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ATUALIZAES EM

FITOTERAPIA DO CNCER
Prof. Leandro Medeiros
Farmacutico e doutorando em Inovao Teraputica | UFPE
Grupo de Pesquisas em Prticas Integrativas e Complementares | FG/Laureate International Universities
Ps-graduao em Fitoterapia: prescrio e aplicabilidade clnica | iPGS
Grupo de Trabalho em Fitoterapia | CRN6

Salvador, 2014

PROGRAMAO
1.
2.
3.
4.

Definies
Riscos da fitoterapia no cncer
Benefcios da fitoterapia no cncer
Posio do INCA quanto ao uso de
PM&F em pacientes oncolgicos
5. Busca de evidncias do uso de
fitoterpicos

DEFINIES

LEGISLAO SANITRIA
(FITOTERAPIA)

Revogadas$

RDC$14/2010$
(Registro"de"medicamentos"
toterpicos)"
RDC$10/2010$
(No6cao"de"drogas"vegetais)"
RE$90/2004"
(Guia"para"realizao"de"estudos"
de"toxicidade"pr@clnica"de"
toterpicos)"
IN$05/2010"
(Lista"de"referncias"para"
comprovao"de"segurana"e"
eccia"de"toterpicos)"
IN$05/2008"
(Lista"de"medicamentos"
de"registro"simplicado)"

RDC"26/2014"

(Registro"de"medicamentos"
toterpicos"e"o"registro"e"a"no6cao"
de"produtos"tradicionais"toterpicos)"

IN"02/2014"

(Lista"de"medicamentos"
toterpicos"de"registro"simplicado"e"
a"lista"de"produtos"tradicionais""
toterpicos"de"registro"simplicado)"2"

PLANTAS"MEDICINAIS"
(Lei"5991/1973)"

Uso"no"medicinal"

Chs"
alimenLcios"

DROGAS"VEGETAIS"
Uso"medicinal"

DERIVADO(VEGETAL(
(EXTRATOS)(

(RDC(27/2010;(
RDC(219/2006;(
RDC(267/2005;(
RDC(277/2005(

Chs"
medicinais"

FITOTERPICO(

MANIPULADO"

(
FARMCIAS(DE(
MANIPULACO(
(RDC"67/2007"/"
87/2008)"

Uso"medicinal"

FARMCIAS(
VIVAS((RDC"
18/2013)"

(RDC"26/2014)"

INDUSTRIALIZADO(

MEDICAMENTO(
FITOTERPICO(
(REGISTRO"COMUM"
OU"SIMPLIFICADO)"

(RDC"26/2014)"

PRODUTO(
TRADICIONAL(
FITOTERPICO(
(REGISTRO"
SIMPLIFICADO"OU"
NOTIFICADO)"
(RDC"26/2014"e" 3"
IN"02/2014)"

LISTA*DE*MEDICAMENTOS*FITOTERPICOS*DE*REGISTRO*SIMPLIFICADO*

IN*05/2008*
Nomenclatura!botnica!! Allium!sa)vum!L.!
Nome!popular!!
Alho*
Parte!usada!!
Bulbo!
Padronizao/Marcador!!Alicina!
Derivado!de!droga!
Extratos/)ntura/leo!
vegetal!!!
2*
Coadjuvante!no!tratamento!da!
hiperlipidemia!e!hipertenso!
Indicaes/Aes!
arterial!leve,!auxiliar!na!
terapu)cas!!
preveno!da!aterosclerose!!
Dose!Diria!!
2,7!a!4,1!mg!de!alicina!
Via!de!Administrao!! Oral!
Restrio!de!uso!!
Venda!sem!prescrio!mdica!

IN*02/2014*
Allium!sa)vum!L.!
Alho*
Bulbo!
Alicina!
Extratos/leos!
Coadjuvante!no!tratamento!da!
hiperlipidemia!e!hipertenso!arterial!
leve,!auxiliar!na!preveno!da!
aterosclerose!!
3!a!5!mg!de!alicina!
Oral!
Venda!sem!prescrio!mdica!

10!

