Annals of Oncology original articles

Annals of Oncology 23: 211221, 2012

doi:10.1093/annonc/mdr054
Published online 29 March 2011

Integrative oncology in the Middle East: from traditional

herbal knowledge to contemporary cancer care
E. Ben-Arye1,2*, E. Schiff3,4, E. Hassan5, K. Mutafoglu6, S. Lev-Ari7, M. Steiner8, O. Lavie9,
A. Polliack10, M. Silbermann11 & E. Lev12
1
Integrative Oncology Program, The Oncology Service and Lin Medical Center, Clalit Health Services, Haifa, Israel; 2Complementary and Traditional Medicine Unit,
Department of Family Medicine, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 3Department of Internal Medicine, Bnai-Zion Hospital, Haifa,
Israel; 4Department for Complementary/Integrative Medicine, Law and Ethics,The International Center for Health, Law and Ethics, Haifa University, Haifa, Israel;
5
Department of Botany, National Research Centre, Dokki, Giza, Egypt; 6Department of Pediatric Oncology, Institute of Oncology, Dokuz Eylul University, Inciralti Izmir,
Turkey; 7Complementary Medicine Unit, Tel-Aviv Medical Center, Tel-Aviv; 8Department of Oncology, The Oncology Service and Lin Medical Center, Clalit Health
Services, Haifa; 9Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa; 10Department of Hematology, Hadassah University Hospital, Hebrew
University Medical School, Jerusalem; 11The Middle East Cancer Consortium, Haifa; 12Department of Eretz Israel Studies, University of Haifa, Haifa, Israel

Received 24 December 2010; revised 5 February 2011; accepted 7 February 2011

Background: Based on traditional, historical, ethnobotanical, laboratory, and clinical findings, we present research
framework aiming to identify Middle Eastern herbs that are worthy of further research for their anticancer potential.
Methods: A comprehensive research project was developed by a multinational team comprising family physicians,
medicine specialists, oncologists, an Islamic medicine history specialist, a traditional medicine ethnobotanist, and
a basic research scientist. The project followed two consecutive phases: (i) historical and ethnobotanical search for
cancer-related keywords and (ii) Medline search for in vitro and in vivo studies.
Results: This search yielded 44 herbs associated with cancer care. The Medline search yielded 34 herbs of which 9
herbs were reported in various clinical studies.
Conclusions: This multidisciplinary survey was found to be a valuable way to identify herbs with potential clinical
significance in cancer care. Based on this pilot study, it is suggested that the Middle East can serve as a valuable
region for future multicultural-oriented cancer research.
Key words: cancer, herbal medicine, Islamic medicine, oncology, traditional medicine

