 1. The

Comparisons of CFS results between the JTT

primary and secondary endpoints were analyzed ingroup and the control group are displayed in Fig. 3.

the 22 patients who completed the study. Safety was

Total CFS on days 1, 2, 3, 10, 11, 13, and 14 was sig­

278

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Cancer fatigue scale and Juzentaihoto for cancer related fatigue

Table 4Characteristics of enrolled patients(n＝22)Total

JTT group(n＝10)

Control group(n＝12)

p71.6(63-83)

71.6(64-78)

71.7(63-83)

0.33

11
11

5
5

6
6

0.51

22.6(19.8-27.7)

22.9(20.1-27.7)

22.4(19.8-26.6)

0.17

0
1

13
9

7
3

6
6

0.18

Bladder
Renal pelvis
Ureter

15
2
5

5
1
4

10
1
1

0.11

Ⅲ
Ⅳ

4
18

3
7

1
11

0.12

10
12

5
5

5
7

0.35

1
21

0
10

1
11

0.16

Age, years
Sex
Male
FemaleBody mass index, kg/m2
Performance status

Primary cancer

Clinical stage

Surgery for primary site
Yes
No
Antidepressive/antianxiety agent
Yes
No

Fig. 2 Course of CFS during GC-chemotherapy for the overall cohort. Changes in total CFS score (A),physical CFS subscore (B), affective CFS subscore (C), and cognitive CFS subscore (D) are
shown. Statistical differences between CFS scores and baseline were determined using one-way
repeated measures ANOVA. ＊ : p＜0.05, ＊＊ : p＜0.01. CFS, Cancer Fatigue Scale.

No. 5, 2022

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Domen・Minagawa・Hara et al.

Fig. 3 Comparisons of the JTT group and the control group for changes in total CFS score (A), physical
CFS subscore (B), affective CFS subscore (C), and cognitive CFS subscore (D). Total CFS andaffective CFS subscore are significantly lower in the JTT group than in the control group on day
10. Statistical differences between the groups were determined using one-way repeated measures
ANOVA. ＊ : p＜0.05, ＊＊ : p＜0.01. CFS, Cancer Fatigue Scale ; JTT, Juzentaihoto.

nificantly attenuated in the JTT group as comparedⅣwith the control group (Fig. 3A). No remarkable

Discussion

differences were detected between the groups forThis investigation is the first to demonstrate thethe physical or cognitive CFS subscores, although theeffects of JTT in attenuating CRF as monitored byaffective CFS subscore was significantly attenuated

the CFS during GC-chemotherapy for advanced UC.

in the JTT group from day 9 to day 13 (Fig. 3B-D).

Based on CFS findings, JTT appeared to mitigate

Ｃoverall CRF and affective stress and could attenuate

Secondary outcomes
There were no remarkable differences for systolica loss in appetite without any serious adverse drug

blood pressure or pulse rate throughout GC-chemo­

reactions. The combination of the CFS and JTT may

therapy in patients overall (Fig. 4A, B). In con­represent a novel management strategy for cancer-

trast, appetite was significantly decreased on days

related fatigue.

6, 10, and 14 (Fig. 4C). In group comparisons, appe­

CRF is one of the most frequent symptoms in pa­

tite loss on days 6, 10, and 14 was significantly

tients with malignant tumors, with reported rates ofattenuated in the JTT group (p＝0.017, 0.011, and78-96 ％7）16）17）. CRF is defined as a distressing, per­0.016, respectively). No significant differences weresistent, and subjective sense of physical, emotional,

noted for systolic blood pressure or pulse rate (Fig.

and/or cognitive tiredness or exhaustion related to4D-F). Compared with the control group, no serious

cancer or cancer treatment that is not proportional

adverse events or laboratory data differences wereto recent activity and interferes with usual function­

detected in the JTT group apart from the common

ing18）. The disorder was found to adversely influenceside effects of GC-chemotherapy, such as bone mar­daily life in over half of malignant cancer patients18）.

row suppression.

Therefore, CRF associated with malignant tumors is
a serious clinical problem worldwide.
Passik et al. reported that cancer patients often fail280

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Cancer fatigue scale and Juzentaihoto for cancer related fatigue

Fig. 4 Course of physical findings during GC-chemotherapy for the overall cohort. Changes in systolic bloodpressure (A), pulse rate (B), and appetite (C) are shown. Statistical differences between physical findings
and baseline were determined using paired t-tests. Comparisons of the JTT group and the control groupfor changes from baseline in systolic blood pressure (D), pulse rate (E), and changes in appetite (F).
Appetite is significantly better maintained by JTT. Statistical differences between the groups were
determined using one-way repeated measures ANOVA. ＊ : p＜0.05, ＊＊ : p＜0.01. JTT, Juzentaihoto.

to communicate with their oncologists about fatigue19）.