LISTA*DE*MEDICAMENTOS*FITOTERPICOS*DE*REGISTRO*SIMPLIFICADO*
IN*05/2008*
Nomenclatura!
botnica!!
Nome!popular!!
Parte!usada!!
Padronizao/
Marcador!!
Derivado!de!droga!
23* vegetal!!!
Indicaes/Aes!
terapu)cas!!
Dose!Diria!!
Via!de!
Administrao!!
Restrio!de!uso!!

IN*02/2014*

Tanacetum!parthenium!Sch.!Bip.!! Tanacetum!parthenium!(L.)!Sch.!Bip.!!
Tanaceto*
Folhas!

Tanaceto*
Folhas!

Partenoldeos!

Partenoldeos!

Extratos/)ntura!

Extratos/)ntura!

Prolaxia!da!enxaqueca!

Prolaxia!da!enxaqueca!

0,2!a!0,6!mg!de!partenoldeos!

0,2!a!0,6!mg!de!partenoldeos!

Oral!

Oral!

Venda!sob!prescrio!mdica.!No! Venda!sob!prescrio!mdica.!No!usar!de!
usar!de!forma!concnua.!
forma!concnua.!

31!

LISTA*DE*PRODUTOS*TRADICIONAIS*FITOTERPICOS*DE*REGISTRO*SIMPLIFICADO*
IN*05/2008*
Nomenclatura!
botnica!!
Nome!popular!!
Parte!usada!!
Padronizao/
Marcador!!
Derivado!de!droga!
8* vegetal!!!

IN*02/2014*

Maytenus!ilicifolia!Mart.!ex!Reiss.!! Maytenus!ilicifolia!Mart.!ex!Reiss.!!
Espinheiradsanta*
Folhas!

Espinheiradsanta*
Folhas!

Taninos!totais!

Taninos!totais!expressos!em!pirogalol!

Extratos/)nturas!

Extratos/)nturas!

Alegao!de!uso!

Dispepsias,!coadjuvante!no!
tratamento!de!gastrite!e!lcera!
gastroduodenal!!

Dispepsias,!coadjuvante!no!tratamento!de!
gastrite!e!lcera!gastroduodenal!!

Dose!diria!

60!a!90!mg!taninos!totais!!

Via!de!Administrao!!Oral!
Restrio!de!uso!!
Venda!sem!prescrio!mdica.!

60!a!90!mg!taninos!totais!expressos!em!
pirogalol!
Oral!
Venda!sem!prescrio!mdica.!

43!

CHS MEDICINAIS

Substitui o termo droga vegetal notificado


Drogas vegetais com fins medicinais a serem
preparadas por infuso, decoco ou macerao pelo
consumidor
Entram na categoria de produto tradicional fitoterpico
No podem conter excipientes em suas formulaes
(apenas drogas vegetais)

PRESCRIO DE FITOTERPICOS
POR NUTRICIONISTAS
CFN | RE 525/2013
Isentos de prescrio mdica
Exclusivamente por via oral
No associado a substncias bioativas, mesmo que de origem
vegetal, ou ainda a nutrientes
Relacionados com o campo de atuao do nutricionista
Baseados em evidncias cientficas ou na tradicionalidade de uso

CARACTERSTICA DOS
FITOTERPICOS
430

430

Milk Thistle

Milk Thistle
430

Milk Thistle

ilk Thistle

esis and acceleration of liver regeneration. Silymarin (an isomer


mixture comprising mainly silibinin, silichristin and silidianin) is
the pharmacologically active component of milk thistle fruit;
silibinin is the main component of silymarin. There is an extensive
literature on the pharmacological effects of silymarin and
silibinin, particularly with regard to their hepatoprotective
activity which provides supporting evidence for the clinical uses.
The pharmacology and clinical efficacy of milk thistle have been
reviewed.(13, G50, G55) The following represents a summary of
selected publications on this subject.
There is a lack of research investigating the pharmacological
effects of preparations of milk thistle leaf.(G2, G32, G35)

Figure 1 Selected constituents of milk thistle.