introduction further search for additional herbs can yield identification of

Ethnobotanical research is a valuable source for identifying herbs
with anticancer properties. Medicinal herbs such as Catharanthus
roseus and Pacific yew (Taxus brevifolia) were used for hundreds
of years as traditional remedies and were subsequently
discovered as a source for chemotherapy drugs (vincristine/
vinblastine and taxanes) [1, 2]. Other herb-originated drugs, such
as morphine (derived from opium poppyPapaver
somniferum [3]), and psychoactive substances derived from
Cannabis sativa have been in use to alleviate pain and
improve patient well-being. Thus, it is conceivable that
*Correspondence to: Dr E. Ben-Arye, Department of Oncology, The Oncology Service,
Lin Medical Center, 35 Rothschild Street, Haifa 35152, Israel. Tel: +972-4-856-8334;
Fax: +972-4-856-8249; E-mail: eranben@netvision.net.il
The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com
more herbs with anticancer activity such as ayurvedic medicine in
India [4] and shamans in the Amazon rain forest [5].
The use of herbs for treatment of various ailments has been
documented in the Middle East for generations [6], and plant
remnants were already found in prehistoric sites dating back
to 19 000 BC (Ohalo) [7] and 60 000 BP (Kebara Cave) [8].
During the Middle Ages, Islamic medicine was considered the
leading medical scheme involving traditional medical
practices in the Middle East, Africa, India, and the far East [9],
along with GreekRoman-based European pharmacopeia
[10]. Scholars such as Ibn Sina [11] and Maimonides
imprinted herbal medicine as the leading medicinal modality
at the time. Medicinal herbs are nowadays widely used in the
Middle East and as has been documented in years in Israel
[1015].
original articles
During the last two decades increasing numbers of in vitro
and clinical studies suggest the potential role of Middle-Eastern
herbs in cancer care. The former included plants such as black
cumin (Nigella sativa) [1315], fig (Ficus carica) [16], turmeric
(Curcuma longa) [17], felty germander (Teucrium polium) [18],
Boswellia dioscorides [19], Cyperus rotundus [20], and oleander
(Nerium oleander) [21]. Clinical studies involving cancer
patients included wheat grass juice (Triticum aestivum) for
chemotherapy-induced hematological toxicity in breast cancer
[22] and henna (Lawsonia inermis) for capecitabine-induced
handfoot syndrome (Yucel and Guzin, Turkey) [23]. More
studies have been reported recently [2426].
The goal of this survey was to explore the potential role of
Middle Eastern plants in cancer care by comparing historical
databases with contemporary scientific research.
methods
The present survey included family and medicine specialists, who practice
complementary and integrative medicine, four oncologists, an Islamic
medicine history specialist, a traditional medicine ethnobotanist, and
a basic research scientist.
The survey was based on a two-step research methodology:
1 Step 1: The last author identified 640 Islamic, Jewish, and other Middle
Eastern traditional medicine resources, which were mostly published
non-electronically [27]. The last author collaborated with the third
author and traced 20 resources that are electronically searchable (10 in
Hebrew and 10 in Arabic). The literature search was carried out
independently by the two researchers following defining keywords
commonly used in Middle Eastern historical and ethnobotanical
resources in relation to cancer care. Keywords such as cancer, tumor,
and lump were matched with similar words in Arabic and Hebrew. In
addition, the Medline database was searched for historical and
ethnobotanical publications by employing combinations of the following
keywords: cancer, history, ethnobotany, herb, plant, and names of
Middle Eastern countries. The findings were presented to a third
researcher independent who reviewed any disagreements encountered
between the two independent researchers (Table 1, left column).
2 Step 2: Three researchers carried out a search in PubMed focusing on
cancer-related basic and clinical research associated with herbs identified in
