Clinically-Relevant Chemotherapy Interactions with Complementary and Alternative Medicines in ...

44 Pages·2009·0.51 MB·English

12 Recent Patents on Food, Nutrition & Agriculture, 2010, 2, 12-55
Clinically-Relevant Chemotherapy Interactions with Complementary and
Alternative Medicines in Patients with Cancer
Kevin Yi-Lwern Yap1,*, Cheng Shang See1 and Alexandre Chan1,2,*
1Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4,
Singapore 117543, 2Department of Pharmacy, National Cancer Centre Singapore, 11 Hospital Drive, Singapore
169610
Received: October 10, 2009; Accepted: October 30, 2009; Revised: November 14, 2009
Abstract: Complementary and alternative medicines (CAMs), in particular herbal medicines, are commonly used by
cancer patients in conjunction with chemotherapy treatment for their anticancer properties and supportive care. However,
the effects of many of these herbs are not well-documented due to limited studies done on them. Severe herb-drug
interactions (HDIs) have been recorded in some cases, and failure to recognize these harmful HDIs can lead to dire
consequences in cancer patients. This study discusses clinically-relevant interactions between anticancer drugs (ACDs)
and herbs classified into 7 categories: cancer treatment and prevention, immune-system-related, alopecia, nausea and
vomiting, peripheral neuropathy and pain, inflammation, and fatigue. Some promising patents which contain these herbs
and thus may manifest these interactions are also presented in this article. Pharmacokinetic interactions involved mainly
induction or inhibition of the cytochrome P450 isozymes and p-glycoprotein, while pharmacodynamic interactions were
related to increased risks of central nervous system-related effects, hepatotoxicity and bleeding, among others. Clinicians
should be vigilant when treating cancer patients who take CAMs with concurrent chemotherapy since they face a high risk
of HDIs. These HDIs can be minimized or avoided by selecting herb-drug pairs which are less likely to interact.
Furthermore, close monitoring of pharmacological effects and plasma drug levels should be carried out to avoid toxicity
and ensure adequate chemotherapeutic coverage in patients with cancer.
Keywords: Anticancer drugs, chemotherapy, complementary and alternative medicines, herb-drug interactions, traditional
chinese medicine.
INTRODUCTION and a similar trend is seen in the cancer population. A study
conducted on women with breast cancer showed an increase
Cancer is a highly prevalent health problem with increa-
in CAM usage from 66.7% in 1998 to 81.9% in 2005 [3]. A
sing incidence worldwide. It is a leading cause of death in
particularly large proportion of Asian patients also use
the United States (US), and is only superseded by heart
CAMs concurrently with their cancer therapies, ranging from
disease [1]. In 2007, one in eight deaths was due to cancer
45% of Japanese [5], 61% of Taiwanese [6], 76% and 67%
[2], while in 2008, the number of new cancer cases was
of Singaporean adults [7] and pediatric cancer patients [8]
expected to be about 1,437,180 with more than 565,000
respectively.
deaths [1]. It is estimated that the global burden of cancer is
expected to grow to 27 million new cancer cases and 17.5 Patients with cancer use CAMs for a variety of reasons.
million cancer deaths by 2050 [2]. This is a cause for con- These include having a more holistic approach for the
cern considering that cancers caused by cigarette smoking treatment of their cancer, as well as relieving the associated
and alcohol use can be prevented, while others such as breast side effects of chemotherapy (e.g. immunosuppression, can-
cancers can be avoided by regular screening examinations. cer pain, nausea and emesis) [9, 10]. In addition, some
patients also use CAMs for their anticancer properties as
Patients with cancer can be managed through surgery,
replacements for, rather than adjuncts to, mainstream
radiotherapy, immunotherapy, chemotherapy, or a combi-
therapy; some of which have limited evidence [11-13]. These
nation of these [1]. However, the use of complementary and
CAMs are usually taken without the physician’s knowledge,
alternative medicines (CAMs), including traditional Chinese
and patients tend to be resistant to discussions of their CAM
medicines (TCMs), has been gaining popularity in an
use with their physicians possibly due to clinician indif-
increasing number of patients with cancer in their course of
ference or opposition to CAM use, their clinician’s emphasis
therapy [3, 4]. CAM usage in the general US population has
on scientific evidence, or their anticipation of a negative
increased over the past 20 years, reaching 36% in 2002 [4],
response from the clinician [14]. Furthermore, the effects of

many CAMs are not well-documented due to the lack of
*Address correspondence to these authors at the Department of Pharmacy,
well-designed safety and efficacy studies [15]. As a result,
Faculty of Science, National University of Singapore, Block S4, 18 Science
drug-related problems such as herb-drug interactions (HDIs)
Drive 4, Singapore 117543, Tel: [phone], Fax: [phone],
E-mail: [email protected] between the anticancer drugs (ACDs) and CAMs may occur,
Department of Pharmacy, Faculty of Science, National University of which can lead to a compromise in the safety and efficacy of
Singapore, Block S4, 18 Science Drive 4, Singapore 117543; the chemotherapy treatment.
Tel: [phone]; Fax: [phone];
E-mail: [email protected]