In vitro and animal studies


Dosage
Dosages for oral administration (adults) for traditional uses

Antioxidant activity recommended


Silymarin and
silibinin
are are given below.
in standard
herbal(silybin)
reference texts
antioxidants that react with free radicals (e.g. reactive oxygen
Fruit Crude drug 1215 g daily in divided doses (equivalent to
species) transforming them
into 200400
more mg
stable
and
(G3) less reactive
silymarin
daily).
(1, 46)
compounds.
Silymarin and silybin have been reported to
Herb Approximately 1.5 g of finely chopped material as a tea, two
inihibit lipid peroxidation
induced by iron-linked systems in rat
or three cups daily.
(7, 8)
and protect against phenylhydrazine-induced
liver microsomes

esis and acceleration of liver regeneration. Silymarin (an isomer


mixture comprising mainly silibinin, silichristin and silidianin) is
the pharmacologically active component of milk thistle fruit;
Figure
2 Milk
thistleof(Silybum
silibinin
is the main
component
silymarin.marianum).
There is an extensive
literature on the pharmacological
effects ofmarianum
silymarin and
Silybum
silibinin, particularly with regard to their hepatoprotective
low-density lipoproteinevidence
(LDL)for in
vitro in a
activity which provides supporting
the clinical uses.
(10)
dependent and
manner.
Silybin
appears
to be
The pharmacology
clinical efficacy
of milk
thistle have
beenthe
(13, G50, G55)
reviewed.
The following represents a summary of

concentration
constituent o

RISCOS

The use of at least one type of CT at the time


of the interview was reported by 37.9% of patients. In the past, 75.2% of the patients had
used CTs. Several demographic and clinical
factors were shown to be associated with the
current and previous use of CT. Younger, female and well-educated patients were more

CARACTERSTICAS
POPULACIONAIS DE TERAPIAS
COMPLEMENTARES NO CNCER
Uso de fitoterpicos
utilizados durante ou do
tratamento convencional
Usurios mais frequente:
mulheres, jovens, com bom
nvel de escolaridade
(p<0,001)

Table 2
Present and Past Use of CTs
Present
Use of
CTs
Types of CTs
Diets and dietary supplements
Diets
Dietary supplements
Mind-body therapies
Yoga
Meditation
Autogenic training
Others types of mind-body
therapies less commonly used
Unconventional cancer treatment
Other types of CTs
Herbs
Homeopathy
Acupuncture
Bach flowers
Massage
Other types of CTs less
commonly used
Total users of at least one CT
CT complementary therapy.

Bonacchi et al., 2014

Past
Use of
CTs
n

221 27.5 504 62.8


46 5.7 252 31.4
193 24.0 372 46.3
44 5.5 169 21.0
19 2.4 106 13.2
16 2.0 43 5.4
16 2.0 76 9.5
11 1.4 27 3.4
10 1.2 d d
161 20.0 406 50.6
87 10.8 172 21.4
51 6.4 183 22.8
8 1.0 127 15.8
12 1.5 97 12.1
24 3.0 152 18.9
27 3.4 123 15.3
304 37.9 604 75.2

The study received the approval of the local


ethics committees of Careggi Hospital, of
AUSL 10 in Florence, of AUSL 4 in Prato
and of AUSL 1 in Massa Carrara. Patients
gave written informed consent and received
an information sheet on the study.

a high percentage of patients informed their


physicians about CT use (66.3%), and almost
all relatives (95.3%) were aware of CT use.

CARACTERSTICAS
POPULACIONAIS DE TERAPIAS
COMPLEMENTARES
NO CNCER
Results

Independent Predictors of CT Use at the Time


of the Study
Using logistic regression analysis, we evaluated the independent association of each

Use of CTs
The use of at least one type of CT at the time
of the interview was reported by 37.9% of patients. In the past, 75.2% of the patients had
used CTs. Several demographic and clinical
factors were shown to be associated with the
current and previous use of CT. Younger, female and well-educated patients were more

Prevalncia do uso de
prticas integrativas e
complementares em sade:
Table 2

Present and Past Use of CTs

Europa (35,9%)
Types of CTs
Diets and dietary supplements
Diets
Dietary supplements
Mind-body therapies
Yoga
Meditation
Autogenic training
Others types of mind-body
therapies less commonly used
Unconventional cancer treatment
Other types of CTs
Herbs
Homeopathy
Acupuncture
Bach flowers
Massage
Other types of CTs less
commonly used
Total users of at least one CT

Alemanha (35%)
Itlia (75,2%)

Bonacchi et al., 2014

CT complementary therapy.