Step 1. The search was carried out independently for each herb by cross-
referencing its scientific name using the following keywords: cancer,
chemotherapy, in vitro, in vivo, cell culture, randomized controlled, and
epidemiology studies. Any disagreements concerning the accuracy of the
findings were presented to two other researchers for a final decision
concerning inclusion/exclusion of the reference in the list of herbs. The
latter included herbs with both historical/ethnobotanical and basic science/
clinical references as related to cancer. The basic science/clinical references
are presented in the two right hand columns of Table 1.
results
findings based on historical and ethnobotanical
sources
The historical and ethnobotanical searches included 20 sources
and yielded references for 44 herbs, of which 12 are regarded as
food (e.g. onion, figs, tea, lemon, and grapes), spices (e.g.
turmeric, cinnamon, black cumin), or seasonal fresh dishes
(e.g. stinging nettle) in various Middle Eastern cuisine. Only
212 | Ben-Arye et al.
Annals of Oncology
a small number of herbs are referenced with specific clinical
indications such as treatment of cancers in the skin (seven
herbs), mouth (three herbs), and gut (one herb) or for
nutritional support of patients with cancer (five herbs).
findings based on basic clinical studies
Of the 44 herbs cited in historical/medicinal sources, 34 herbs
were referenced in an oncological context: 8 had been studied
in both basic and clinical studies, 25 in basic research only, and
1 was examined in a clinical setting only (Table 2 specifies herbs
tested in clinical trials).
discussion
This survey attempted to target herbs for future clinical studies
based upon historical references and/or previous research. This
complies with research undertaken in countries with a rich
diversity of flora (e.g. Amazonian forest in Brazil [142]) or with
developed traditional systems of medicine (e.g. ayurvedic
medicine in India [91] and traditional Chinese medicine [143]).
This present survey revealed an important spectrum of potential
cancer-related activities by various herbs that include inhibitory
effects on angiogenesis, molecular pathways of the nuclear factor
kappaB transcription factor, epidermal growth factor receptor,
the HER2/neu gene, cyclooxygenase-2 enzyme, protein kinases,
the Bcl-2 protein, and coagulation pathways [144].
The present findings lend support to the hypothesis that
future clinical research using such herbs might contribute to
our current supportive care in cancer patients. Such research
may rely in part upon traditional observations and gain
a higher signal to noise ratio. Moreover, such studies may
shorten the laboratory time needed for species analysis.
Traditional documentation of safety and dosing can potentially
substitute phase I and II trials although this is still an issue of
ethical debate [145].
The main challenge in traditional medicine-based research is
to prioritize which herbs warrant further clinical studies. The
present survey identified herbs with potential relevance to cancer
treatment. We are well aware that in addition to the issues
searched and validated, other aspects could be considered while
evaluating the potential clinical relevance of herbs with regard to
palliation in cancer care. These include: (i) the prevalence of the
current use of an herb and the motives for its usage in a specific
community or country; (ii) safety concerns, including possible
interactions with conventional treatment; (iii) potential efficacy
in improving patients unmet needs and symptoms (e.g.
chemotherapy-related neuropathy, fatigue, cognitive
impairment, stomatitis, etc.). The present study took into
consideration these parameters and accordingly, we recommend
a further in-depth study of 4 herbs of the original 44 herb list:
citrus lemon, L. inermis (henna), C. longa (turmeric), Viscum
album (mistletoe), and Salvia species (sage).
We fully realize that the current study has significant
limitations. It is possible that the historical and ethnobotanical
search was confined to begin with, due to the definitions