1876-1429/10 $100.00+.00 © 2010 Bentham Science Publishers Ltd.
Chemotherapy Drug Interactions with Anticancer Herbs Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 13
ACD-CAM interactions may potentially be harmful to Manual [23], Lexi-Comp’s Drug Information Handbook
patients due to the narrow therapeutic indices of ACDs. (15th ed.) [24], Lexi-Comp’s Drug Information Handbook for
HDIs can lead to either an increased toxicity or sub-thera- Oncology (6th ed.) [25], PharmGKB [26], Pharmacology and
peutic effects. The potential for an interaction is ~6% when Applications of Chinese Materia Medica [27], Aetna
two drugs are prescribed concurrently, and the probability Intelihealth® [28], TCM Assistant [29], Memorial Sloan-
increases as more drugs are used concurrently [16]. Little Kettering [30], Micromedex® v.5.1. [31], Natural Medicines
information exists for CAMs. However, a similar deduction Comprehensive Database (10th ed.) [32], Drugs.com [33],
can be drawn from this trend regarding the likelihood of Caremark Drug Interactions [34] and DoubleCheckMD [35].
ACD-CAM interactions. In addition, some CAM products The first 11 sources were used to gather information on the
may contain multiple pharmacologically active constituents, pharmacokinetics of ACDs, characteristics and clinical
which may further increase the risk of ACD-CAM inter- indications of CAMs, while the latter 6 were used to compile
actions. These interactions can lead to significant clinical interaction data with ACDs. Interaction checkers were used
consequences and possibly even fatal outcomes [17]. HDIs for the gathering of HDI information where applicable.
can play an important role in clinical decision making in 3 When there was no interaction information available through
situations: (a) adding an interacting herb to existing chemo- the checkers, the monographs of the ACDs and CAMs would
therapy; (b) adding a chemotherapeutic treatment regime to be consulted instead. In addition, published literature from
the interacting herb; and (c) removing an interacting herb PubMed was also used to supplement our review based on
from long-term chemotherapy. the following keywords: “anticancer drugs”, “chemo-
therapy”, “complementary and alternative medicines”, and
Drug interactions can be pharmacokinetic or pharmaco-
“herb-drug/ drug-herb interactions”. Alternative therapies
dynamic in nature. Although drug interactions typically refer
(e.g. Ayurveda), substances with limited documentation on
to drug-drug interactions, other interactions such as food-
their medicinal properties (e.g. alkaline water), vitamins and
drug or herb-drug interactions also exist, and are important
minerals, and commercial supplements were excluded from
considerations in the therapeutic care of a patient. Phar-
our search.
macokinetic interactions usually involve changes in absorp-
tion, distribution, metabolism or elimination of a drug, which A list of patents containing CAM products was also
can be due to either enzyme induction or inhibition [18]. On collated from the patent databases by the United States
the other hand, pharmacodynamic interactions can result in Patent and Trademark Office [36, 37], European Patent
antagonistic, additive or synergistic effects [18]. Albeit the Office [38], Free Patents Online [39] and Google Patents
fact that pharmacodynamic interactions form the basis of the [40], with the keywords “anticancer herbs” and “comple-
multiple-agent chemotherapy cocktails used in improving the mentary and alternative medicines”. Only patents in which
clinical response in patients with cancer, other undesirable the CAM constituents were documented were included in
clinical consequences can also occur in these patients [18, our search. Patents were limited to only those that were
19]. For example, the concomitant use of trastuzumab and approved from the year 2000, and had to include at least one
anthracyclines can result in an increased risk of cardiac of our compiled CAMs based on our search strategy
toxicities [20], while the combined use of rituximab and previously described. Patent applications that were submitted
cisplatin can also predispose patients to severe renal toxicity, but not approved with a patent number were excluded from
including acute renal failure [21]. our search.