CRF. We previously reported on the usefulness of

Although the most common evaluation method for

the CFS to monitor CRF during enzaltamide admin­

CRF among malignant tumor patients is the Common

istration in patients with castration-resistant pros­

Terminology Criteria for Adverse Events, the test istate cancer23）. Similarly, the CFS was able to monitor

objectively evaluated by clinicians20）. Therefore, theCRF status during GC-chemotherapy in this trial.

Common Terminology Criteria for Adverse Events

GC-chemotherapy is a standard treatment option

loses effectiveness without close communication be­

for advanced UC. CRF is one of the most common

tween the clinician and patient and may become in­side effects of chemotherapy ; it not only impairs

adequate to establish clinical evidence on CRF. In thequality of life, but also diminishes physical activity,

current-day situation with no established biomark­limits treatment, and increases morbidity3）. However,ers for CRF, general fatigue can only be evaluatedthe characteristics of CRF induced by GC-chemothera­using questionnaires, such as the Brief Fatigue In­

py have not been defined. In this preliminary study

ventory and the Edmonton Evaluation System21）22）.

investigating the usefulness of the CFS to monitor

However, problems remain regarding pathogenesis,

CRF during GC-chemotherapy, the CFS could track

objective parameters, and the evaluation of quantita­

the changes in CRF throughout treatment. Physicaltive and qualitative aspects.

fatigue appeared to be a predominant factor in theDeveloped by Japanese researchers, the CFS is thetotal CFS score. Indeed, the total CFS peaks were

only self-administered questionnaire to evaluate CRF

synchronized with those of the physical CFS subscoreon a multidimensional fatigue scale of three dimen­

on days 6 and 10. This finding indicated that treat­8）

sions : physical, affective, and cognitive . Therefore,

ment of physical condition and reduction of physicalthe CFS is a simple method to obtain both quantita­

stress could be especially beneficial for managing CRF

tive and qualitative assessments of CRF, which may

during GC-chemotherapy.

provide useful information to establish treatments forNo. 5, 2022

Definitive evidence on effective treatment strate­
281

Domen・Minagawa・Hara et al.

gies for CRF is lacking. Kampo medicine, also known

This study had several limitations that must be

as traditional Japanese herbal medicine, has been

considered when interpreting the results. First, thedeveloped to treat various conditions and has gained

patients in the control group did not receive a place­

24）
25）

. The treatment concepts

bo, and the trial was conducted as open label. There­of Kampo medicine are very different from those offore, a placebo effect cannot be ruled out. Second, themodern medicine. Almost 150 Kampo formulations

number of enrolled patients was insufficient to deter­

have been approved as prescription drugs by themine the exact effect of JTT. Previous investigations

Ministry of Health, Labor and Welfare of Japan andusing the CFS are also few in number, and this is thea unique status in Japanare used clinically for the treatment of a wide vari­first trial to employ the CFS for GC-chemotherapy.

ety of diseases. Some Kampo medications can be

In this sense, the study can be regarded as explor­

used for general fatigue, including aging problems

atory and pilot research to investigate the applicabil­and frailty. Clinically, JTT is indicated for the relief

ity of the CFS and JTT. However, as we witnessed aof declined constitution during disease recovery, gen­usefulness of the CFS and a therapeutic effect oferal fatigue, malaise, anorexia, perspiration during

JTT, this trial might be acceptable as the first step

sleep, cold limbs, and anemia. JTT has also shownto demonstrate the clinical merit of JTT. A random­

effectiveness in treating various symptoms and re­ized, double-blind, placebo-controlled study contain­

storing strength in elderly people and has provening a large number of patients with advanced UC is26）

suitable for long-term administration . Regarding

required to verify the present findings. Third, no

the mechanism of JTT function, animal studies

obvious mucositis, diarrhea, and taste abnormalities

showed that the drug increased hematopoietic effects

were observed in the patients. However, these were27）

in mice . JTT could improve immunological protec­

not actively searched for. So it is possible that thetion, including cancer immunity, by increasing hema­

patients had such latent symptoms, which may have

28）
-30）

. Koyohara et al. also reported

influenced the loss of appetite. Fourth, the observa­

that JTT decreased the toxicity (mortality and renaltion period may not have been sufficient to monitor

topoietic function

31）

toxicity) of cisplatin in mice . Furthermore, several

CRF completely with regard to GC-chemotherapy.

