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Integrative therapy for advanced pancreatic cancer using Kampo and

western medicine: A case report
Masayuki Shimizua,b,c, Shin Takayamac,d,e,*, Akiko Kikuchic,d,e, Ryutaro Aritac,d, Rie Onoc,d,
Kota Ishizawad, Tadashi Ishiic,d,e
a
Shimizu Clinic, 5-4-50 Wakabayashi, Wakabayashi-ku, Sendai 984-0826, Japan
b
Public Interest Incorporated Foundation KENIKAI for traditional medicine library and clinic, 3-8-5, Chuoku, Ginza, Tokyo 104-0061, Japan
c
Department of Kampo Medicine, Tohoku University Hospital, 1-1 Seiryo-machi Aoba ward, Sendai 980-8574, Japan
d
Department of Education and Support for Regional Medicine, Tohoku University Hospital, 1-1 Seiryo-machi Aoba ward, Sendai 980-8574, Japan
e
Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba ward, Sendai 980-8575, Japan

A R T I C L E I N F O A B S T R A C T

Keywords: A 45-year-old male patient diagnosed as stage IVa pancreatic cancer received anti-cancer treatment with
Pancreatic cancer chemotherapy and radiotherapy. During the treatment, he complained of nausea, appetite loss, and fatigue.
Kampo medicine He received a Kampo diagnosis of qi deficiency, blood stasis, and heat with phlegm; consequently, qi supple-
Integrative therapy mentation, smoothing blood, and relieving fever were initiated using Juzentaihoto and Keppuchikuoto. After
Quality of life
this treatment, the symptoms showed remarkable improvement. However, computed tomography revealed
multiple lung nodules. We prescribed crude drugs with anti-cancer effects, including Scutellaria barbata and
Oldenlandia diffusa. These drugs led to slowed development of lung metastases that could be surgically
resected. He survived for 7 years after the advanced diagnosis without loss of quality of life. Kampo medicine
may be useful for disease control and supportive care in advanced pancreatic cancer patients.
© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
(http://creativecommons.org/licenses/by-nc-nd/4.0/)

Introduction
Advanced pancreatic cancer has a poor prognosis with the Japa-
nese National Cancer Center reporting a 5-year survival rate of as low
as 1.3%.1 The standard therapy for pancreatic cancer involves surgery
and/or chemotherapy. However, chemotherapy (e.g., fluorouracil, iri-
notecan, oxaliplatin, gemcitabine, or paclitaxel), and local radiother-
apy or surgery, have limited therapeutic effect in the advanced stage
of pancreatic cancer. Therefore, treatment for advanced pancreatic
cancer often focuses on palliative care for improving the quality of
life (QOL), including pain, nutrition, defecation, physical strength,
and emotion. An integrated treatment approach using Kampo medi-
cine (KM) could be a useful therapeutic option for patients with can-
cer who experience insufficient relief from western medicine (WM).
In 2018, The World Health Organization included a traditional
medicine module, including KM, in the published International Sta-
tistical Classification of Diseases and Related Health Problems, Ver-
sion 11.2 KM has been used for several conditions and disorders,
including cancer treatment. Moreover, the Japanese Society for Pallia-
tive Medicine has recommended the use of KM and crude drugs in
combination with WM.3 KM has been used to improve treatment-
* Corresponding author.
E-mail address: takayama@med.tonoku.ac.jp (S. Takayama).
related symptoms in patients with cancer and allow longer treatment
periods.4,5 This indicates that a multidisciplinary approach involving
active interventions and supportive/palliative care is necessary for
improving activities of daily living and QOL,6 which can result in pro-
longed survival.
Here, we described a case of advanced pancreatic cancer treated
with a combination of KM and WM and discussed the treatment con-
cept.
Ethical considerations
This case report and case series were approved by the institutional
review board of the Tohoku University Graduate School of Medicine
(Institutional Review Board No. 18,910).
Case presentation
In 2003, a 45-year-old man underwent pancreatic body and tail
resection for stage IIa pancreatic cancer. In 2004, the cancer was post-
operatively diagnosed with stage IVa because it had disseminated to
the peritoneum. Subsequently, he underwent anti-cancer treatment
that consisted gemcitabine and 50-Gy radiotherapy for 3 months
after fluorouracil administration. He presented to our medical office

https://doi.org/10.1016/j.explore.2020.07.003
1550-8307/© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
 ARTICLE IN PRESS
2 M. Shimizu et al. / Explore 00 (2020) 1 4

with treatment-related nausea, appetite loss, hair loss, and general
malaise.
Results
Clinical management and course disease in the case patient
Figure 1 presents the patient’s clinical treatment course, and
Table 1 provides details of the prescribed KM and crude drugs. Tradi-
tional medicine examination revealed that his tongue was coated
with reddish-yellow pigmentation and his pulse exhibited string and
slip. These Kampo diagnostic findings were indicative of qi deficiency
of the spleen, blood stasis, and heat with phlegm. Consequently, we
started Kampo treatment involving qi supplementation, smoothing
blood circulation, and fever relief using Juzentaihoto (JTT) and Kep-
puchikuoto combined with chemotherapy and radiotherapy. More-
over, crude preparations with known anti-cancer effects, including
Scutellaria barbata Herba and Oldenlandia diffusa Herba, were added
to the formula. After Kampo treatment, the patient was relieved from
general malaise. Furthermore, we prescribed Senpukuka-taishasekito
for nausea and other crude preparations for leukopenia and hair loss.
After the treatment, the patient reported a marked improvement in

Fig. 1. The clinical course of the 45-year old man with advanced pancreatic cancer.