Clinicians must be vigilant when treating patients with
RESULTS
cancer who are concurrently on both chemotherapy and
CAMs so as to avoid unwanted toxicities and inadequate
drug exposures due to the HDIs. Hence, this review aims to Classification of Herb-Drug Interactions Between
highlight the common types of interactions that are observed Anticancer Drugs and Complementary and Alternative
Medicines
between ACDs and CAM herbs which are indicated for
cancer treatment, prevention, and supportive care. With the This paper identifies the clinically important HDIs
advent of new CAM products and supplements in the consu- between ACDs used in chemotherapy and CAMs which have
mer market, this paper will also illustrate some HDIs that are
indications in cancer treatment, prevention and supportive
clinically-relevant in patients with cancer through a discus-
care. The CAMs are categorized into 7 classes based on their
sion of how these HDIs are related to CAM products that
indications in cancer therapy: (a) cancer treatment or pre-
have recently been patented. Although this review is not vention, (b) immune-system-related, (c) alopecia, (d) nausea
exhaustive, it is intended to increase the clinicians’ aware- and vomiting, (e) peripheral neuropathy and pain, (f)
ness of potential HDIs, so that appropriate adjustments can inflammation, and (g) fatigue syndrome. As such, the rest of
be made to optimize the outcomes of chemotherapy. A
this paper discusses the HDIs in greater detail based on these
holistic view comprising the risks and benefits of ACD-
7 categories of CAMs. Patents which fall within these
CAM combinations should be considered by clinicians in the
categories will also be listed in their respective sections.
treatment of patients with cancer. Tables 1 to 3 provide a summary of all the ACDs, CAMs
and patents that were identified in our review. In addition,
SEARCH STRATEGY
the HDIs that were identified based on our findings are
A list of ACDs and CAMs was compiled from a total of detailed in Table 4 [41-168], sorted according to alphabetical
14 sources, which consisted of reference books and online order of the CAMs. The active constituents of certain CAMs
databases. These included the British National Formulary that are deemed responsible for these HDIs are also provided
(53rd ed.) [22], BC Cancer Agency (BCCA) Cancer Drug in Fig. (1) [169-176], where applicable.
14 Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 Yap et al.
Table 1. List of Anticancer Drugs (ACDs) Identified in our Review, Classified Based on their Pharmacological Classes
List of ACDs
Alkylating agents
Altretamine, busulfan, carmustine, chlorambucil, cyclophosphamide, dacarbazine, estramustine, ifosfamide, lomustine, mechlorethamine, melphalan
procarbazine, thiotepa, temozolomide, treosulfan
Antimetabolites
Azacitidine, capecitabine, cladribine, clofarabine, cytarabine, fludarabine, fluorouracil, gemcitabine, mercaptopurine, methotrexate, pemetrexed, pentostatin
raltitrexed, tegafur, thioguanine
Antimicrotubules
Docetaxel, ixabepilone, paclitaxel, vinblastine, vincristine, vindesine, vinorelbine
Biological modifiers
Aldesleukin, denileukin, filgrastim, interferon alfa-2a and -2b, pegfilgrastim, sargramostim
Corticosteroids
Dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone
Hormone agonists/antagonists
Anastrozole, bicalutamide, buserelin, cyproterone, exemestane, flutamide, fulvestrant, goserelin, lanreotide, letrozole, leuprolide, medroxyprogesterone
megestrol, nilutamide, norethisterone, octreotide, tamoxifen, toremifene, triptorelin
Platinum compounds
Cisplatin, carboplatin, oxaliplatin
Topoisomerase inhibitors
Amsacrine, daunorubicin, doxorubicin, epirubicin, etoposide, idarubicin, irinotecan, mitoxantrone, topotecan
Tyrosine kinase inhibitors and monoclonal antibodies
Alemtuzumab, bevacizumab, bortezomib, cetuximab, dasatinib, erlotinib, gefitinib, gemtuzumab, ibritumomab, imatinib, lapatinib, rituximab, sorafenib
sunitinib, tositumomab, trastuzumab
Other ACDs
Angiogenesis inhibitor: Thalidomide
Antidotes: Leucovorin, mesna
Cardioprotectant: Dexrazoxane
Cytotoxic antibiotics: Bleomycin, dactinomycin, mitomycin
Histone deacetylase inhibitor: Vorinostat
Mammalian target of rapamycin (mTOR) inhibitor: Temsirolimus
Photosensitizing agent: Temoporfin