(e.g. lump versus carcinoma), diagnosis (e.g. malignant versus
benign skin tumors), prevalence (e.g. more versus less prevalent
cancer types in Westernized societies), and the sites (e.g. occult
pancreatic cancer versus breast cancer invading the skin) of
Volume 23 | No. 1 | January 2012
Annals of Oncology
Table 1. Herbs referenced within an oncological context in Middle Eastern historical/ethnobotanical and basic science/clinical literature
Scientific name
(English name, family)
Allium cepa L.
(onion, Liliaceae)
Althaea officinalis
(marsh-mallow,
Malvaceae)
Amaranthus blitum
(blite; purple amaranth,
Amaranthaceae)
Anacyclus Anthemis
pyrethrum (pellitory of
Spain, Asteraceae)
Anchusa italica and officinalis
(Borage, Boraginaceae)
Arum dioscorides (spotted
arum, Araceae)
Boswellia carteri and sacra
(frankincense,
Burseraceae)
Camellia sinensis (green
tea, Theaceae)
Cephaelis ipecacuanha
(ipecac, Rubiaceae)
Cercis siliquastrum
(Judas-tree, Fabaceae)
Cinnmomum sp. zeylanicum
and cassia (cinnamon,
Lauraceae)
Citrus limon
(lemon, Rutaceae)
Volume 23 | No. 1 | January 2012
Historical/traditional source
Palestinian traditional
medicine [28]
Maimonides. (12th century,
Egypt) [37]
Maimonides. (12th century,
Egypt) [38]
al-Kind
i. (10th century, Iraq) Inhibition of tobacco-
[39]
al-Kind
i. (10th century, Iraq)
[41]
Palestinian traditional
medicine [33]
al-Qazwini. (13th century,
Iran and Iraq) [43]
Yemenite Jews traditional Apoptosis induction in
medicine [45]
Bedouin traditional medicine
[54]
al-Kind
i. (10th century, Iraq)
[41]
Rabbi Hayim Vital (1617th Suppresses tumor
century, Egypt and Israel)
[55]
Bedouin traditional medicine Limonin is P-glycoprotein
[57]
original articles
Cancer-related in Clinical studies (according Safety (including interactions
vitro studies to cancer site) with chemotherapy)
Inhibition of tumor Breast [31]
promotion in mice model Colorectal adenoma [32]
[29] Gastric [33]
Inhibition of DMBA-induced Prostate [34]
mouse skin tumorgenesis Stomach and esophagus [35]
[30] Endometrial [36]
induced mutagenesis [40]
An alkaloid derived from
Arum palaestinum Boiss
suppresses proliferation of
breast and lymphoblastic
leukemia cells [42]
Cytotoxic effect of
Frankincense oil on
bladder carcinoma cells
[38] and cytotoxic effects
on human neuroblastoma
cells [41]
Apoptosis in melanoma and
fibrosarcoma cells [44]
Cervical precancerous lesions May impair Bortezomib
prostate cells [46] [48] activity [53]
Induction of tumor Oral precancerous lesions
suppressor signaling in [49]
colorectal cancer cells [47] Prostate cancer [50, 51]
Advanced prostate cancer risk
reduction [52]
progression by modulating
angiogenesis [56]
Prostate cancer-modified
inhibitor [58] citrus pectin increases PSA
Didymin, glycoside from doubling time [57]
citrus fruits, induces
Fas-mediated apoptotic
pathway in human non-
small-cell lung cancer cells
[59]
doi:10.1093/annonc/mdr054 | 213
original articles
Table 1. (Continued)
Scientific name
(English name, family)
Citrullus colocynthis Yemenite Jews traditional
(colocynth, Cucurbitaceae)
Commiphora myrrha
(myrrh, Burseraceae)
Convolvulus scammonia
(scammony/Syrian
bindweed, Convolvulaceae)
Costus speciosus (Arabian
costus, Costaceae)
Crocus sativus
(saffron, Iridaceae)
Curcuma longa (turmeric,
Zingiberaceae)
Cyperus longus (sweet
cyperus, Cyperaceae)
Cyperus rotundus (papyrus
reed, Cyperaceae)
Dracaena draco (dragons
blood, Dracenaceae)
Ficus carica (fig, Moraceae)
Glycyrrhiza glabra (licorice,
Fabaceae)
Helleborus niger and
Helleborus albus (hellebore,
Ranunculaceae)
214 | Ben-Arye et al.
Historical/traditional source
medicine [60, 61]
al-Kind
i. (10th century, Iraq)
[41]
Bedouin traditional medicine
[57]
al-Kind
i. (10th century, Iraq)
[41]
Rabbi Hayim Vital (1617th
century, Egypt) [60]
al-Kind
i. (10th century, Iraq)
[41]
al-Samarqand
i. (1314th
century, Iran) [74]
al-Kind
i. (10th century, Iraq)
[41]
al-Kind
i. (10th century, Iraq) Antiproliferative effect in
[41]
al-Kind
i. (10th century, Iraq) Induction of apoptosis in
[41]
Rabbi Hayim Vital (1617th Suppresses proliferation of
century, Egypt) [60]
al-Kind
i. (10th century, Iraq) Angio-inhibitory activity and
[41]