Present
Use of
CTs
n

Past
Use of
CTs
n

221 27.5 504 62.8


46 5.7 252 31.4
193 24.0 372 46.3
44 5.5 169 21.0
19 2.4 106 13.2
16 2.0 43 5.4
16 2.0 76 9.5
11 1.4 27 3.4
10 1.2 d d
161 20.0 406 50.6
87 10.8 172 21.4
51 6.4 183 22.8
8 1.0 127 15.8
12 1.5 97 12.1
24 3.0 152 18.9
27 3.4 123 15.3
304 37.9 604 75.2

Table 3
Characteristics of the Present Use of CTs
(N 196)

Users of CTs
N

Reasons for using CTs (more than one possible option)


To improve general health conditions
118
60.5
To support medical treatments
69
35.4
To treat physical symptoms
46
23.6
To treat psychological distress
23
11.8
To treat cancer
23
11.8
Other reasons
10
5.1
Perceived benefits
Excellent
36
18.9
Good
80
41.9
Fairly good
55
28.8
Poor
13
6.8
Absent
7
3.7
Sources of information (more than one possible option)
Physician
82
42.0
Friends
61
31.3
Relatives
36
18.5
Mass media
26
13.3
Pharmacist
8
4.1
Other patients
5
2.6
Other
12
6.1
Physician informed about the use of CTs
Yes
128
66.3
No
65
36.7
Relative knowledge about the use of CTs
Yes
181
95.3
No
9
4.7
Annual cost for CTs
<250 Euro
116
60.7
>250 and <500 Euro
51
26.7
>500 and <1000 Euro
20
10.5
>1000 Euro
4
2.1
CT complementary therapy.

MOTIVOS PARA O USO DE PM&F


NO CNCER PELOS PACIENTES
VOLUME

22

NUMBER

12

JUNE

15

2004

JOURNAL OF CLINICAL ONCOLOGY

R E V I E W

A R T I C L E

Herbal Remedies in the United States: Potential Adverse


Interactions With Anticancer Agents
Alex Sparreboom, Michael C. Cox, Milin R. Acharya, and William D. Figg
From the Clinical Pharmacology Research Core, Medical Oncology Clinical
Research Unit, Center for Cancer Research, National Cancer Institute, Bethesda, MD.

Purpose
Interest in the use of herbal products has grown dramatically in the Western world. Recent estimates
suggest an overall prevalence for herbal preparation use of 13% to 63% among cancer patients. With
the narrow therapeutic range associated with most anticancer drugs, there is an increasing need for
understanding possible adverse drug interactions in medical oncology.

Insatisfao de terapias convencionais alopticas

Submitted August 27, 2003; accepted


December 2, 2003.

Address reprint requests to Alex


Sparreboom, PhD, Clinical Pharmacology Research Core, Medical Oncology
Clinical Research Unit, National Cancer
Institute, 9000 Rockville Pike, Bldg 10,
Room 5A01, Bethesda, Maryland
20892; e-mail: sparreba@mail.nih.gov.

Methods
In this article, a literature overview is provided of known or suspected interactions of the 15 best-selling
herbs in the United States with conventional allopathic therapies for cancer.
Results
Herbs with the potential to significantly modulate the activity of drug-metabolizing enzymes (notably
cytochrome P450 isozymes) and/or the drug transporter P-glycoprotein include garlic (Allium sativum),
ginkgo (Ginkgo biloba), echinacea (Echinacea purpurea), ginseng (Panax ginseng), St Johns wort
(Hypericum perforatum), and kava (Piper methysticum). All of these products participate in potential
pharmacokinetic interactions with anticancer drugs.