Retinoid: Alitretinoin, bexarotene, tretinoin
Miscellaneous: Arsenic trioxide, asparaginase, hydroxyurea, mitotane, palifermin, pegaspargase, porfimer, trabectedin
HERB-DRUG INTERACTIONS BASED ON CANCER breast cancer cells [174], and epidemiological studies have
INDICATIONS also indicated that it can improve survival and quality of life
in breast cancer patients [175]. On the other hand, Asian
Cancer Treatment and Prevention
ginseng (Panax ginseng) has also been researched for its use
A large proportion of CAMs identified in this article are in a wide variety of cancers and its effects on the immune
indicated for cancer treatment and prevention Table 2. system [84, 176, 177]. These ginsengs may precipitate an
Among these, a number have been identified to have inter- interaction with ACDs that have monoamine oxidase (MAO)
actions with ACDs. One common herb used for its inhibitory activity, such as procarbazine. Several case reports
adaptogenic effects is ginseng. The major active components of patients suffering from insomnia, headaches, tremors and
in ginsengs are the triterpene glycosides called ginsenosides, hypomania during concomitant administration of ginseng
of which more than 30 different ginsenosides are known and phenelzine have been published [17, 85-88]. This is a
[169]. The antiproliferative effects of American ginseng result of the potentiation of the MAO inhibition effects of
(Panax quinquefolius) has been demonstrated in human phenelzine. Thus, this combination should be avoided in
cancer patients undergoing procarbazine therapy.
Chemotherapy Drug Interactions with Anticancer Herbs Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 15
Table 2. List of Complementary and Alternative Medicines (CAMs) Identified in our Review, Classified Based on their Cancer
Indications*
List of CAMs
Cancer treatment and prevention
714X (trimethylaminohydroxybicycloheptane chloride), agrimony grass (Agrimonia pilosa), alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid), amygdalin
(D-mandelonitrile-b-D-glucosido-6-b-D-glucoside), anvirzel/ oleandrin (Nerium oleander), Arisaema rhizome (Arisaema sp.), astragalus (Astragalus
membranaceus), barley (Hordeum vulgare), bee pollen, bilberry fruit (Vaccinium myrtillus), bitter melon (Momordica charantia), black nightshade
(Solanum nigrum), bloodroot (Sanguinaria canadensis), blue-green algae (Spirulina platensis), bupleurum (Bupleurum sp.), burdock (Arctium majus),
calcium glucarate (D-glucaro-1,4-lactone), cascara (Rhamnus purshiana), cassia bark (Cinnamomum sp.), cat's claw (Uncaria tomentosa), Cephalotaxaceae
(Cephalotaxus fortunei), chaparral (Larrea sp.), Chinese anemone root pulsatilla (Pulsatilla chinensis), Chinese asparagus (Asparagus cochinchinensis),
cordyceps (Cordyceps sinensis), Coriolus versicolor (Coriolus versicolor), dong quai (Angelica sinensis), evening primrose oil (Oenothera biennis), evodia
(Evodia sp.), fenugreek (Trigonella foenum-graecum), forskolin (Coleus forskohlii), fourstamen stephania root (Stephania tetrandra), garlic (Allium
sativum), American ginseng (Panax quinquefolius), Siberian ginseng (Eleutherococcus senticosus), glossy privet fruit (Ligustrum lucidum Ait), goldenseal
(Hydrastis canadensis), gotu kola (Centella asiatica), green tea (Camellia sinensis), indigo (Isatis tinctoria), isatis leaf and root (Isatidis baphicacanthi,
Isatis sp.), licorice (Glycyrrhiza sp.), maitake (Grifola frondosa), milk thistle (Silybum marianum, Carduus marianum), European mistletoe (Viscum sp.),
mume fruit (Prunus mume), noni (Morinda citrifolia), pau d'arco (Tabebuia sp.), pennyroyal (Mentha pulegium, Hedeoma pulegioides), Pinellia rhizome
(Pinella sp.), pokeweed (Phytolacca americana), Rabdosia rubescens (Rabdosia rubescens), Rhizoma iphigenia indica (Iphigenia indica), rhubarb (Rheum
sp.), saw palmetto (Serenoa repens), skullcap (Scutellaria sp.), sheep sorrel (Rumex acetosella), shiitake mushroom (Lentinula edodes), slippery elm (Ulmus
rubra), sophora root (Sophora subprostata), soy (Glycine max), spreading hedyotis (Hedyotis sp.), stillingia (Stillingia sylvatica), Trichosanthes root
(Trichosanthes sp.), turmeric (Curcuma sp.)
Immune-system-related
Astragalus (Astragalus membranaceus), bee pollen, bitter melon (Momordica charantia), blue-green algae (Spirulina platensis), cat’s claw (Uncaria