Table 1
Kampo medicine and constituent medicines used to treat the 45-year-old man with advanced pancreatic cancer.

Kampo formula Crude drug Indication/application

Juzentaihoto (JTT) Astragalus Root, Cinnamon Bark, Rehmannia Root, Peony Root, Cni- For the relief of declined constitution after recovery from disease,
dium Rhizome, Atractylodes Lancea Rhizome, Angelica Root, Gin- fatigue and malaise, anorexia, perspiration during sleep, cold limbs,
seng, Poria Sclerotium, Glycyrrhiza and anemia.
Keppuchikuoto Angelica Root, Peony Root, Cnidium Rhizome, Rehmannia Root, For the relief of headache, heavy head feeling, shoulder stiffness, hot
Bupleurum Root, Glycyrrhiza, Peach Kernel, Platycodon Root, Saf- flush, and palpitation.
flower, Achyranthes Root, Immature Orange
Senpukuka-taishasekito Inula Flower, Jujube, Hematite, Glycyrrhiza, Ginseng, Pinellia Tuber, For the relief of epigastric burning, burp, nausea, vomiting, abdominal
Ginger pain, constipation or diarrhea, and weakness.
Goreisan (GRS) Alisma Rhizome, Atractylodes Lancea Rhizome, Polyporus Sclerotium, For the relief of the following symptoms of patients with oral dryness
Poria Sclerotium, Cinnamon Bark and decreased urine volume: edema, nephrosis, alcoholic hangover,
acute gastrointestinal catarrh, diarrhea, nausea, vomiting, dizziness,
water retention in the stomach, headache, uremia, heat-stroke, and
diabetes mellitus
Hedyotis diffusa Used as an anticancer, antitoxic, and diuretic agent in the treatment of
cancers, appendicitis, enteritis, hepatitis, eye diseases, contusion,
furunculosis, bleeding, etc.
Scutellaria barbata Used as an anti-inflammatory and diuretic agent with inhibitory
effects on several human cancers.
Lobelia chinensis For treating fever, lung cancer, and inflammation.
Fructus Polygoni Orientalis For treating rheumatoid arthritis, coronary heart disease, hernia, car-
buncle sore, and dilated bronchiectasis, as well as enhancing immu-
nity, antimicrobial, and osteogenic effects.
Corydalis Tuber For pain relief with the analgesic effect of Isoquinoline alkaloids.
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M. Shimizu et al. / Explore 00 (2020) 1 4
his treatment-related symptoms. Consequently, fluorouracil adminis-
tration was continued for its therapeutic effect in cancer. Computed
tomography (CT) examination conducted in 2004 revealed multiple
lung metastases. Given that there was slow lesion growth and that
he was faring very well under chemotherapy complemented with
Kampo treatment, the local nodules were surgically resected twice in
2008. In 2009, CT examination revealed multiple brain metastases,
which were removed through gamma knife radiosurgery and Gorei-
san (GRS) administered for brain edema. Radiation-induced nausea
and headache were ameliorated by GRS administration. In 2010, he
complained of pain in the left femur with bone scintigraphy revealing
bone metastases. Consequently, local radiotherapy was performed
and Corydalis Tuber was added to the Kampo formula for pain reduc-
tion. This led to decreased pain without opioid usage and the recov-
ery allowed him to surf. Treatment with both WM and KM allowed
the patient to survive for 7 years after being diagnosed with
advanced pancreatic cancer, which is noteworthy given that the life
expectancy is generally about 1-year for pancreatic cancer patients
with a similar stage of disease.
Discussion
The present case indicated that KM could be used for advanced
pancreatic cancer treatment as an integrative cancer therapy. The
patient maintained his activity of daily living. Further, he survived for
a relatively longer period compared to patients generally reported
for WM alone, which ranged as low as a 5-year survival rate of 1.3%.
Preoperatively, KM improves the patient’s physical strength and bal-
ances the immune system, which promotes early postoperative
recovery. In addition, it can prevent the side effects of chemotherapy
and/or radiotherapy, including nausea, appetite loss, and fatigue.
Consequently, cancer treatment can be optimized without loss of
QOL. Furthermore, KM can reduce cancer-related pain caused by
invasion, which results in reduced opioid usage in palliative care.
Additionally, KM may slow cancer progression of cancer and improve
the survival rate, as observed in our case.
The indications of JTT, which was used in the present case, include
relief from fatigue and malaise, anorexia, perspiration during sleep,
cold limbs, and anemia. Moreover, it is clinically effective in postop-
erative recovery of physical strength and alleviation of the adverse
effects of chemotherapy or radiotherapy. Experiments have been
conducted on the effects of JTT on cancer growth suppression. In
2000, Saiki reported that JTT prevented malignant progression and
tumor cell metastasis and described its mechanism of action.7 In
2003, Ikemoto et al. reported that JTT increased the regulatory activi-
ties of T cells by decreasing Foxp3 (+) Treg populations in patients
