Running Head: GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 1

Reducing Nausea and Vomiting in Chemotherapy Patients

Kellie Walker
NURS 612.01
5/06/14


























GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 2
Title
In patients receiving chemotherapy that are experiencing nausea and vomiting is the use
of ginger as effective as pharmacological measures in reducing these symptoms?
P Patients receiving chemotherapy that experience nausea and vomiting
I Use of ginger
C Pharmacological measures
O Reducing symptoms of nausea and vomiting
Background
Cancer, a disease caused by an abnormal and uncontrolled division of cells,
proves to remain as one of the leading causes of death worldwide despite the incremental
medical advances in society today. Cancer may be treated with surgery, radiation, and
chemotherapy. Nausea and vomiting are among the most prevalent side effects of
chemotherapy that may impact a persons quality of life significantly. Chemotherapy
induced nausea and vomiting (CINV) is normally treated through pharmacological
measures, which controls these adverse effects to a differentiating extent per individual.
CINV is classified into 3 types: acute CINV, which occurs during the first 24 hours post
chemotherapy; delayed CINV, which begins after 24 hors post chemotherapy and may
last for up to 6 or 7 days; and finally anticipatory CINV, which affects people who have
experienced severe nausea and vomiting in their previous administrations of
chemotherapeutic agents (Panahi, 2012, 2). Although significant advances have been
made in developing efficient anti-emetics, there are still many gaps in the control of these
symptoms. There are also many issues associated with patients refraining from taking
their chemotherapy medications due to the unpleasant side effects that aside from nausea
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 3
vomiting also include fatigue, pain, diarrhea, constipation, hair loss, mental status
changes, and more. As a result of the discontinuation from their curative medication
regimen, patients consequently hamper their chances of survival from cancer.
Alternative therapies that are non-pharmacological have been discussed to
concurrently reduce CINV alongside pharmacological methods. The conventionally
used anti-emetics, although effective in the acute phase, are ineffective in preventing the
delayed and anticipatory chemotherapy-induced nausea and vomiting (CINV) (Haniadka
et al, 2012, 1). It has been looked at as to what extent other measures may help in the
longer-term realm of therapy in relation to nausea and vomiting. Ginger, scientifically
known as Zingiber officinale Rosce, is a household medicinal agent and is widely used
for dyspepsia, flatulence, abdominal discomfort, and nausea. It has been recommended
for use as a carminative, diaphoretic, antispasmodic, expectorant, peripheral circulatory
stimulant, astringent, appetite stimulant, anti-inflammatory agent, diuretic, and a
digestive aid (Haniadka et al, 2012, 1-2). Ginger has also been incorporated specifically
into CINV; however, studies are fairly limited in quantity as to how effective ginger may
be for this cause. Research has ranged from animal studies, clinical studies, and
mechanistic studies in determining the effectiveness of ginger therapy. In all studies
ginger proved to provide reduced nausea and vomiting to some extent, but perhaps not as
accurately as pharmacological therapies, such as ondansetron, have done.
Rationale
This topic was chosen due to personal curiosity, class discussions, and available
evidence. Having a personal interest in oncology nursing drove me to pick this topic; I
work with hospice over the summers and breaks from college so I have naturally
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 4
developed attentiveness for cancer since many patients on hospice care concurrently have
cancer. During my work I do not witness chemotherapy because whilst in hospice
patients are no longer receiving life-enhancing treatments and have less than six months
to live. Therefore, I have a drive to learn more about what some people going through
before deciding to receive hospice care, and chemotherapy is definitely one of these
things. Chemotherapy induced nausea and vomiting is something that I feel should be
more of a focus. This is mostly due to the fact that evidence suggests patients are likely to
discontinue their treatment in relation to undesirable side effects such as nausea and
vomiting. Furthermore, I decided to look into measures beyond medication therapy in
order to help with this occurrence and ginger seemed to be one of the more prevalent
ways to do so.
