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Integrating Complimentary and Alternative Medicine in Form of Active Hexose Co-Related Compound (AHCC) in the Management of Head & Neck Cancer Patients

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Objectives: The Active Hexose Correlated Compound (AHCC), is produced from mushroom mycerium and rich in al-pha glucans was administered to the cancer patients along with chemotherapy to see if it is having any beneficial effects on the final outcome in terms of reducing side effects of chemotherapy, maintaining the general condition and having effect on tumor control. Methods: Twenty five patients were administered AHCC along with conventional palliative chemotherapy regimen out of which sixteen patients received paclitaxel, and cisplatinum/carboplatin, nine patients re-ceived combination of cisplatim and 5-Flurouracil. All the patients were having advance stage (T3/T4) head and neck cancers. Thirteen patients were cancer of cheek, followed by cancer of tongue (4), oro-pharyngeal cancer (6) and can-cer of naso-pharynx (2). Results: All the patients tolerated AHCC well with no added symptoms. Twenty patients re-ported that they are feeling stronger than before at the time of initiation of chemotherapy cycles. Almost all the patients reported to have better appetite after they started taking AHCC. Twelve patients who required blood transfusion before chemotherapy cycles, decrease in the rate of fall in hemoglobin was observed in these patients and only three patients required blood transfusion before subsequent chemotherapy cycles. In 22 patients definite reduction of chemotherapy side effects like nausea, vomiting, drop in total leucocytes count, loose motion/constipation etc. were observed, which reduced the hospital stay of these patients. Tumor regressed in 11 patients, 8 patients had stable disease and in rest of the patients, the disease progressed. Conclusions: AHCC up to 3 g is safe to administer and definitely helps cancer patients in reducing side effects of chemotherapeutic drugs, getting a sense of wellbeing and improved intake maintains general condition as well as prepare them to continue and tolerate further cycles in a better way.
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International Journal of Clinical Medicine, 2011, 2, 588-592
doi:10.4236/ijcm.2011.25097 Published Online November 2011 (http://www.SciRP.org/journal/ijcm)
Copyright © 2011 SciRes. IJCM
Integrating Complimentary and Alternative
Medicine in Form of Active Hexose Correlated
Compound (AHCC) in the Management of Head
& Neck Cancer Patients
Dillip Kumar Parida
1*
, Koji Wakame
2
, Taisei Nomura
3
1
Department of Radiation Oncology, North Eastern Indira Gandhi Regional Institute of Health & Medical Sciences, Shillong, India;
2
Amino up Chemical Co. Ltd., Sapporo, Japan;
3
National Institute of Biomedical Innovation, Osaka, Japan.
Email:
*
dkparida@hotmail.com
Received September 4
th
, 2011; revised October 17
th
, 2011; accepted October 26
th
, 2011.
ABSTRACT
Objectives: The Active Hexose Correlated Compound (AHCC), is produced from mushroom mycerium and rich in al-
pha glucans was administered to the cancer patients along with chemotherapy to see if it is having any beneficial effects
on the final outcome in terms of reducing side effects of chemotherapy, maintaining the general condition and having
effect on tumor control. Methods: Twenty five patients were administered AHCC along with conventional palliative
chemotherapy regimen out of which sixteen patients received paclitaxel, and cisplatinum/carboplatin, nine patients re-
ceived combination of cisplatim and 5-Flurouracil. All the patients were having advance stage (T3/T4) head and neck
cancers. Thirteen patients were cancer of cheek, followed by cancer of tongue (4), oro-pharyngeal cancer (6) and can-
cer of naso-pharynx (2). Results: All the patients tolerated AHCC well with no added symptoms. Twenty patients re-
ported that they are feeling stronger than before at the time of initiation of chemotherapy cycles. Almost all the patients
reported to have better appetite after they started taking AHCC. Twelve patients who required blood transfusion before
chemotherapy cycles, decrease in the rate of fall in hemoglobin was observed in these patients and only three patients
required blood transfusion before subsequent chemotherapy cycles. In 22 patients definite reduction of chemotherapy
side effects like nausea, vomiting, drop in total leucocytes count, loose motion/constipation etc. were observed, which
reduced the hospital stay of these patients. Tumor regressed in 11 patients, 8 patients had stable disease and in rest of
the patients, the disease progressed. Conclusions: AHCC up to 3 g is safe to administer and definitely helps cancer
patients in reducing side effects of chemotherapeutic drugs, getting a sense of wellbeing and improved intake maintains
gene
ral condition as well as prepare them to continue and tolerate further cycles in a better way.