Maior pr-atividade dos pacientes no autocuidado

0732-183X/04/2212-2489/$20.00
DOI: 10.1200/JCO.2004.08.182

Conclusion
It is suggested that health care professionals and consumers should be aware of the potential for
adverse interactions with these herbs, question their patients on their use of them, especially among
patients whose disease is not responding to treatments as expected, and urge patients to avoid herbs
that could confound their cancer care.

Orientaes filosficas dos pacientes


J Clin Oncol 22:2489-2503.

INTRODUCTION

In recent years, interest in complementary and


alternative medicine (CAM) has grown rapidly in the industrialized world. The National
Center for Complementary and Alternative
Medicine defines CAM as a group of diverse
medical and health care systems, practices, and
products not considered part of conventional
medicine. Biologically based therapies in

or phytomedicine (botanic supplements


used as medicine). Factors contributing to
this increase are dissatisfaction with conventional allopathic therapies, patients
desire to be more active in their own
health care, and patients philosophical
orientations.1,2 It is estimated that up to
one third of the entire population in the
United States used CAM in the last 12
months; the majority of those individuals
3-5

Sparreboom et al., 2004

CARACTERSTICAS
POPULACIONAIS DE TERAPIAS
COMPLEMENTARES NO CNCER
Herb-Drug Interactions

Table 2. Prevalence of Complementary and Alternative Medicine Use Among Cancer Patients
Main Treatment

Disease

No. of
Patients

Method

Prevalence (%)

Comments

Reference

38% users had confidence in


CAM
40% of patients abandoned
conventional therapy for CAM
CAM mostly used in conjunction
with conventional medicine
Younger patients more likely to
use CAM
Prevalence in females (76%)
compared with males (58%)
23% used megavitamins
50% used vitamins; overall CAM
use was 67%
Overall CAM use was 48%
Overall CAM use was 75%
Overall CAM use was 83%;
77% combined herbals with
conventional medicines; 36%
did not inform physicians
87% used vitamins
Overall CAM use was 65%
24% did not inform physicians
Overall CAM use was 37%
Overall CAM use was 43%;
72% did not inform physician

16

Herbs, vitamins, diet

Various

151

Interview

CAM: males, 56; females, 30

Herbs, vitamins, diet

Various

304

Interview

Herbs, vitamins, diet

Ovarian cancer

295

Questionnaire

CAM: Patients on
conventional therapy, 54
CAM since diagnosis

Herbs, homeopathy, diet

Various

300

Questionnaire

52% used CAM

Chinese medications

Various

100

Questionnaire

64% used CAM

Herbal medicine, vitamins


Herbal medicine, vitamins

Breast cancer
Breast cancer

112
411

Interview
Questionnaire

14% used herbal therapy


25% used herbal therapy

Herbal medicine
Herbal medicine
Herbal medicine, vitamins

Breast cancer
Various
Breast cancer

379
617
453

Interview
Questionnaire
Questionnaire

14% used herbal therapy


44% used herbal therapy
63% used herbal therapy

Herbal medicine, vitamins


Herbs, vitamins, diet
Herbs, vitamins, diet
Herbal medicine, vitamins
Herbal medicine, vitamins

Breast cancer
Breast cancer
Prostate cancer
Prostate cancer
Prostate cancer

763
236
268
50
190

Questionnaire
Questionnaire
Questionnaire
Interview
Questionnaire

49% used herbal therapy


20% used herbal therapy
Up to 80% used CAM
22% used herbal therapy
13% used herbal therapy

Abbreviation: CAM, complementary and alternative medicine.