Search Methods
To begin research on this topic I first accessed the UNH library website in which I
selected to look through databases to obtain my information. Medline was chosen and
through Ebsco Host I searched the terms nausea and ginger and also checked off the
option for linked full text as well as English language. This provided me with 34 articles
to sift through. I also typed in ginger and chemotherapy as key words with the same
restrictions of English language and linked full text. This yielded 16 results. Between
these two searches I was able to obtain four sufficient articles that provided me with
plentiful information to write this paper. One of my research articles provided a review of
other research studies conducted on the topic of choice. I chose the articles carefully
based on variability, evidence, and what was easiest for me to understand so I could
efficiently talk about ginger as it related to CINV.
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 5
Critical Appraisal of Evidence
The first article analyzed regarding ginger as a management for CINV was titled
Zingiber officinale (Ginger) as an Anti-Emetic in Cancer Chemotherapy: A Review.
This was a review where five previously performed studies were analyzed and looked
upon as a whole to validate the use of ginger as an antiemetic agent. The first research
looked at in this review was by Pace who reported that ginger was effective in reducing
CINV in patients with leukemia. The patients were randomized to receive oral ginger or
placebo in addition to prochlorperazine. There was a vast decrease in nausea and
vomiting for the group receiving ginger, not the placebo (Haniadka, 2012, 3). Next,
Manusirivithayas study was discussed; it was a randomized, double-blinded crossover
study of patients with gynecologic cancer receiving cisplatin-based chemotherapy. The
participants were divided into two groups; The first group received capsules of ginger
root powder orally 1g/day for 5 days, starting on the first day of chemotherapy, and in the
second group a placebo was given on the first day and metoclopramide was given orally
for 4 days after. Afterwards, the patients were crossed over and received the opposite
therapy in their second cycle of chemotherapy. This study reveled that there wasnt a
significant difference in the reduction of nausea and vomiting between the two different
therapies. The present study showed that addition of ginger to a standard anti-emetic
regimen has no advantage in reducing nausea or vomiting in acute phase of cisplatin-
induced emesis and also that in the delayed phase, ginger and metoclopramide have no
difference in their efficacy (Haniadka, 2012, 3). The next study that this review analyzed
was crossover and double blind. Sontakke et al administered patients 1000 mg of ginger
twenty minutes before receiving chemotherapy and six hours afterwards. Patients were
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 6
assigned to either receive ginger or metoclopramide or ondansetron during the first cycle
and then were crossed over to the opposing regimen in the next two cycles. At the end of
the study, the investigators observed complete control of nausea in 62% of patients on
ginger, 58% with metoclopramide, and 86% with ondansetron. Complete control of
vomiting was achieved in 68% of patients on ginger, 64% with metoclopramide, and 86%
with ondansetron. Ginger was observed to be devoid of any adverse effects, suggesting
that it is safe and effective (Haniadka, 2012, 3). Concurrent observations were seen by
Levine et al who also observed that adding a protein-rich diet in combination with ginger
decreased delayed nausea from chemotherapy. This review included one study that
contradicted these observations. Zick et al performed a randomized, double blind,
placebo controlled trial in which patients were to receive either one-gram of ginger, 2
grams of ginger, or a placebo. In the end, ginger provided no reduction in CINV in a
delayed or an acute sense. Overall, these reports indicate that ginger is a promising anti-
emetic herbal remedy. However, the clinical data are insufficient to draw firm
conclusions. Due to its abundance, low cost, and safety in consumption, ginger remains
a species with tremendous potential and countless possibilities for further investigation.
Ginger has the potential to develop as a nontoxic anti-emetic agent against chemotherapy
and radiation-induced nausea, when gaps existing in knowledge are bridged (Haniadka,
2012, 4). This review of studies was effective by incorporating and summarizing what
has been previously reported and found and taking it into account as a whole. A negative
aspect noted from this outline was that the results varied worldwide, from many
countered, in which many factors may be different. There wasnt enough information
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 7
provided about where the other studies came from in order to detect if accuracy was
viable.