clinical reports have described an effect of JTT

Although the changes in the CFS persisted until the

32）
-34）

, and theend of the observation period, CFS scores should

agent has been used as an adjunctive therapy for

ideally be evaluated for longer durations. Although

on hematopoiesis and anemia recovery
35）

advanced breast cancer patients . The above resultsthese limitations limit the interpretation of the study

led us to examine the suitability of JTT to manage

results, the present study is meaningful in that such

CRF in GC-chemotherapy in the present study.

pilot study results are necessary to conduct large-

We observed that JTT could attenuate total CFS

scale, rigorous study. Once the above limitations arescore during the treatment period, especially for the

resolved, the CFS and the effect of JTT on CRF in

affective CFS subscore, as well as a loss of appetite.

UC patients during GC-chemotherapy could be demon­

Thus, JTT may primarily attenuate mental duress

strated in future trials.

during chemotherapy under hospitalization in patients

In conclusion, the present pilot study showed thewith UC. Appetite may also be better maintained

CFS appeared useful for monitoring CRF during

throughout the treatment period, particularly in the

GC-chemotherapy for severe UC and JTT could be alatter half. JTT can be a supportive drug candidate

therapeutic option for attenuating CRF symptoms.

to help manage patients under chemotherapy by pro­

The combination of the CFS and JTT could poten­

moting a favorable mental and physical state without

tially serve as a novel strategy for managing CRF

serious adverse events. It was noteworthy that weduring GC-chemotherapy for UC patients.

observed no significant physical or cognitive CFS

Ⅴ

subscore alterations in spite of the statistical im­
provement in total CFS score. A larger cohort may
reveal further differences in these subscores.
282

Conflict of Interests

None.

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References
1） von der Maase H, Hansen SW, Roberts JT, et al : Gemcitabine and cisplatin versus methotrexate, vinblastine,
doxorubicin, and cisplatin in advanced or metastatic bladder cancer : results of a large, randomized, multinational,
multicenter, phase III study. J Clin Oncol 18 : 3068-3077, 2000
2） von der Maase H, Sengelov L, Roberts JT, et al : Long-term survival results of a randomized trial comparing
gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer.
J Clin Oncol 23 : 4602-4608, 2005
3） Lop A, Manfredi A, Bonura S : Fatigue in cancer patients receiving chemotherapy : an analysis of published studies.
Ann Oncol 15 : 712-720, 2004
4） Sandler A, Nemunaitis J, Denham C, et al : Phase III trial of gemcitabine plus cisplatin versus cisplatin alone inpatients with locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 18 : 122-130, 2000
5） Campos M, Hassan B, Riechelmann R, et al : Cancer-related fatigue : a practical review. Ann Oncol 22 : 1273-1279,
2011
6） Morrow G, Shelke A, Roscoe J, et al : Management of cancer-related fatigue. Cancer Invest 23 : 229-239, 2005
7） Berger A, Mooney K, Alvarez-Perez A : National Comprehensive Cancer Network. Cancer-related fatigue, version
2. 2015. J Natl Compr Canc Netw 13 : 1012-1039, 20158） Okuyama T, Akechi T, Kugaya A, et al : Development and validation of the cancer fatigue scale : a brief, threedimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manage 19 : 5-14, 2000
9） Kröz M, Zerm R, Reif M, et al : Validation of the German version of the cancer fatigue scale (CFS-D). Eur J Cancer
Care 17 : 33-41, 200810） Montazeri A, Haghighat S, Ebrahimi M : The cancer fatigue scale (CFS) : translation and validation study of the
Iranian version. Qual Life Res 14 : 2132, 200511） Shun SC, Beck S, Pett M, et al : Psychometric testing of three Chinese fatigue instruments in Taiwan. J Pain Symptom
Manage 32 : 155-167, 200612） Ministry of health. Labour and Welfare of Japan. The Japanese pharmacopoeia, 18th Edition. 2021 (Japanese).
13） Cheon C, Yoo J, Yoo S, et al : Efficacy and safety of sipjeondaebo-tang for anorexia in patients with cancer : a pilot,
randomized, double-blind, placebo-controlled trial. Evid Based Complement Alternat Med 8780325, 201714） The Japanese Urological Association. Clinical guidelines for bladder cancer 2015. Igakutosho-shuppan, Tokyo, 2015
(Japanese)
15） The Japanese Urological Association. Clinical guidelines for renal pelvic and ureteral cancer 2014. Medical-review,
Tokyo, 2014 (Japanese)
16） Portenoy R, Itri L : Cancer-related fatigue : guidelines for evaluation and management. Oncologist 4 : 1-10, 1999
17） Berger A, Abernethy A, Atkinson A : NCCN Clinical Practice Guidelines Cancer-related fatigue. J Natl Compr Canc
Netw 8 : 904-931, 201018） Stone P, Richardson A, Ream E, et al : Cancer-related fatigue : inevitable, unimportant and untreatable ? Results of amulti-centre patient survey. Cancer Fatigue Forum. Ann Oncol 11 : 971-975, 2000
19） Passik SD, Kirsh KL, Donaghy K, et al : Fatigue Coalition.Patient-related barriers to fatigue communication : initial
validation of the fatigue management barriers questionnaire. J Pain Symptom Manage 24 : 481-493, 200220） Trotti A, Colevas A, Setser A, et al : Patient-reported outcomes and the evolution of adverse event reporting inoncology. J Clin Oncol 25 : 5121-5127, 200721） Mendoza TR, Wang XS, Cleeland CS, et al : The rapid assessment of fatigue severity in cancer patients : use of thebrief fatigue inventory. Cancer 85 : 1186-1196, 199922） Hui D, Shamieh O, Paiva C : Minimal clinically important differences in the Edmonton Symptom Assessment Scale in
No. 5, 2022