Keywords: Head and Neck Cancer, Quality of Life, AHCC
1. Introduction
India contributes to maximum number of Tobacco Re-
lated Cancer Deaths in the world [1]. The use of tobacco
also attributes towards tuberculosis, heart diseases and
other lung conditions in addition to neoplastic diseases
[1,2]. According to the national cancer registry (http://
www.ncrpindia.org/) data, the incidence of cancer of
head and neck region is highest in male, where as cancer
of esophagus is highest in female in the state of Megha-
laya, one of the north-eastern states of India [1]. North
eastern region (NER) of India consists of eight small
states namely Assam, Arunachal Pradesh, Nagaland,
Meghalaya, Manipur, Mizoram, Tripura and Sikkim.
These states are mainly home to various tribal popula-
tions, belonging to various ethnic origins. As their domi-
cile changes, their living condition, food pattern, disease
spectrum and life span changes. Evidences show that
majority of the population inhabiting NER use tobacco in
some or other forms in addition to alcohol and supari
(arica-nut) and combined use of all these factors are re-
sponsible for initiation of Oropharyngeal, Lungs and
upper aerodigestive tract cancers. Amongst all these
NER states the incidence of tobacco related cancers
(TRC) are very high. According to the national cancer
registry programme (NCRP) data, the difference of inci-
Integrating Complimentary and Alternative Medicine in Form of Active Hexose
589
Correlated Com
pound (AHCC) in the Management of Head & Neck Cancer Patients
dence of TRC in NER is too high in comparison to rest
of
the country [1].
Majority of these patients present with an advance
stage disease, where the nutrition status of these patients
remain low. Other poor prognostic features like old age,
stage of the disease at presentation, neck node status,
presence/absence of other metastatic sites are also very
important, while considering these patients for any kind
of treatment. With above mentioned features, many times
it becomes difficult for the patients to tolerate various
forms of anticancer treatment. Consequently it becomes
very important to maintain the general condition of the
patients at an optimum level so that the patients can tol-
erate further treatment. Therefore this trial was under-
taken to see if complimentary and alternative medicine
(CAM) in form of AHCC can maintain the nutrition/
immunity at optimum level, so the cancer patients having
advance stage disease shall be able to tolerate further
treatment like chemotherapy and radiotherapy for better
tumor control. AHCC has never been tried in the man-
agement of head and neck cancer in the clinical study.
2. Materials and Methods
2.1. Cases
Twenty five patients of advance stage (T3: 13 & T4: 12)
Head & Neck Cancer Patients were enrolled in this pro-
ject. Thirteen patients were cancer of Cheek, followed by
cancer of tongue (4), oro-pharyngeal cancer (6) and can-
cer of naso-pharynx (2) (Table 1). All the patients were
either having residual or recurrent tumors subsequent to
their primary treatment. Hence, these patients were ma-
naged with palliative chemotherapy treatment.
2.2. Active Hexose Correlated Compound
(AHCC)
AHCC is an enzyme fermented extract of the mycelia of
Basidiomycetes mushroom obtained through the mush-
room (Lentinus edodes), containing a mixture of poly-
saccharides, amino acids, lipids and minerals. The final
product is obtained by hot water extraction after cultur-
ing media and then treating them with enzymes. The
predominant components of AHCC are oligosaccharides
of which major portions are alpha-glucans having an
effect on the immune system. It has been proven as a
biological response modifier in experimental animals as
well as human being. AHCC samples were provided by
Amino Up Chemical Co., Ltd., Sapporo, Japan for con-
ducting this trial.
Majority of the patient received Taxane based chemo-
therapy along with Platinum (Cispliatin/Carboplatin) (16).