The second research that was viewed on this topic was titled Effect of Ginger on
Acute and Delayed Chemotherapy-Induced Nausea and Vomiting: A Pilot, Randomized,
Open-Label Clinical Trial by Panahi et al. This was aimed at patients who had the
diagnosis of breast cancer and it evaluated the effects of ginger against both acute and
delayed CINV. These women were initially assigned to a standard chemotherapy protocol
of docetaxel, epirubicin, and cyclophosphamide. A number were additionally selected to
receive ginger at a dose of 1.5 grams in three divided doses every eight hours as well as
antiemetic agents (granisetron and dexamethasone). The control groups did not receive
ginger concurrently. Prevalence, score and severity of nausea, vomiting, and retching
were assessed using a simplified form of Rhodes index in the first 6 hours, between 6 to
24 hours, and days 2, 3, and 4 post chemotherapy. Addition of ginger (1.5g/d) to
standard antiemetic therapy (granisetron plus dexamethasone) in patients with advanced
breast cancer effectively reduces the prevalence of nausea 6 to 24 hours post
chemotherapy. However, there is no other additional advantage for ginger in reducing
prevalence or severity of acute or delayed CINV (Panahi et al, 2012, 2). This study was
effective in obtaining significant evidence on a specific type of cancer in regards to
ginger therapy for nausea and vomiting. Limitations included a lack of blindness because
ginger possesses a unique and predictable aroma. There were overall negative findings on
ginger being more effective than medication regimens; it is slightly unclear if this was
due to problems with the blindness of the study or if there really is not a meaningful
variance. Further larger scale double-blind trials are recommended to verify the results
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 8
of the current pilot trial. Prospective studies and longer periods of follow-up are also
helpful to assess the efficacy of ginger supplementation on the prevalence of CINV
symptoms in patients receiving multiple cycles of chemotherapy (Panahi et al, 2012, 8).
In correlation with the previous research review of studies analyzed, this one also noted
more research is needed to confirm or deny ginger as a more effective measure than
medication therapy.
The third article reviewed the management of CINV as a whole on newer agents
and newer uses for older agents. Antiemetic agents defined in this study by Navari are
dopamine receptor antagonists, serotonin 5Hts receptor antagonists, dopamine-serotonin
receptor antagonists, neurokinin, dexamethasone, olanzapine, gabapentin, cannabinoids,
and ginger. In specificity to ginger the study states ginger is an herbal supplement that
has been used for reducing the severity of motion sickness, pregnancy-induced nausea
and PONV. The mechanism of action by which ginger might exert antiemetic effects is
unclear. Human experiments to determine the mechanism, of action show varying
results regarding gastric motility and corpus motor response (Navari, 2013, 10). This
study, like the others notes that there are not enough available evidence to support or
deny ginger as an agent to prevent CINV. It concluded by addressing each of the above
stated agents and how effective they may be for CINV. Ginger specifically was not noted
to have enough evidence to support this, suggesting combination therapy with other
agents to reduce both acute and delayed incidence of chemotherapy induced nausea and
vomiting. This study could have been greatly improved by comparing and contrasting the
differences between the various agents they discussed that are available to reduce nausea
and vomiting. Their research showed whether they are all shown to work effectively for
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 9
these adverse effects, but it doesnt take into account what ones are better and in which
stage of CINV.
Weimer et al was the author of the final research study analyzed for the purposes
of this paper and it was titled Effects of Ginger and Expectations on Symptoms of
Nausea in a Balanced Placebo Design. Sixty-four healthy participants were selected and
randomly assigned to receive either anti-emetic ginger or a placebo. They all were
exposed to sequences to induce nausea such as rotations, cortisol, and electrogastrograms.