283

Domen・Minagawa・Hara et al.
cancer patients : a prospective, multicenter study. Cancer 121 : 3027-3035, 201523） Minagawa T, Domen T, Suzuki T, et al : Effectiveness of Hochuekkito (Japanese herbal medicine) for general fatigue
after introduction of enzalutamide in three cases of castration-resistant prostate cancer. Nihon Hinyokika Gakkai
Zasshi 110 : 86-91, 2019［Article in Japanese］
24） Motoo Y, Seki T, Tsutani K : Traditional Japanese medicine, Kampo : its history and current status. Chin J Integr
17 : 85-87, 2011
25） Fuyuno I : Japan : Will the sun set on Kampo ? Nature 480 : 7378, 201126） Terasawa K : Kampo Japanese-Oriental Medicine Insights from Clinical Cases. K.K. Standard Mcintyre, Tokyo Japan,
199327） Hong T, Matsumoto T, Kiyohara H, et al : Enhanced production of hematopoietic growth factors through T cell
activation in Peyer’s patches by oral administration of Kampo (Japanese herbal) medicine, “Juzen-Taiho-To”.
Phytomedicine 5 : 353-360, 1998
28） Abe S, Tansho S, Ishibashi H, et al : Protective effect of oral administration of a traditional medicine, Juzen-Taiho-To,
and its components on lethal candida albicans infection in immunosuppressed mice. Immunopharmacol Immunotoxicol
20 : 421-431, 1998
29） Kiyohara H, Matsumoto T, Takemoto N, et al : Effect of oral administration of a pectic polysaccharide fraction from a
Kampo (Japanese herbal) medicine “Juzen-Taiho-To” on antibody response of mice. Planta Med 61 : 429-434, 199530） Ohnishi Y, Fujii H, Hayakawa Y, et al : Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to
inhibits liver metastasis of colon 26-L5 carcinoma cells. Jpn J Cancer Res 89 : 206-213, 199831） Kiyohara H, Matsumoto T, Komatsu Y, et al : Protective effect of oral administration of a Pectic Polysaccharide fraction
from a Kampo (Japanese herbal) medicine “Juzen-Taiho-To” on adverse effects of cis-diaminedichloroplatinum.
Planta Med 61 : 531-534, 1995
32） Kishida Y, Nishii T, Inoue T, et al : Juzentaihoto (TJ-48), a traditional Japanese herbal medicine, influences hemoglobin
recovery during preoperative autologous blood donation and after hip surgery. Int J Clini Pharmacol Ther 47 : 716-721,
200933） Nakamoto H, Mimura T, Honda N : Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)
resistant anemia in patients on hemodialysis. Hemodial Int 12 : 9-14, 200834） Sho Y, Fujisaki K, Sakashita H, et al : Orally administered Kampo medicine, Juzen-taiho-to, ameliorates anemia
during interferon plus ribavirin therapy in patients with chronic hepatitis C. J Gastroenterol 39 : 1202-1204, 2004
35） Adachi I : Supporting therapy with Shi Quan Da Bu Tang in advanced breast cancer patients. Biomedical Research
11 : 25-31, 1990

（2022. 1. 17 received ; 2022. 5. 23 accepted）

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