17
18
19
20
21
2
22
23
8

24
25
26
27
28

Sparreboom et al., 2004

VISO GERAL DA
FARMACOLOGIA
Farmacodinmica
Farmacocintica

Administrao,
desintegrao,
liberao e
dissoluo

Absoro

Metabolismo
(desativao-ativao)

Distribuio

Fase I
Oxidao/Reduo/
Hidrlise
Fase II
Conjugao do frmaco
com substncias
endgenas

Interao com protenas


no sangue

Tecido armazenador

Interao
frmacoreceptor no
tecido alvo

Excreo
Moura e Reis, 2002

MECANISMOS GERAIS DE
INTERAES ENTRE FITOQUMICOS
E QUIMIOTERPICOS
Sparreboom et al

Alteraes farmacocinticas

Alteraes no transporte pela


membrana
Aumento do transporte pela mucosa

Fig
sible
antica
duce
P450
port b
prote
the in

intestinal

Aumento do transporte pela


membrana canalicular da bile

Alteraes metablicas
Induo ou inibio enzimtica das
isoenzimas do citocromo p450

complex leading to autocatalytic destruction.58 However,


of CYP3A4
more likely, to m
Sparreboom
et al.,but,
2004
long-term administration (eg, ! 6 weeks) led to enhanced
of another (unknown) enzyme
52,59,60
activity and increased expression of CYP1A, CYP2B,
although an interaction at the l
61

48

EUA: 100.00 mortes/ano causados por interaes


medicamentosas (4 a 6 no ranking de causa de
morte total)
Parte destas mortes so atribudas a interaes
erva-medicamento

Lazarou et al., 1998


Zhou et al., 2003

FITOTERPICOS MAIS
UILIZADOS NOS E.U.A.
Sparreboom et al

Table 1. Top-Selling Herbal Supplements in the United States


2002 Rank
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15

Herb
Garlic
Ginkgo
Echinacea
Soy
Saw palmetto
Ginseng
St. Johns wort
Black cohosh
Cranberry
Valerian
Milk thistle
Evening primrose
Kava
Bilberry
Grape seed

Plant Name

Primary Clinical Indications

Retail Sales in 2002!


($US)

Allium sativum
Ginkgo biloba
Echinacea purpurea
Glycine max
Serenoa repens
Panax ginseng
Hypericum perforatum
Actaea racemosa
Vaccinium macrocarpon
Valeriana officinalis
Silybum marianum
Oenothera biennis
Piper methysticum
Vaccinium myrtillus
Vitis vinifera

Hypercholesterolemia
Dementia, intermittent claudication
Prevention of common cold
Menopausal symptoms
Benign prostate hyperplasia
Physical and mental fatigue
Mild depression
Menopausal symptoms
Urinary tract infection
Insomnia, stress
Alcoholic cirrhosis and hepatitis
Premenstrual syndrome
Anxiety
Diabetic retinopathy
Allergic rhinitis

34,509,288
32,998,528
32,448,966
28,252,518
23,053,036
21,686,192
14,969,575
12,333,188
11,857,782
8,120,329
7,762,350
6,024,896
4,423,427
3,381,351
3,054,816

2001 Rank
3
1
2
5
6
4
7
10
9
8
12
13
11
15
14

Data obtained from Blumenthal12.


Other species include E. angustifolia, and E. pallida.
Formerly Cimicifuga racemosa.
!

The major cause of the concern is the potential for


herbs to interact with prescription drugs, altering their

Sparreboom et al., 2004

than individuals with other types of malignancy,23 presumably because more women than men use CAMs.6,29,30

FITOTERPICOS NO
RECOMENDADOS DURANTE A
QUIMIOTERAPIA
Herb-Drug Interactions

Table 7. Specific Herbal Remedies to Discourage and Avoid During Chemotherapy


Herb
Garlic
Ginkgo

Echinacea
Soy
Saw palmetto
Ginseng

St. Johns wort


Black cohosh
Cranberry
Valerian
Milk thistle
Evening primrose
Kava

Bilberry
Grape seed

Concurrent Chemotherapy/Condition (suspected effect)