The dose of chemotherapy was customized depending on
the general condition of each of the patients. Rest patients
received platinum with 5 Fluorouracil combinations.
Twelve patients also received targeted Monoclonal An-
tibody treatment in the form of epidermal growth factor
receptor (EGFR) inhibitor. Some of the patients were
heavily pre-treated with very low general condition. As
such patients with head and neck cancers present with
low general conditions because of less oral intake. Pre-
vious treatment history of the patients includes 6 patients
had undergone surgery, 12 patients had history of radio-
therapy and 16 patients had history of chemotherapy,
prior to recruitment under this AHCC trial (Table 2).
These patients acted as their own control.
All the patients were administered AHCC 3 g of dried
extract every day morning 3 days prior to the chemo-
therapy with water scheduled date and followed up to
one week post chemotherapy either with water or milk.
The reasons being maximum toxicity of the chemother-
apy drugs are observed within first one week following
administration.
Table 1. Division of patients according to primary tumor
site.
Tumor sub-site Stage No. of patients
Cheek T3N2bM0 7
T4N2bM0 6
Tongue T3N2aM0 3
T4N2cM0 1
Oro-pharynx T3N2cM0 6
Naso-pharynx T3N2cM0 2
Table 2. Treatment history.
Treatment Modality No. of Cycles/radiation dose
No. of
patients
Chemotherapy
Paclitaxel/Docetaxel + 6 - 18 16
Cisplatin/Carboplatin
5-Flurouracil + 12 - 24 09
Cisplatin/Carboplatin
Concurrent 08
Chemo-radiation
EGFR Inhibitor Cetuximab/Nimotuzumab 12
Radiotherapy
Radical radiotherapy 60 - 66 Gy 06
Post-op radiotherapy 50 Gy 06
Surgery
06
Copyright © 2011 SciRes. IJCM
Integrating Complimentary and Alternative Medicine in Form of Active Hexose
590
Correlated Com
pound (AHCC) in the Management of Head & Neck Cancer Patients
2.3. Assessment
The hematological parameters like hemogram, liver and
kidney function tests were performed before each cycle
of chemotherapy and followed 3 days after completion of
chemotherapy. CT scan was done after completion of
three cycles and two weeks after sixth cycle of chemo-
therapy to evaluate the tumor response. The patients were
given a questionnaire on the quality of life issues and
asked specific questions regarding their general feeling,
sleep pattern, social interaction etc.
3. Results
All the patients tolerated AHCC well with no added
symptoms. Twenty patients reported that they are feeling
better and stronger than before at the time of initiation of
chemotherapy cycles (Figure 1). In most of the patients,
the sleep pattern became regular than before and the pa-
tients started interacting with visitors normally than be-
fore (Table 3). Almost all the patients reported to have
better appetite after they started taking AHCC. No pa-
tients with AHCC required appetizer.
Sixteen patients who required blood transfusion before
chemotherapy cycles, decrease in the rate of fall in he-
moglobin was observed in these patients and only three
patients required blood transfusion before subsequent
chemotherapy cycles. Only 7 patients required growth
factor with AHCC compared to 12 patients without it.
Also no patients required platelet concentrate transfusion
in AHCC group compared to 3 in without AHCC. The
comparative charts are given in Figure 1. In 22 patients
definite reduction of chemotherapy side effects like nau-
sea, vomiting, loose motion/constipation etc. were ob-
served, which reduced the hospital stay of these patients.
While the requirement of antiemetic dropped from 7 - 14
days before AHCC group to 3 - 5 days in AHCC group,
only 2 patients required hospitalization because of loose
motion in AHCC group compared to 6 patients without
AHCC group (Figure 2 and Table 3). Patiaents were
evaluated both clinically as well as radiologically to de-
termine tumor response. CT scan/MRI of the primary
tumor as well as neck nodes were performed after two
weeks of completion of at least six cycles of chemother-
apy. Tumor regressed in 11 patients, 8 patients had stable
disease and in rest of the patients, disease progressed
(Table 4).