Saladino dAscoli (15th Apoptosis-inducing activity
century, Italy) [82]
Annals of Oncology
Cancer-related in Clinical studies (according Safety (including interactions
vitro studies to cancer site) with chemotherapy)
Growth inhibitory activity on
human breast cancer cells
[62]
Hepeel (homeopathic remedy
that includes C.
colocynthis) induces the
antiproliferative effect on
HepG2 hepatoblastoma
cells [63]
Antiproliferative activity on
cancer cell lines [64]
Inhibition of angiogenesis
and fibrosarcoma growth
in mice [65]
Growth inhibitory effect
against various cancer cell
lines [66]
Inhibitory effects on the
growth of human
transitional cell carcinoma
[67]
Cytotoxic and apoptogenic
properties in human
cancer cells [68]
Antiproliferative effects on
human colorectal cancer
cells [69]
Growth inhibition of Colorectal cancer: safety Augments gemcitabine
colorectal cancer cells [70] bioavailability study [71] cytotoxic effect on
Pancreatic cancer [72] pancreatic
adenocarcinoma cell
lines [73]
K562 erythroleukemia cells
[26]
Antiapoptotic effect [75]
myeloid leukemia cell line
HL-60 [76, 77]
various cancer cells [22]
Antitumor effects [78, 79]
antiproliferative effects in
mice [80]
Cell cycle arrest in androgen-
independent PC-3 prostate
cancer cells [81]
in lymphoma, leukemia,
and melanoma cells [83]
Volume 23 | No. 1 | January 2012
Annals of Oncology
Table 1. (Continued)
Scientific name
(English name, family)
Hordeum sp. (barley,
Poaceae)
Lagenaria vulgaris (bottle
gourd, Cucurbitaceae)
Laurus nobilis (laurel,
Lauraceae)
Lawsonia inermis (alba)
(henna, Lythraceae)
Lepidium sativum (common
garden cress, Brassicaceae)
Moringa peregrina (ben tree,
Moringaceae)
Nerium oleander (oleander,
Apocynaceae)
Nigella sativa (black cumin,
Ranunculaceae)
Peganum harmala (wild rue,
Zygophyllaceae)
Physalis alkekengi (alkekengi/
winter cherry, Solanaceae)
Pistacia lentiscus (lentisk,
Anacardiaceae)
Plantago ovata (desert Indian
wheat, plantain, Blond
Psyllium, Plantaginaceae)
Polypodium vulgare
(polypody, Polypodiaceae)
Quercus sp. (oak resin,
Fagaceae)
Salvia sp. (sage, Lamiaceae)
Volume 23 | No. 1 | January 2012
original articles
Historical/traditional source Cancer-related in Clinical studies (according Safety (including interactions
vitro studies to cancer site) with chemotherapy)
Maimonides. (12th century, Protects from DMH-induced
Egypt) [38] intestinal tumors in rats [84]
Prevents chemo-induced
colonic carcinogenesis in
rats [85]
Maimonides. (12th century,
Egypt) [38]
Al-Brun (1011th century, Cytotoxic activity against in
Egypt) [65, 86] vitro human tumor models
[87]
Apoptosis induction [88]
Immunomodulatory and
cytotoxic activities [89]
Bedouin traditional medicine Photo-cytotoxic activity [90] Capecitabine-induced hand
[57] foot syndrome [91]
al-Kind
i. (10th century, Iraq) Chemoprotective effects in
[41] rats colon and liver cells [92]
al-Kind
i. (10th century, Iraq)
[41]
al-Kind
i. (10th century, Iraq) Inhibits activation of NF- Phase I trial of Anvirzel in
[41] kappaB and AP-1 [93] patients with refractory
solid tumors [94]
Bedouin traditional medicine Antitumor activity of
[57] gemcitabine and oxaliplatin
is augmented by
thymoquinone in pancreatic
cancer [95]
Induction of apoptosis in
HeLa cells [96]
Maimonides. (12th century, Antitumor effect in animal
Egypt) [38] studies [97] and cell lines
[98]
al-Kind
i. (10th century, Iraq) Antineoplastic activity against
[41] Ehrlich ascites carcinoma
in mice [99]
Ibn al-Bay?
ar (13th century, Apoptosis induction in
Andalusia, Middle East) human colon cancer cells
[100] [101]
Wild medicinal plants of Inverse trend between the
Egypt, 1999 [102] consumption of P. ovata
and colorectal cancer
mortality [103]
al-Kind
i. (10th century, Iraq)
[41]
al-Kind
i. (10th century, Iraq) Tyrosine-specific protein
[41] kinase inhibition [104]
Rabbi David de Silva. (18th Chemopreventive effects of Diet including salvia
century, Jerusalem) [105] sage oil on skin papillomas improved quality of life in
in mice [106] patients with advanced
Apoptosis in human colon breast cancer [108]
cancer cell lines [107]
doi:10.1093/annonc/mdr054 | 215
original articles Annals of Oncology