tomentosa), cordyceps (Cordyceps sinensis), Coriolus versicolor (Coriolus versicolor), Echinacea (Echinacea purpurea), American ginseng (Panax
quinquefolius), Asian ginseng (Panax ginseng), Siberian ginseng (Eleutherococcus senticosus), glossy privet fruit (Ligustrum lucidum Ait), goldenseal
(Hydrastis canadensis), maitake (Grifola frondosa), European mistletoe (Viscum sp.), mume fruit (Prunus mume), noni (Morinda citrifolia), reishi
mushroom (Ganoderma lucidum), rhubarb (Rheum sp.), shiitake mushroom (Lentinula edodes)
Alopecia
Fenugreek (Trigonella foenum-graecum), psoralea fruit (Psoralea corylifolia), Swertiae herba (Swertia sp.)
Nausea and vomiting
Ginger (Zingiber officinale), peppermint (Mentha sp.)
Peripheral neuropathy and pain
Achyranthes root (Achyranthes sp.), aloe vera (Aloe sp.), capsaicin (Capsicum sp.), corydalis (Corydalis turtschaninovii), devil's claw (Harpagophytum
procumbens), divaricate saposhnikovia root (Ledebouriella sp., Siler divaricatum, Saposhnikovia divaricata, Stenocoelium divaricatum), eucommia bark
(Eucommia ulmoides), fourstamen stephania root (Stephania tetrandra), Asian ginseng (Panax ginseng), maté (Ilex paraguariensis), noni (Morinda
citrifolia), Rhizoma sinomenii acuti (Sinomenium acutum), Schefflera (Schefflera sp.), St. John's wort (Hypericum perforatum), willow bark (Salix alba)
Inflammation
Achyranthes root (Achyranthes sp.), aloe vera (Aloe sp.), arnica (Arnica montana), berberidaceae (Berberis sp.), black nightshade (Solanum nigrum),
bupleurum (Bupleurum sp.), butcher's broom (Ruscus aculeatus), cat's claw (Uncaria tomentosa), German chamomile (Matricaria recutita L.), chaparral
(Larrea sp.), cinnamon (Cinnamomum sp.), comfrey (Symphytum officinale), devil's claw (Harpagophytum procumbens), divaricate saposhnikovia root
(Ledebouriella sp., Siler divaricatum, Saposhnikovia divaricata, Stenocoelium divaricatum), eucommia bark (Eucommia ulmoides), fenugreek (Trigonella
foenum-graecum), forsythia fruit (Forsythia sp.), fourstamen stephania root (Stephania tetrandra), gotu kola (Centella asiatica), licorice (Glycyrrhiza sp.),
lobelia (Lobelia inflata), nettle (Urtica dioica), pennyroyal (Mentha pulegium, Hedeoma pulegioides), pseudoginseng (Panax notoginseng), pygeum
(Pygeum africanum), rehmannia root (Rehmannia glutinosa), reishi mushroom (Ganoderma lucidum), Rhizoma sinomenii acuti (Sinomenium acutum),
rhubarb (Rheum sp.), sassafras (Sassafras albidum), saw palmetto (Serenoa repens), skullcap (Scutellaria sp.), sheep sorrel (Rumex acetosella), slippery elm
(Ulmus rubra), Solomon’s seal (Polygonatum sp.), tea tree oil (Melaleuca alternifolia), tree peony bark (Paeonia suffruiticosa), turmeric (Curcuma sp.)
willow bark (Salix alba)
Fatigue syndrome
Blue-green algae (Spirulina platensis), cordyceps (Cordyceps sinensis), guarana (Paullinia cupana), maté (Ilex paraguariensis), St. John's wort (Hypericum
perforatum)
Other conditions experienced by patients with cancer
Black cohosh (Cimicifuga racemosa), dong quai (Angelica sinensis), ginkgo (Ginkgo biloba), valerian (Valeriana officinalis)
*CAMs that have multiple uses are listed in their respective categories
16 Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 Yap et al.
Table 3. List of Approved Patents with their Indications in Cancer Therapy
Authors Patent Number, Title Description of Active Constituents Mechanism of Indication in
Date of Patent Anticancer Action Cancer Therapy
Publication
Arntzen, C.J., US20067105186, Triterpene A method and Contains triterpene Induces apoptosis Cancer treatment
Blake, M.E., September 12, 2006 compositions composition of glycosides isolated from and cytoxicity in and prevention
Gutterman, J.U. and methods saponin mixtures the root tissues of Acacia Jurkat cells, and
for use thereof isolated from the victoriae (Benth.) inhibits the
Arntzen, C.J., US20046746696,
species Acacia (family: Leguminosae) initiation and
Gutterman, J.U. June 8, 2004
victoriae, which promotion of
exhibits potent anti- mammalian
tumor effects epithelial cells to a
premalignant or
malignant state
Aylward, J.H. US20026432452, Anti-cancer A method and Contains extracts from Selective Cancer treatment
August 13, 2002 compounds composition that is Euphorbia peplus, cytotoxicity has and prevention