Avoid with decarbazine (CYP2E1 inhibition); caution with other concurrent chemotherapy (inconclusive data)
Caution with camptothecins, cyclophosphamide, EGFR-TK inhibitors, epipodophyllotoxins, taxanes, and vinca alkaloids (CYP3A4
and CYP2C19 inhibition); discourage with alkylating agents, antitumor antibiotics, and platinum analogues
(free-radical scavenging)
Avoid with camptothecins, cyclophosphamide, EGFR-TK inhibitors, epipodophyllotoxins, taxanes, and vinca alkaloids
(CYP3A4 induction)
Avoid with tamoxifen (antagonism of tumor growth inhibition), and treatment of patients with estrogen-receptor positive breast
cancer and endometrial cancer (stimulation of tumor growth)
No significant interactions expected
Caution with camptothecins, cyclophosphamide, EGFR-TK inhibitors, epipodophyllotoxins, taxanes, and Vinca alkaloids (CYP3A4
inhibition); discourage in patients with estrogen-receptor positive breast cancer and endometrial cancer (stimulation of
tumor growth)
Avoid with all concurrent chemotherapy (CYP2B6, CYP2C9, CYP2C19, CYP2E1, CYP3A4, and P-glycoprotein induction)
No significant interactions expected
No significant interactions expected
Caution with tamoxifen (CYP2C9 inhibition), cyclophosphamide, and teniposide (CYP2C19 inhibition), cyclophosphamide, and
teniposide (CYP2C19 inhibition)
No significant interactions expected
No significant interactions expected, but caution with highly extracted drugs (serum-binding displacement)
Avoid in all patients with pre-existing liver disease, with evidence of hepatic injury (herb-induced hepatotoxicity), and/or in
combination with hepatotoxic chemotherapy; caution with camptothecins, cyclophosphamide, EGFR-TK inhibitors,
epipodophyllotoxins, taxanes, and vinca alkaloids (CYP3A4 induction)
No significant interactions expected
Caution with camptothecins, cyclophosphamide, EGFR-TK inhibitors, epipodophyllotoxins, taxanes, and vinca alkaloids (CYP3A4
induction), and with alkylating agents, antitumor antibiotics, and platinum analogues (free-radical scavenging)

Abbreviation: EGFR-TK, epidermal growth factor receptor tyrosine-kinase.

Sparreboom et al., 2004

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INTERAES ERVA-MEDICAMENTO NA
QUIMITERAPIA

REVIEW ARTICLE

EVIDENCE-BASED MANAGEMENT OF HERB-DRUG INTERACTION


IN CANCER CHEMOTHERAPY
Chung-Wah Cheng, Mphil,1 Wing Fan, Mphil,1 Seong-Gyu Ko, MD, PhD, MPH,2 Lisa Song, MSc, MLib,3 and
Zhao-Xiang Bian, PhD1#

The fact that many cancer patients take herbal medicine,


including Chinese herbal medicine, together with chemotherapy is well known. The potential for side effects resulting
from concurrent use of these two different treatment modalities requires physicians to be aware of the potential risks and
benefits that might arise. This study searched available evidence for herb-drug interaction in cancer therapy and identified 168 articles. Little direct evidence for such interaction
could be found, whereas there is some indirect evidence for
benefit. Hence, most of the concern about herb-drug interaction in chemotherapy appears to be theoretical. To resolve
this discrepancy, evidence-based studies should be under-

taken to document the positive and/or negative effects of the


concomitant use of herbs with anticancer chemotherapeutic
drugs. As evidence accumulates, it would be helpful to set up
an internationally accessible database to document the use of
Chinese medicine herbs with anticancer drugs. Once this
information is collected, efforts should be made to educate
health care professionals and patients about the use of Chinese herbal medicine together with Western drugs in treating
cancer.
Key words: Chinese herbal medicine, cancer, chemotherapy,
interaction
(Explore 2010; 6:324-329. 2010 Elsevier Inc. All rights reserved.)