Table 1. (Continued)

Scientific name Historical/traditional source Cancer-related in
(English name, family) vitro studies
Urtica sp. (nettle, Urticaceae) D
awud al-?An?
ak
i [109] in Antiproliferative effect on
Turkey human prostate cancer
cells [110]
Adenosine deaminase
inhibition in prostate
tissue from cancer patients
[111]
Vicia ervilia (bitter vetch, al-Kind
i. (10th century, Iraq)
Fabaceae) [41]
Viscum album (Greek al-Kind
i. (10th century, Iraq) Induce apoptosis [113]
mistletoe, Santalaceae) [41]
Cytotoxic activity [114]
DNA repair in peripheral
blood mononuclear cells
[115]
Angiogenesis inhibition [116] Reduces malignant ascites
Antiproliferative effects in
cancer cell lines [117]
Induction of maturation and May improve survival in the
activation of human
dendritic cells [118]
Stimulates the production of May lower recurrence in
GM-CSF, IL-5, and IFN-c
[119]
Viscum cruciatum (mistletoe, Palestinian traditional Cytotoxic activity against
Linaceae) medicine [33] larynx [137], melanoma,
renal, and breast cancer cell
lines [138]
Vitis vinifera (grapevine al-Kind
i. (10th century, Iraq) Suppressed gastric [139] and
vinegar, Ampelidaceae [41] breast [140] cancer cells
Vitaceae) proliferation
Clinical studies (according Safety (including interactions
to cancer site) with chemotherapy)
Potential drugherb
interactions [112]
Improves quality of life in Potential synergism of V.
patients with [120]: Breast album lectins with
[121, 122] paclitaxel [135]
Breast, ovarian, and Systematic review reported
non-small-cell lung cancer one serious adverse event
[123] related to Viscum; mild
Reduced side-effects of adverse events were local
chemotherapy for breast reactions at injection site.
cancer [124] and side- Allergic reactions were rare
effects of radiotherapy for [136]
ear, nose, and, throat
cancer [125]
[126]
Improved health status of
patients undergoing cancer
surgery [127]
following cancer sites:
breast [128], cervix [129],
ovary [130], uterine [131],
colon [132], melanoma
[133]
superficial bladder cancer
[134]
Grape seed extract may
inhibit CYP2C9 and
CYP3A4 [141]