The rotations consisted of being blindfolded and being spun in a standardized fashion
five separate times for duration of two minutes which a one-minute interruption between
each. They were to rotate 120 degrees per second and were instructed to move their heads
up or down every ten seconds. At the end they rated their symptoms in relation to vertigo,
headache, nausea, urge to vomit, fatigue, sweating, and stomach awareness. In addition,
the cortisol was done at the beginning of the experiment, immediately before rotation,
after rotation termination and 15 min following rotation termination in which saliva
samples were taken and analyzed for the presence. Finally, the electrogastogram (EGG)
monitored gastric activity; three electrodes were placed on the participants stomachs and
abnormal myoelectrical activity was noted (Weimer, 2012, 2-3). The results of this
experiment were negative in the fact that ginger did not effectively have an anti-emetic
effect. This study was conducted in an interesting and efficient way. However, the
downsides include that different participants may have had different past medical
histories possibly already including motion sickness or related areas. Also, the missing
effect of ginger may be explained by the higher intensity of stimulation that [they] used
in this study and that they may have been to strong to be overcome by a weak
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 10
antiemetic (Weimer, 2012, 5). These patients were also healthy, not receiving
chemotherapy; however, it still can correlate to the research required for this paper in the
sense that ginger was specifically used to attempt to reduce nausea and vomiting as well
as other side effects.
Evidence Synthesis
After analyzing and reviewing the previously stated research conclusions can be
drawn stating ginger is effective in reducing chemotherapy induced nausea and vomiting.
However, it is unclear as to whether ginger works as a better anti-emetic than
pharmacological measures as it relates to chemotherapy. Three of the four sources found
ginger being overall fairly effective in reducing CINV, however, they find it to be similar
in effect to medications such as ondansetron and metoclopramide. There is no evidence
suggesting ginger is more effective than these pharmacological measures, but there is
also minimal evidence suggesting it is any worse. The research found was minimal and
limited and more definitely needs to be done in order to accurately determine whether
ginger can be properly and efficiently used as alternative anti-emetic therapy rather than
medical means. Basically, it is in CINV regimens to provide antiemetic agents in the
form of medications, but ginger is slowly approaching as a measure to do the same. There
is no significant evidence currently to add ginger into the regimen for CINV, but it is
coming forward.
Clinical and Research Recommendations
Based on my critical appraisal of the evidence as well as the evidence synthesis
recommendations can be put forth. For nurses in particular, ginger research as it relates to
CINV may become more prevalent in the clinical setting. Therefore, patients will become
GINGER AS AN ANTIEMETIC IN CHEMOTHERAPY PATIENTS 11
more aware of this therapy and it may become the nurses role to help a patient decide if
they would like to try ginger supplementation. I would personally classify ginger
treatment as simply an idea thus far; there is not enough extensive research to fully grasp
if this means of therapy will succeed. There needs to be much more depth in research
studies before ginger can be classified as effective a measure as pharmacological
methods. In the limited studies I found regarding ginger as it relates to CINV it was
found that it does in fact reduce nausea and vomiting, however, there needs to be more
significant research done in order to confirm this with more validity. From what I have
seen from the studies found, it seems ginger research needs to be more developed in areas
such as correlating side/adverse effects, dosing, what route of administration works best,
and so forth. I feel that if this is looked at more seriously, in depth, and with an
accumulation of more studies it can prove to be effective in treatment.











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References
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Alternative And Complementary Medicine (New York, N.Y.), 18(5), 440-444.
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Navari, R. (2013). Management of chemotherapy-induced nausea and vomiting : focus on
newer agents and new uses for older agents. Drugs, 73(3), 249-262.
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(2012). Effect of ginger on acute and delayed chemotherapy-induced nausea and
vomiting: a pilot, randomized, open-label clinical trial. Integrative Cancer
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balanced placebo design. Plos One, 7(11), e49031.
doi:10.1371/journal.pone.0049031
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