with advanced pancreatic cancer.8 In 2012, Ogawa et al. reported
that fluorouracil-induced myelosuppression may be improved by
coadministration with JTT.9
In the present case, some KM or crude drugs were applied in com-
bination with JTT for supportive care. GRS was used for chemother-
apy/radiotherapy-induced nausea and edema. Previous studies have
reported the underlying mechanisms of GRS. Yano et al. reported an
inhibitory effect of GRS on aquaporin 4 up regulation and cerebral
edema formation in a rat model of juvenile hypoxic-ischemic enceph-
alopathy.10 In 2018, Nakano et al. reported that GRS had a preventive
effect on brain edema after cerebral ischemic stroke through inhibi-
tion of aquaporin 4 upregulation.11 Keppuchikuoto has been used for
pain relief, including blood stasis-related headaches.12 It stimulated
IL-2 and TNF-a secretion in tumor-bearing mice and improved their
immune function, which resulted in tumor growth repression.13 Cor-
ydails Tuber, which includes isoquinoline alkaloids, is a crude drug
used for intractable pain that can be used for pain associated with
bone metastasis. Its analgesic effects are increased when combined
with Keppuchikuoto. Senpukuka-taishasekito is a well-known treat-
ment for nausea, vomiting, and epigastric burns in cases intractable
3
to antiemetic drugs.14,15 Hedyotis diffusa is used as an anticancer,
antitoxic, and diuretic agent to treat cancers, appendicitis, enteritis,
hepatitis, eye diseases, contusion, furunculosis, bleeding, etc.16 More-
over, Scutellaria barbata is widely used as an anti-inflammatory and
diuretic agent in Asia. Its extracts have growth inhibitory effects on
several human cancers, including lung cancer, digestive system can-
cers, hepatoma, breast cancer, and chorioepithelioma.17 Lobelia chi-
nensis is a herb that has been historically used to treat fever, lung
cancer, and inflammation. Its anti-inflammatory properties are corre-
lated with the inhibition of inducible nitric oxide synthase, cyclooxy-
genase-2, tumor necrosis factor-a, and interleukin-6 from the NF-kB
pathway.18 Fructus Polygoni Orientalis has a wide range of pharma-
cological applications, including treating rheumatoid arthritis, coro-
nary heart disease, hernia, carbuncle sore, and dilated bronchiectasis,
as well as enhancing immunity, antimicrobial, and osteogenic
effects.19
We selected these KM and crude drugs according to the Kampo
diagnosis and treatment strategy. The strategy involved qi and blood
supplementation; qi, blood, and water smoothing; and suppressing
inflammation termed as heat and cancer growth. Qi and blood sup-
plementation promote vital energy and physical strength during che-
motherapy/radiotherapy and allow early postoperative recovery. Qi,
blood, and water stasis have pathological effects that worsen general
fatigue, nausea, dyspnea, insomnia, and pain. Qi, blood, and water
smoothing decrease symptoms. Moreover, cachexia is caused by mal-
nutrition, inflammation, and cancer growth. Suppression of inflam-
mation and cancer growth combined with supplementation and
smoothing strategies could improve cachexia and maintain the QOL.
According to the theory of KM, we normally select HET for cases with
fatigue and appetite loss. HET has been reported to enhance concomitant
immunity against tumor development,20 restore antitumor T cell
responses by normalizing serum corticosterone, interleukin-12, and cos-
timulatory molecule expression,21 and prevent surgical stress-induced
immunosuppression by maintaining NK cell activity and inhibiting ele-
vation of stress mediators.22 It inhibits the production of proinflamma-
tory cytokines, particularly IL-6,23 enhances cisplatin-induced
apoptosis,24 inhibits cytokine-mediated apoptosis or necrosis, and result-
ing in a reduction of the gastrointestinal side effects of cancer chemo-
therapy.25 Additionally, HET was reported replenish B cells after
radiotherapy,26 reduce cancer-related fatigue, and improve the quality of
life in cancer patients.27 JTH or HET, with their anti-cancer and anti-
inflammatory effects, can be used to maintain patient’ QOL and contrib-
ute to a relatively long survival.
Conclusion
KM may be useful for disease control and supportive care in
patients with advanced pancreatic cancer.
Declaration of Competing Interests
S. T., A. K., and T. I. belong to the Department of Kampo and Inte-
grative Medicine at Tohoku University School of Medicine. The
department received a grant from Tsumura & Co., a Japanese manu-
facturer of Kampo medicine; however, this grant was used as per
Tohoku University rules. Potential conflicts of interest were
addressed by the Tohoku University Benefit Reciprocity Committee
and managed appropriately. The other authors have no additional
conflicts of interest to declare.
Funding
This study was supported by Tsumura & Co., a Japanese manufac-
turer of Kampo medicine.
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