Professional Documents
Culture Documents
DOI 10.1007/s00520-004-0598-1
Jeannine S. McCune
Amy J. Hatfield
Anne A. R. Blackburn
Patricia O. Leith
Robert B. Livingston
Georgiana K. Ellis
ORIGINAL ARTICLE
Abstract Goals of work: The purpose of this study was to examine the
specific herbs or vitamins (HV) used
by patients receiving chemotherapy.
Specifically, the following aspects
were investigated: (1) HV use among
adult cancer patients receiving chemotherapy, (2) the frequency of potential chemotherapyHV interactions, (3) communication patterns
between oncologists and their cancer
patients taking HV, and (4) patients
reactions to two hypothetical scenarios of chemotherapyHV interactions. Patients and methods: Adult
cancer patients receiving chemotherapy at a university-based outpatient
clinic over a 1-month period were
sent a validated eight-page questionnaire regarding the use of complementary/alternative medicine, focusing on HV use. A total of 76 patients
participated; relevant medical information was obtained from study participants charts. The chemotherapy
received was compared with HV use
to assess for potentially detrimental
Introduction
Concern over adverse interactions between herbal supplements and vitamins (HV) and prescription medications
has substantially increased in parallel with the everincreasing use of complementary alternative medicine
(CAM) in the United States [8, 9, 11, 24]. The need to
identify patients at risk for adverse interactions between
HV and prescription medications is perhaps greatest for
patients receiving chemotherapy agents, which have a
chemotherapyHV interactions.
Results: HV use in patients receiving
chemotherapy was common (78%),
with 27% of the study participants
being at risk of a detrimental chemotherapyHV interaction. Most patients (>85%) would discontinue their
HV or ask their medical oncologist
for advice if a detrimental chemotherapyHV interaction was suspected. Although most patients discussed
HV use with their oncologist, the
majority also relied on their friends
and naturopathic physician for information regarding HV. Conclusions:
Considerable potential exists for
detrimental chemotherapyHV interactions. Methods to improve communication of HV use between cancer patients receiving chemotherapy
and health-care practitioners are necessary to identify and minimize the
risk of these interactions.
Keywords Interaction
Chemotherapy Herb Vitamin
Cancer
455
456
Folate
Garlic
Ginger
Ginkgo biloba
Ginseng
Glucosamine
Glutamine
Goldenseal
Grapeseed
Green tea extract
Hydrazine sulfate
Kava kava
Kelp
Lecithin
Magnesium
Melatonin
Milk thistle
Mistletoe/iscador
Multivitamin
Mushroom
PC-SPES
Pokeroot
Potassium
Psyllium seed
Pycogenol
Quercetin
Saw palmetto
Selenium
Shark cartilage
St. Johns wort
Valerian
Vitamin A
Vitamin B12
Vitamin B6
Vitamin C
Vitamin E
Wormwood
Zinc
several questions focused upon CAM use over the previous 30 days,
including the frequency of drinking teas (i.e., black, chapparal,
essiac, green, pau DArco, taheebo, willow), the use of CAM prior
to cancer diagnosis, and the rationale for CAM use. Subsequently,
57 selected HV therapies (Table 1) were listed and spaced to allow
the patient to describe the dose, frequency of administration, and
perceived benefit for each HV. Space was also allowed for
participants to write in HV that they used but were not included in
the list. The questionnaire also addressed patients resources for
information about HV, frequency of communication with their
oncology professionals, and potential barriers to communication
regarding HV use. Two hypothetical scenarios based on cyto-
457
Efficacy
a
Level
Direction of evidence
Vitamin A
Inconclusive
Vitamin C
Not effective
III
Inconclusive
Level of risk
Reasonable advice
Discourage and
monitor
Discourage and
monitor
Discourage and
monitor
Adapted from Weiger et al. [37] Table 2, with permission. From criteria of the U.S. Preventive Task Force: I evidence obtained from at
least one properly designed randomized clinical trial, III opinions of respected authorities, based on clinical experience, descriptive studies
or reports of expert committees
Statistical analysis
Microsoft Excel was used for data entry and to calculate frequencies of participant responses; SPSS 9.0 was used for statistical
analysis. Differences between participants and non-participants
with respect to demographic characteristics (gender, race) were
assessed by chi-squared analysis and age was assessed using
Kruskal-Wallis. The demographic characteristics of users and nonusers of herbal and vitamin therapies were not compared because of
the low number of non-users accrued (n=13).