useful in the Euphorbia hirta and been shown against
treatment of cancers, Euphorbia drummondii several different
US20087410656, particularly (family: Euphorbiaceae). tumor cell lines
August 12, 2008 malignant

melanomas and
squamous cell
carcinomas.
Chan, P.-K., US20097524824, Composition A composition of Contains saponin extracts Inhibitory activity Cancer treatment
Mak, M.S., April 28, 2009 comprising extracts used to treat from the husk or fruit towards tumor and prevention
Wang, Y. Xanthoceras a variety of cancers stem of Wenguanguo growth in various

sorbifolia such as those of (Xanthoceras sorbifolia human cancer cell

extracts, breast, leukocyte, Bunge), also known as lines
compounds liver, ovarian, goldenhorn and
isolated from bladder, prostate, yellowhorn
same, methods bone or brain
for preparing
same and uses
thereof
Chan, P.-K., US20097514412, Anticancer Uses, functions and Contains extracts from Inhibitory activity Cancer treatment
Mak, M.S., April 7, 2009 biangeloyl methods of Wenguanguo towards tumor and prevention
Wang, Y. saponins preparation related to (Xanthoceras sorbifolia growth in various
US20077262285,
the extracts from Bunge), also known as human cancer cell

August 28, 2007
Wenguanguo goldenhorn and lines
(Xanthoceras yellowhorn, and plants

sorbifolia) from the Sapindaceae
family
Cheng, Y.-C., US20097534455, Herbal A herbal Contains Scutellaria Increases the Cancer treatment
Liu, S.-H. May 19, 2009 composition composition used in baicalensis Georgi therapeutic indices and prevention
PHY906 and the treatment of (scute), Glycyrrhiza of chemotherapy

its use in diseases, particularly uralensis Fisch (licorice), drugs
US20067025993, chemotherapy viral infections and Fructus ziziphus jujuba
April 11, 2006 neoplasms (date), and Paeonia
lactiflora pall (white
peony root), together with
one or more
chemotherapy agents
Chemotherapy Drug Interactions with Anticancer Herbs Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 17
(Table 3) Contd….

Authors Patent Number, Title Description of Active Constituents Mechanism of Indication in
Date of Patent Anticancer Action Cancer Therapy
Publication
Chou, W.H. US20087465466 Compositions A method and Contains Herba epimedii Works directly on Cancer treatment
December 16 and methods for composition used in and at least 3 prostate cancer and prevention

2008 prostate and patients with prostate supplemental herbs from cells to stop cell
kidney health or kidney disorders, a group consisting of proliferation and
and disorders, including prostate Fructus rosae laevigatae induce apoptosis.
US20087449202 an herbal cancers Fructus rubi, Fructus Fructus psoraleae
November 11 preparation psoralea, Radix morindae Semen cuscutae

2008 officinalis, Fructus and Fructus

schisandrac chinensis ligustri lucidi have
Fructus ligustri lucidi been suggested to
US20077223424
Semen cuscutae, and demonstrate
May 29, 2007
Radix astragali. Also anticancer activity
contains icariin, ursolic

acid, ellagic acid
US20056855344
psoralen,
February 15,
deoxyschizandrin
2005
oleanolic acid, quercetin
aslvagaloside, and an
extract of Radix morindae
officinalis
Djang, A.H.K. US20016168795 Method for A method of therapy Contains extracts of Inhibits tumor Cancer treatment
January 02, 2001 anticancer which involves Gynostemma growth in human and prevention
therapy using administering a pentaphyllum, Camellia tumor xenografts
an herbal herbal extract for sinensis (green tea), and
extract treating cancer in Crataegus pinnatifida
composition individuals (hawthorn berries)

Einbond, L.S. US20087407675 Anti-neoplastic A composition for Contains an ethyl acetate Induces cell-cycle Cancer treatment
August 5, 2008 compositions treating or extract of black cohosh, arrest and inhibits and prevention
Weinstein, I.B.
comprising preventing neoplasia and other tumor growth in

extracts of chemopreventive or vitro

black cohosh chemotherapeutic agents
Han, P., Guo, US20026451353 Fagopyrum A method and Contains tannin and Clinical studies Cancer treatment
O., Chen, B., September 17 cymosum composition of epicatechin extracts of carried out by the and prevention
Zhu, H. 2002 (Trev.) Meisn Fagopyrum cymosum Fagopyrum cymosum authors suggest

composition (Trev.) Meisn, used (Trev.) Meisn, also therapeutic
method to in the treatment of known as buckwheat efficacy in the
US20046726938 prepare and cancers and (family: Polygonaceae) treatment of lung
April 27, 2004 analyze the alleviating the toxic cancers when used

same and uses and adverse effects alone or in
thereof of chemotherapy and combination with
radiotherapy chemotherapy and
radiotherapy, as
well as reduction
of toxic and
adverse effects of
chemotherapy and
radiotherapy
18 Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 Yap et al.
(Table 3) Contd….

Authors Patent Number, Title Description of Active Constituents Mechanism of Indication
Date of Patent Anticancer Action in Cancer
Publication Therapy
Haridas, V., US20056962720 Triterpene A composition of Contains triterpene Induces apoptosis and Cancer
Gutterman, November 8, 2005 compositions saponin mixtures glycosides isolated from the cytoxicity in Jurkat cells, treatment
J.U. and methods for isolated from root tissues of Acacia and inhibits the initiation and
use thereof Acacia victoriae victoriae (Benth.) (Family: and promotion of prevention
which exhibits Leguminosae) mammalian epithelial
potent anti-tumor cells to a premalignant

effects or malignant state

Ho, C.-T., US20087351739 Bioactive A preparation of Contains Rabdosia rubescens Exhibits anti-angiogenic Cancer
Bai, N., April 1, 2008 compounds and compositions and (Hemsl.) Hara (donglingcao) effects in vitro treatment
Dong, Z., methods of uses kits comprising of formerly known as Isodon and