Cheng et al., 2010


INTRODUCTION
An increasing tendency for the use of herbal remedies as one

istered individually. The greater the number of drugs involved,


the greater the potential for drug-drug interaction. These inter-

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Clinical practices guidelines | American College
of Chest Physicians
Alerta para avaliao da relao risco/benefcio da interao potencial.
As interaes que apresentam potencial efeitos adversos negativos
devem ser evitados durante a quimioterapia
No foram mencionadas, claramente, recomendaes de uso
teraputico de fitoterpicos em caso de evidncias positivas de
benefcios
Cheng et al., 2010

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Editoriais (n = 2)
Mostram, de forma sutil, potenciais benefcios do uso de fitoterpicos
concomitantemente com a quimioterapia e a valorizao das prticas
integrativas e complementares em sade e seu impacto na qualidade de
vida dos indivduos
Porm no sugerem uma estratgia sobre o manejo mdico em caso de
uso concomitante

Cheng et al., 2010

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Artigos de reviso (n = 15)
Quase todos abordam aspectos negativos das interaes potenciais entre fitoterpicos e quimioterpicos,
seus mecanismos e efeitos (a maioria destes, baseados em dados pr-clnicos)
Enfatizam a necessidade de:
Melhorar a comunicao mdico-paciente, quanto ao uso de fitoterapia durante a QT
Os mdicos devem estar cientes das interaes erva-medicamento e discutir com o paciente a respeito
Mais estudos clnicos e pr-clnicos devem ser realizados no intuito de aumentar o corpo de evidncias
sobre o tema
Questionar o paciente quanto ao uso de fitoterpicos e propor aos pacientes evitar seu uso durante a QT
Autoridades sanitrias devem regulamentar melhor os fitoterpicos (fcil acesso nos EUA)

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Estudos epidemiolgicos (n = 6)
Evidncias de interaes negativas
Risco de alteraes farmacocinticas em quimioterpicos
Em especial, com o alho, ch verde, noni (mais frequentes)

Cheng et al., 2010

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Limitaes metodolgicas para recomendaes na prtica clnica
Ausncia de estudos avaliando associaes de extratos (frequentemente utilizadas pela
Medicina Tradicional Chinesa)
Estudos experimentais ainda inconclusivos para gerar evidncias quanto
recomendao de uso e insero em guidelines/protocolos/consensos.
Risco de alteraes farmacocinticas em quimioterpicos, em especial, m especial, com
o alho, ch verde, noni (mais frequentes)
Recomendao de aes de educao em sade na populao, sobre os riscos do uso de
fitoterpicos durante a QT

Cheng et al., 2010

BENEFCIOS

EFEITOS QUIMIOPREVENTIVOS
DOS COMPOSTOS FITOQUMICOS
180

JONATHAN TREASURE

FIGURE 4. Chemopreventive dietary compounds.

precisely the molecular targets that scientists seek


to affect with the newer generation targeted

Treasure, 2005

eradicate a cancer. In fact, cancer evades immune


system surveillance because of the low immuno-

EFEITOS BENFICOS POTENCIAIS


DOS FITOQUMICOS NA
QUIMIOTERAPIA
HERBAL MEDICINE AND CANCER

181

FIGURE 5.

Molecular targets of
chemopreventive compounds.

Treasure, 2005
of the normalizing properties of adaptogens,

en*). Immune system re-education (phase 4) is

BENEFCIOS
leo de coco na mucosite oral induzida por
metotrexato em crianas (HUOC/PE)
Gengibre no tratamento de nuseas induzidas por
quimioterapia (Natural Standard: nvel de
evidncia B)

BENEFCIOS
Recuperao de feridas induzidas por
radioterapia
Aloe vera
Camomila
Calndula
http://www.med.nyu.edu/

INCA
No recomenda o uso de plantas medicinais e
fitoterpicos por pacientes oncolgicos
Estudos clnicos de metodologia questionvel
Incerteza quanto relao risco/benefcio
Risco: interaes farmacolgicas de QT
Pouco controle quanto ao cultivo, manejo, plantio
INCA, 2011

BUSCA DE
EVIDNCIAS
SOBRE USO DE
FITOTERPICOS

www.periodicos.capes.gov.br

http://www.bireme.br/

http://www.ncbi.nlm.nih.gov/pubmed

http://www.tripdatabase.com/

http://www.medscape.com/pharmacists

https://naturalmedicines.therapeuticresearch.com/

http://nccam.nih.gov/

http://examine.com/

CONCLUSES

Obrigado!

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