Results
The demographic characteristics, along with cancer diagnosis and treatment, for the 76 participants are presented
in detail in Table 3. The median age was 52 years (range
3083 years). Most of the participants were women (59)
and Caucasian (73). The demographic characteristics
between participants and non-participants were similar in
respect of age and gender, but not in respect of race. Most
of the study participants had normal liver and renal
function based on review of their medical records, with
one patient having a serum creatinine greater than 1.5 mg/
dl, and all patients liver function tests being less than two
times the upper limit of normal. Serum albumin was low
(<1.5 mg/dl, the lower limit of normal within the
458
76
17
59
52
3083
73
1
2
3
21
34
17
1
22
21
24
9
43
5
5
5
4
3
3
2
2
1
1
1
1
43
10
11
15
6
1
a
special
b
56
25
23
5
2
36
14
0
4
20
2
0
2
126
53 (70%)
17 (22%)
34
25
16
15
15
(45%)
(33%)
(21%)
(20%)
(20%)
3 (4%)
14 (19%)
4 (6%)
26
16
15
11
7
5
2
6
3
(34%)
(21%)
(20%)
(14%)
(9%)
(7%)
(3%)
(8%)
(5%)
a
Described in Table 2
b
Garlic, feverfew, dong
c
quai, gingko
Reported use of garlic or St. Johns wort from among 56
participants receiving chemotherapy metabolized by cytochrome
P450 [19, 27]
(57%)
(13%)
(14%)
(20%)
( 8%)
(<1%)
(73%)
(32%)
(30%)
(6%)
(3%)
(47%)
Patients were asked to rate the perceived benefit (extremely beneficial, somewhat beneficial, not beneficial at
all and dont know) of each specific HV therapy used:
61% reported that they did not know whether their HV
therapies were beneficial for them, 18% responded that
their HV use was extremely beneficial, whereas only one
participant (<1%) felt that there was no benefit.
To the question have you used herbal or vitamin
therapies during the 30 days prior to completing the
questionnaire?, 37 (49%) replied yes. However, 59
participants (78%) reported the use of at least one HV of
57 listed products. In addition, participants were allowed
to handwrite additional HV products they used that were
not included in the list. Table 5 is a detailed description of
the reported use of HV. The majority of participants (53)
used vitamins, while 17 used herbal therapies. Most
(91%) of the HV use was daily.
To estimate the number of potential interactions
between conventional medications (i.e., chemotherapy,
supportive care medications, and additional daily medications for medical conditions other than their malignancy) and HV, the equation n!/(nr)!r! was utilized [38]
(where n is the total number of conventional medications
and HV being used and r was arbitrarily set at a value of
two). This equation uses permutations to calculate the
number of potential combinations allowed between a
number of items (i.e., conventional medications and HV).
459
Discussion
The results of this survey show that: (1) concurrent HV
use in patients receiving chemotherapy was frequent; (2) a
considerable percentage (28%, Table 5) of patients were
at risk of a detrimental chemotherapyHV interaction
according to the meta-analysis by Weiger et al. [37],
although additional data are needed to ascertain the
specific risk of interactions; (3) most patients would
discontinue their HV or ask their medical oncologists for
advice if a detrimental chemotherapyHV interaction was
possible; (4) although most patients reported discussing
460
their HV use with their oncologist, HV use was infrequently documented in medical records and most patients
also relied on their friends and naturopathic physician for
information regarding HV.
The overall use of CAM in this population was 76%,
which is similar to the proportions previously reported in
larger cohorts of adult cancer patients [5, 23, 30]. The
demographic characteristics of this population were such
that the patients would be expected to have a high use of
CAM. Over half (56%) of the participants were women
with breast cancer, who tend to use CAM more frequently
than those with other malignancies [23, 39]. In addition,
the participants were younger and predominantly women,
both of which are associated with CAM use [6, 30, 31].
Herbals/vitamins were amongst the most commonly
used CAM, as has been found in other studies [3, 12, 30,
34, 39]; notably, some cohorts in which HV use is
common include cancer survivors who have completed
treatment and thus would not be at risk for chemotherapyHV interactions [3, 12, 30]. The majority (78%) of
our study participants reported using HV, with the most
commonly used HV being multivitamins, calcium, and
vitamin C (Table 5). Ganz et al. reported that, in a
population of 763 long-term, disease-free female breast
cancer survivors, Echinacea, gingko, and garlic are the
most frequently used herbals [12]. Green tea, Echinacea,
shark cartilage, grape seed extract and milk thistle were
the most common herbals in a cross-sectional study of
100 adult cancer patients, with multivitamin, vitamin C
and vitamin E being the most popular vitamins [3]. Most
of our study participants reported daily use of HV,
suggesting a high likelihood of an interaction.
Several approaches have been taken to evaluate the
frequency of detrimental chemotherapyHV interactions.
Weiger et al. recently summarized the current evidence of
the efficacy and safety of selected CAM therapies with
the aim of developing evidence-based, patient-centered
advice on CAM use for these patients [37]. Based upon
their review, it would be reasonable to discourage the use
of three HV, specifically daily vitamin C, vitamin A and
soy, as summarized in Table 2. Three of our patients
reported using vitamin A, 14 were using vitamin C daily
and four were using HV with hormonal effects (i.e., black
cohosh, ginseng, dong quai). We also evaluated the use of
HV with antioxidant effects (used by 26 patients) and
with potential bleeding effects (used by 6 patients).
A pharmacokinetic interaction between chemotherapy
and St. Johns wort or garlic could have occurred in 3 of
the 56 participants receiving chemotherapy metabolized
by cytochrome P450 (e.g., cyclophosphamide, vincristine,
vinblastine, vinorelbine, and paclitaxel) [19, 27]. Recent
data in healthy volunteers suggest that St. Johns wort
and garlic increase the clearance of indinavir [26] and
saquinavir [27], respectively, both of which are cytochrome P450 3A4 (CYP3A4) and p-glycoprotein substrates. Also, St. Johns wort influences the metabolism of
461
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