Bode, A.M., thereof compounds for the rubescens (Family: prevention
Dushenkov, prevention or Labiatae), whose active

S. treatment of constituents include
cancers rubescensin A (oridonin) and
rubescensin B (ponicidin)
Hsieh, C.F. US20097527812 Herbal A herbal Contains Wubeizi (gall Induces apoptosis in a Cancer
May 5, 2009 composition for composition that produced by Melaphis variety of cancer cells, treatment

treating cancer provides anticancer chinensis (Bell) Baker), particularly with breast and

effects, particularly Lonicera japonica, cancer cells prevention
for breast cancers Astragalus membranaceus,
Rehmanniae Radix (root of
Rehmannia glutinosa
Libosch), Glycyrrhizae
Radix, and Panax ginseng
Huang, US20077201928 Extracts of A method and Contains orange peel extract The orange peel extract Cancer
M.T., Ho, April 10, 2007 orange peel for composition used used alone or in combination inhibits tumor growth in treatment
C.-T., Rosen, prevention and in the treatment with rosemary and Mexican vivo and
R.T., Ghai, treatment of and prevention of bamboo extracts, a Huzhang prevention
G., Lipkin, cancer colon cancer extract, resveratrol, a black

M., Chen, tea extract and/or a

K.Y., hydroxylated or
Telang, N., methoxylated resveratrol
Boyd, C., analog
Csiszar, K.
Jo, S.K., US20056964785 Herbal A composition for Contains Angelicae gigantis Inhibitory effects against Cancer
Kim, S.H., November 15 composition for improving Radix, Cnidium officinale tumor cell growth; treatment
Yee, S.T., 2005 improving anticancer activity, Makino and Paeonia immunostimulation; and
Park, H.R., anticancer immune response japonica Miyabe et Takeda improves hematopoietic prevention,
Oh, H., activity, and hematopoiesis, function by stimulating immune-
Byun, M.W. immune as well as the proliferation of bone system-
response and protecting the body marrow cells and related

hematopoiesis from oxidative improving the recovery
of the body, and damage of the hematopoietic
protecting the system from oxidative
body from damage; inhibits
oxidative oxidative damage of
damage, and the intracellular DNA,
method of chromosomes, lipids and
preparing the proteins; and free-radical
same scavanging effects
Chemotherapy Drug Interactions with Anticancer Herbs Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 19
(Table 3) Contd….

Authors Patent Number, Title Description of Active Constituents Mechanism of Indication
Date of Patent Anticancer Action in Cancer
Publication Therapy
Khanuja, US20087375260, High artemisinin A method of Contains Artemisia annua Artemisinins are Cancer
S.P.S., Paul, May 20, 2008 yielding artemisia developing a novel, 'CIM-Arogya', also known as suggested to have treatment
S., Shasany, plant named distinct high herb qinghao plant (family: immunosuppressive and
A.K., Gupta, ‘CIM-arogya’ and artemisinin Asteraecae, active and potential prevention,
A.K., yielding genotype of component: artemisinin) anticancer activities immune-
Darokar, Artemisia annua at substantially system-

M.P., Gupta, obtained through higher doses than related
M.M., marker-assisted that for antimalarial

Verma, R.K., breeding activities
Ram, G.,
Kumar, A.,
Lal, R.K.,
Bansal, R.P.,
Singh, A.K.,
Bhakuni,
R.S.,
Tandon, S.
Kim, H., US20026420348, Pectic A purification Contains an extract of acidic Immunostimulatory Immune-
Kim, I., Han, July 16, 2002 polysaccharides method and pectic polysaccharide effects through the system-
S., Ahn, K., purified from composition of compounds from Angelica enhancement B-cell related

Hong, N. Angelica gigas aqueous extracts of gigas Nakai antibody production

nakai and Angelica gigas Nakai and augmentation of

purification roots used in the T-dependent
method and use as treatment or antibody response
immunostimulatin prophylaxis of
g agent thereof immune-related
diseases and in basic

immunology
research
Kuo, K.W. US20067078063, Water soluble A composition of Water-soluble extracts of Inhibition of growth Cancer
July 18, 2006 extract from plant water-soluble plants from Solanum incanum and initiation of treatment
of Solanum genus extracts from plants L., Solanum indicum apoptosis of cancer and

and the of the Solanum genus Solanum nigrum, Solanum cells in vivo prevention
preparation capsicastrum, Solanum

process thereof, xanthocarpum, Solanum
and melongena, Solanum
pharmaceutical coagulans, Solanum
composition tunigrum, Solanum
containing the sodomeum, Solanum
water soluble turburosum, Solanum
extract aculeastrum, Solanum
lycocarpum, Solanum
khasianum, Solanum
suaveolens, Solanum uporo
Solanum abutiloides,
Solanum coccineum, Solanum
unguiculatum, Solanum
robustum, Solanum anguivi
Solanum platanifolium
Solanum mammosum
consisting of at least 60-90%
of solamargine and
solasonine
20 Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 Yap et al.
(Table 3) Contd….