4. Discussion
AHCC is an alpha-glucan rich nutritional supplement
extracted from the mycelia of shiitake (Lentinula edodes)
of the basidiomycetes family of mushrooms. These in-
tercellular chemical messengers trigger white blood cell
production and activity [3,4]. The therapeutic effect is
0
2
4
6
8
10
12
14
16
18
Blood
Transfusion
Growth
factor
Platelet
concentrate
pre-AHCC
post-AHCC
No. of patients
Figure 1. Comparison of hematological parameters in pa-
tients with and without AHCC, bringing down the blood
transfusion rate (16 vs 3). Total leukocyte and platelet count
also showed a slight fall in the patients with AHCC requir-
ing no platelet concentrate transfusion and only 7 patients
required growth factor supplement with AHCC.
0
5
10
15
20
25
Appetizer Loose motion Feeling better
without
AHCC
with AHCC
No. of patients
Figure 2. Comparison of quality of life concepts in patients
requiring appetizer, having loose motion and better general
condition with and without AHCC. While no patients with
AHCC required any appetizer and only 2 patients were hos-
pitalized for loose motion.
Table 3. Quality of life concept.
Without AHCC With AHCC
Confinement to bed 14 - 16 hr/day 8 - 10 h/d
Talking to people not yes
Sleep pattern irregular regular
Required antiemetic for
Chemo related
Nausea/vomiting
7 - 14 Days 3 - 5 Days
Table 4. Tumor response of the patients.
No. of patients
Complete Response 00
Partial Response 11
Stable Disease 08
Progressive Disease 06
Cop
yright © 2011 SciRes. IJCM
Integrating Complimentary and Alternative Medicine in Form of Active Hexose
591
Correlated Com
pound (AHCC) in the Management of Head & Neck Cancer Patients
predominantly seen in higher basidiomycete family [5].
St
udies show that AHCC also enhances production of
cytokines, including interferon γ, tumor necrosis factor-α
and interleukins (IL-2,4,6,10) [4]. In this present study
majority of the patients, who received AHCC along with
chemotherapy showed less fall in their hemoglobin level
and total leukocyte count. However, researchers have
found the influence of AHCC upon the innate immune
system in animal studies and published the results in
1992. AHCC significantly increased natural killer (NK)
cell activity in cancer patients, and also enhanced the
effects of killer T-cells, and cytokines (interferon, IL-12,
TNF-alpha) [3]. AHCC stimulates cell-mediated immu-
nity by activating the white blood cells, particularly
natural killer cells and macrophages, which directly at-
tack abnormal cells, virus-infected cells or external vital
and bacterial pathogens that enter the body. The funda-
mental mechanism of activating immunity is by means of
stimulating the number of dendritic cells as these cells
control the activities of B & T lymphocytic cells who are
the ultimate mediators of immunity and hence, affected
by AHCC. It also exhibits immunomodulating effects
partially by regulating thymic apoptosis [6]. Nomura T et
al. has published that besides immunogenic, AHCC is
also having anti-teratogenic effects in animal models [7].
Effective immunity has got direct impact on tumor con-
trol and better tolerability of chemotherapeutic agents. In
our series, it was significant that almost all the patients
who received AHCC, tolerated chemotherapy better
compared to their previous cycles of chemotherapy they
had received without AHCC. At least eighteen out of the
twenty-five patients acted as control of their own.
One major retrospective study suggests that AHCC
intake has a preventive effect in postoperative hepato-
cellular carcinoma patients [8,9]. The study has com-
pared the outcomes of 113 post-operative liver cancer
patients taking AHCC with 156 patients in the control
group. The results showed the rate of recurrence of ma-
lignant tumors was significantly lower (34.5% versus
66.1%) and patient survival was significantly higher in
the AHCC group (79.6% vs. 53.2%). We tried AHCC for
the first time in the patients suffering from cancers of
head & neck region and obtained good results.