DMBA, 7,12-dimethylbenz[a]anthracene; GM-CSF, granulocytemacrophage colony-stimulating factor; IFN-c, interferon-c; IL-5, interleukin 5.

different cancer types reported in Middle Eastern historical
medicinal texts. Other limitations include possible inaccuracy
in identifying the herbs scientific name, language limitations
(e.g. lack of Turkish-language medicinal textbooks), and the
limited number of electronically available resources, which
include a scientific bibliography for Islamic and Middle Eastern
traditional medicine. In addition, our search is limited by the
absence of comprehensive ethnobotanical surveys focusing on
herbal use in cancer care in the Middle East.
We take in account that similar limitations related to herbal use
in cancer-associated illness emerge across cultures. An additional
possible approach promoting the usage of such herbs relates to
cancer prevention through practical inclusion of herbs in
patients daily life and cuisine, as it was customary in the Middle
East for centuries. This can be done along with the conventional
concept of pharmaceuticals and thereby gaining health-
promoting efforts while considering cultural backgrounds.
conclusions
A multidisciplinary approach combining traditional herbal
knowledge with contemporary research is a valuable
methodology for identifying potential herbs with possible
clinical significance in cancer care. We therefore propose that

216 | Ben-Arye et al. Volume 23 | No. 1 | January 2012

Annals of Oncology
Table 2. Herbs tested in clinical trials
Herb
Allium cepa (onion)
Camellia sinensis (green tea)
Citrus limon (lemon)
Curcuma longa (turmeric)
Lawsonia inermis (henna)
Nerium oleander (oleander)
Plantago ovata
Volume 23 | No. 1 | January 2012
Type of study
Casecontrol study [31]
Casecontrol study [33]
Cohort study [34]
Nested casecontrol study [35]
Casecontrol study [36]
Phase II trial [50]
Prospective cohort study [52]
Phase II trial [57]
Dose-escalation pilot study [71]
Phase II trial [72]
Case report series [23]
Phase I trial [94]
Cohort study [103]
original articles
End point
Studying the role of diet on
breast cancer risk
Studying the role of diet on
stomach cancer risk
Determining the relative
importance of dietary/
environmental risk and risk
reduction factors for prostate
cancer mortality
Association of vegetable intake,
esophagus and gastric cancer
risk
Evaluating the relationship
between onion and garlic
intake and endometrial cancer
Evaluating green tea
antineoplastic activity, as
defined by a decline in PSA
levels, among patients with
androgen-independent
prostate carcinoma
Green tea consumption and
prostate cancer risk in
Japanese men
Studying changes in the prostate-
specific antigen doubling time
in men with prostate cancer
and PSA failure after localized
treatment
Pharmacodynamics and
pharmacokinetics of curcumin
in patients with advanced
colorectal cancer
Evaluating the clinical, biological
effects, and tumor inhibitory
properties of curcumin against
advanced pancreatic cancer
Evaluating topical henna for
capecitabine-induced hand
foot syndrome (HFS)
Studying the maximum tolerated
dose and safety of Anvirzel in
patients with advanced
refractory solid tumors
Studying the association between
P. ovata consumption and
colorectal cancer mortality
rates
doi:10.1093/annonc/mdr054 | 217
Results
Breast cancer risk was shown to
decrease as consumption of
onions increased
Decrease in risk was associated
with consumption of onions
Consumption of onions is a risk
reduction factor for prostate
cancer mortality
Negative association is possible
regarding onion intake and
intestinal type gastric cancer
The overall risk of endometrial
cancer for successive categories
of onion intake were 0.94 for
<2 portions/week and 0.40 for
2 portions/week, with
a significant inverse trend in
risk
Tumor response occurred in 1/42
patients; grade 1 or 2 toxicity
occurred in 69% of patients;
seven episodes of grade 3 or 4
toxicity also reported
The multivariate relative risk of
advanced prostate cancer was
0.52 for men drinking five or
more cups/day compared with
less than one cup/day
PSA doubling time increased in 7
of 10 men after taking modified
citrus pectin for 12 months
Oral Curcuma extract was well
tolerated up to 2.2 g daily;
curcumin has low oral
bioavailability in humans
Oral curcumin is well tolerated
and has biological activity in
some patients with pancreatic
cancer
Complete response were seen in
four patients with grade 3 HFS
and all of grade 2
Anvirzel can be safely
administered at doses up to 1.2
ml/m2/day
Consumption of P. ovata tended
to be inversely correlated with
mortality from colorectal
cancer
original articles Annals of Oncology

Table 2. (Continued)

Herb Type of study End point Results

Viscum album (mistletoe)
Randomized, controlled double-
blind clinical trial [122]
Randomized, controlled open
clinical trial [123]
Phase II trial [127]
Phase I/II clinical trial [134]
Investigating the impact of
aqueous mistletoe extract on
QoL in breast cancer patients
Studying efficacy safety and side-
effects of standardized
mistletoe extract in patients
with breast, ovarian, and non-
small-cell lung cancer during
chemotherapy
Studying the efficacy of
intraperitoneal injections of V.
album in reducing the
accumulation of ascites in
digestive tract cancer
patients
Studying effect of adjuvant
intravesical treatment with
a standardized mistletoe
extract in preventing
recurrence of superficial
urinary bladder cancer
The extract was shown to be safe
and effective in improving
QoL in breast cancer patients
during chemotherapy
QoL was significantly improved
and occurrence of
chemotherapy adverse events
was less frequent in patients
who were complementarily
treated with sME in
comparison to the control
group
Installation of Iscador M into the
peritoneal cavity increased the
median time interval between
repeated punctures. No
toxicity was observed
Within the observation time of 1
year, recurrence rate of
patients treated with
intravesical viscum treatment
was comparable to that of local
historical controls who had
been treated with adjuvant
BCG

PSA, prostate-specific antigen; QoL, quality of life; sME, standardized mistletoe extract.

the Middle East could serve as a unique region for future
collaborative multicultural-oriented cancer research.
acknowledgements
We are grateful to Ms Marianne Steinmetz for editing the
manuscript.
funding
xao de Amparo a` Pesquisa do Estado de Sao Paulo
Fundac
FAPESP Process n 08/50479-2.
disclosure
The authors declare no conflicts of interest.
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