Authors Patent Number, Title Description of Active Constituents Mechanism of Indication
Date of Patent Anticancer Action in Cancer
Publication Therapy
Kuok, K.Y., US20046790464, Herbal A method and Contains Radix Asparagi Reduces tumor Cancer
Ly, H. September 14 compositions for composition used for Radix Angelicae progression in vivo. treatment
2004 prostate the prevention and pubescentis; Radix and
conditions treatment of prostate Trichosanthis; Radix prevention
gland disorders Scuttellariae; Radix
specifically prostate Angelicae sinensis; Radix
carcinoma, benign Dipsaci; Cortex
prostate hyperplasia Eucommiae; Medulla
and prostatitis Junci; Rhizoma
Anemarrhenae; Caulis
akebiae; Herba dianthi;
Semen plantaginis;
Cortex Phellodendri
(fried); Radix et rhizoma
rhei; Rhizoma seu Radix
Notopterygii; Olibanum
Fructus gardeniae; Radix
astragali seu hedysari
Rhizoma Cimicifugae
Radix Bupleuri; Myrrha
Gypsum fibrosun; Radix
Rehamanniae (crude)
Folium Pyrrosiae
Rhizoma acori graminei
Rhizoma Dioscoreae
hypoglaucae; Radix
Linderae; Herba
Cistanche; Radix
Paeoniae rubra; Rhizoma
Dioscoreae; Semen
euryales; Cortex Mouton
Polyporus umbellatus
Radix Rehmanniae
praeparata; Medulla
Tetrapanacis; Semen
coicis; Fructus Horedi
germinatus (Poria); Radix
Aconitip Praeparata
Rhizoma Alismatis Cortex
Cinnamomi; Herba Asari
Radix Glycyrrhizae
Stigma maydis; Phaseolus
radiatus L., and
optionally, Ganoderma
lucidum
Lee, C.-Y. US20067005146, Complex A complex Contains Pilose asiabell These herbs aim to Immune-
February 28, 2006 prescription of prescription of herbal root (dangshen) improve the following system-
Chinese medicines for the Astragalus root phenomena according to related
medicine for the treatment of (huanggi), Coix seed traditional Chinese
treatment of extensive cancers or (yiyiren), Eupatorium medicinal principles: (a)
extensive cancer cancers related to the (shanpeilan), Tangerine "enhance pancreas
lymph nodes peel (chenpi), Justicia function and maintain
Chemotherapy Drug Interactions with Anticancer Herbs Recent Patents on Food, Nutrition & Agriculture, 2010, Vol. 2, No. 1 21
(Table 3) Contd….

Authors Patent Number, Title Description of Active Constituents Mechanism of Indication
Date of Patent Anticancer Action in Cancer
Publication Therapy
(juechuang), Prunella Links with other organs"
spike (xiakucao), Serissa (b) "remove the
serissoides (liangfencao) obstruction in the portal
Capejasmine fruit (zhizi) vein, liver and spleen
Forsythia fruit (liangiao) maintain and decrease
Red peony root (chishao) the portal vein pressure"
Rhubarb (dahuang) (c) "improve the defense
Blister beetle (zhechong) functions and lymph
Oldenlandia (bai huashe- circulation, increase
shecao), Polygonum immunity", and (d) "pass
perfoliatum through lymphatic node
(gangbanggui) and other necessary
Subprostrate sophora root effects"
(shandougen) Shrubalthea

bark (mujinpi), Rhizome
of arisaema
(tiannanxing), Chinese
Lobelia (banbianlian)
Ampelopsis (bailian)
Globethistle (loulu),
Pyrrosia leaf (shiwei)
Frankincense (ruxiang)
Myrrh (moyao), Paris
chinensis franch (zao
xiu), Patrinia (baijiang)
Dahurian angelica root
(baizhi), Belamcanda
rhizome (shegan)
Dandelion herb
(pugongying)
Lemmaphyllum
microphyllum
(luoyancao), Gleditsia
spine (zaojia), Pubescent
angelica root (duhuo)
Chinese ephedra
(mahuang), and
Cimicifuga rhizome
(sheng ma). Fuling
(Indian bread, or Poria) is
also included as an
excipient
Lee, S.-H., US20056902748 Medicines A composition of Terpenoid saponins, Produces inhibitory Cancer
Lee, Y.-C., June 7, 2005 manufactured extracts from inclusive of platyconin A effects against the treatment
Jung, Y.-C., from old platycodon which C, D, D6, polygalasin D adhesion of cancer cells and

Seo, J.-K., platycodon has a variety of and D2, from Platycodon and an immuno- prevention,
Noh, J.-S. extracts physiological effects, grandiflorum A.DC enhancing effect immune-
including system-
immunostimulatory related
and anticancer
effects