AHCC has been studied extensively for safety in hu-
man trials as well as safety with conventional chemo-
therapy [10,11]. There are also few studies regarding the
interaction of AHCC with various kinds of chemothera-
peutic agents [12-15]. There is a great deal of scientific
evidence that AHCC not only helps to prevent the side
effects of chemotherapy, but enhances its primary effec-
tiveness as well. Several animal studies have shown that
AHCC was able to relieve the side effects of several
standard chemotherapy drugs like 5-FU, cisplatin, cyclo-
phosphamide, mercaptopurine, methotraxate etc. “Se-
vere” (50% to 100%) hair loss or alopecia caused by cy-
tosine arabinoside (Ara-C) was reduced to slight, when
AHCC was taken simultaneously. The ability of AHCC
to enhance the effectiveness of chemotherapy was dem-
onstrated in a study where rats were implanted with a cell
line of spontaneous mammary adenocarcinoma. In the
present study, the patients were administered AHCC along
with chemotherapeutic agents like paclitaxel, docetaxel,
cisplatin, 5-FU and certain monoclonal antibodies like
cetuximab and nimotuzumab (Table 2). All the patients
tolerated AHCC well. Routine side effects like nausea,
vomiting, loose motions were less in these patients.
5. Conclusions
It can be concluded that AHCC is safe to administer and
definitely helps cancer patients in reducing side effects of
chemotherapeutic drugs, getting a sense of wellbeing and
improved intake maintains general condition as well as
prepare them to continue and tolerate further cycles in a
better way. In advance stage disease achieving partial
response/stable disease is also of significance, particu-
larly when all the patients were having either recurrent or
residual disease. Whether AHCC is responsible for the
regression of the tumors, further trials are required to see
the effects of AHCC on tumor control. Also dose en-
hancement trial has to be undertaken.
6. Acknowledgements
This work was carried out as a collaborative project be-
tween the North Eastern Indian Gandhi Regional Institute
of Health and Medical Sciences and National Institute of
Biomedical Innovation. This project was supported by
the grant from the MEXT and MHLW, Japan and Amino
up chemical Co. Ltd, Sapporo, Japan. We thank Haruko
Ryo, National Institute of Biomedical Innovation for her
critical observations and proof reading.
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... 24) On the other hand, AHCC ® has no such side effects at normal intake levels and is distributed as a functional food. 14) An application of AHCC ® has been reported that AHCC ® is useful for the recuperation of cancer patients or their prognosis, 25) namely reducing the side effects of chemotherapeutic agents during cancer treatment, [26][27][28][29] preventing cancer recurrence, 30) improving the QOL prognosis, and reducing oxidative stress. 31) In this study, we found significant inhibitory effect of AHCC ® on the growth of renal cancer PDX and tendency of the inhibitory effect on the growth of breast cancer (invasive and non-invasive ductal carcinoma) PDX in Super SCID mice. ...
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... Comparison of toxicity (pre-vs posttreatment) in active hexose correlated compound (AHCC) and control groups. shown useful results in the treatment of various diseases including cancer and hepatitis as a complementary and alternative medicine in substantial medical institutions (18). Other studies have demonstrated that AHCC was effective in the treatment of infectious and inflammatory diseases as well as cancer (19)(20)(21). ...
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This review highlights some of the recently isolated and identified substances of higher Basidiomycetes mushrooms origin that express promising antitumor, immune modulating, cardiovascular and hypercholesterolemia, antiviral, antibacterial, and antiparasitic effects. Medicinal mushrooms have a long history of use in folk medicine. In particular, mushrooms useful against cancers of the stomach, esophagus, lungs, etc. are known in China, Russia, Japan, Korea, as well as the U.S.A. and Canada. There are about 200 species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. Searching for new antitumor and other medicinal substances from mushrooms and to study the medicinal value of these mushrooms have become a matter of great significance. However, most of the mushroom origin antitumor substances have not been clearly defined. Several antitumor polysaccharides such as hetero-beta-glucans and their protein complexes (e.g., xyloglucans and acidic beta-glucan-containing uronic acid), as well as dietary fibers, lectins, and terpenoids have been isolated from medicinal mushrooms. In Japan, Russia, China, and the U.S.A. several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms (Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used to treat a variety of disease states.
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Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4(+) and CD8(+) T cells, increased the number of tumor Ag-specific CD8(+) T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-gamma producing CD8(+) T cells. Interestingly, AHCC treatment also showed increased cell number of NK and gammadelta T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.