Complementary Therapies in Medicine 56 (2021) 102587

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Complementary Therapies in Medicine

journal homepage: www.elsevier.com/locate/ctim

The Effects of Peppermint Oil on Nausea, Vomiting and Retching in Cancer

Patients Undergoing Chemotherapy: An Open Label Quasi–Randomized
Controlled Pilot Study
Nuriye Efe Ertürk a, *, Sultan Taşcı b
a
Department of Nursing, Batman University Health College, Batman, Turkey
b
Department of Internal Medicine Nursing, Erciyes University Faculty of Health Science, Kayseri, Turkey

A R T I C L E I N F O A B S T R A C T

Keywords: Objectives: The current study evaluated the effects of peppermint oil on the frequency of nausea, vomiting,
Aromatherapy retching, and the severity of nausea in cancer patients undergoing chemotherapy.
Chemotherapy Design: A quasi-randomized controlled study.
nursing
Setting: Patients were recruited from the ambulatory chemotherapy unit of a public hospital located (Batman,
Nausea-Vomiting
Peppermint
Turkey) between September 2017 and September 2018.
Interventions: The participants in the intervention group applied one drop the aromatic mixture on the spot
between their upper lip and their nose, three times a day for the five days following chemotherapy adminis­
tration, in addition to the routine antiemetic treatment. Participants in the control group underwent only the
routine antiemetic treatment. Main outcome measures VAS-the severity of nausea and the Index of Nausea,
Vomiting, and Retching.
Results: The VAS nausea score was significantly lower after peppermint oil applying in the patients receiving
Folfirinox (treatment effect (mean dif.): 4.00±2.28; P<0.001), Paclitaxel-Trastuzumab (treatment effect (mean
dif.): 1.70±0.90; P=0.014), Carboplatin-Paclitaxel (treatment effect (mean dif.): 3.71±1.41; P<0.001), and
Cyclophosphamide-Adriamycin (treatment effect (mean dif.): 1.41±0.73; P=0.005) excluding cisplatin scedule
(treatment effect (mean dif.): 0.56±2,18; P=0.642). We detected a statistical significant difference in the change
in frequency of nausea, vomiting, retching in the other all schedules excluding cisplatin schedule (P<0.05).
Conclusions: The peppermint oil was significantly reduced the frequency of nausea, vomiting, retching and the
severity of nausea in cancer patients undergoing chemotherapy. Therefore, usage of peppermint oil together with
antiemetics after chemotherapy with moderate and low emetic risk may be recommended to cope with CINV.

1. Introduction
Nausea, vomiting and retching are among the most common adverse
effects of chemotherapy and are defined by some patients as their
biggest problem worse than the pain.1–5 Chemotherapy-induced nausea
and vomiting (CINV) are reported to lead to fluid-electrolyte imbalance,
dehydration, weight loss, physiological effects caused by poor drug
absorption and/or decreased elimination from kidneys. They also have
negative effects on the patients’ social life, work life, daily activities and
psychological well-being. Besides, nausea and vomiting cause some
patients to refuse chemotherapy or to discontinue the treatment.6–10
The chemotherapy agents have different emetogenic potential as
minimal, low, moderate and high.1,2,11 Therefore, the patients experi­
ence different levels of CINV according to their chemotherapy regimens.
Although CINV is experienced in different frequencies, in recent studies,
it has been reported that nausea and vomiting are experienced over 70%
and 50%, respectively.12,13,14 In the medical management of CINV, an­
tiemetics are recommended according to the emetogenic potentials of
the chemotherapy agents.2,11,15,16 Although nausea and vomiting, in
particular, have been successfully managed, with 5- hydroxytryptamine
3 (5-HT3) receptor antagonists, corticosteroids, and neurokinin 1 (NK-1)
receptor antagonists, they have not yet been completely controlled
yet.3,14,17,18In addition, these drugs are reported to have such adverse
effects as heartburn, insomnia, headache, dizziness,

* Corresponding author at: Department of Nursing, Batman University Health College, Batman, Turkey
E-mail address: nuriye_efe@hotmail.com (N. Efe Ertürk).

https://doi.org/10.1016/j.ctim.2020.102587
Received 27 March 2020; Received in revised form 29 August 2020; Accepted 28 September 2020
Available online 9 October 2020
0965-2299/© 2020 Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
N. Efe Ertürk and S. Taşcı
constipation/diarrhea, akathisia, ataxia, pharyngeal itching, and dry
mouth.6,19–21 Inadequate control of CINV leads patients to integrative
health practices.10,22,23 The complementary and integrative health
practices that are frequently used by patients include acupuncture,
acupressure, imagery/dreams, psycho-educational support, exercise,
hypnosis, massage, and aromatherapy.7,10,22–26
Aromatherapy is the use of essential oils produced from pleasant-
smelling parts of plants, to treat or relieve physical and emotional
symptoms.27 There are a limited number of studies in the relevant
literature about the use of essential oils to cope with CINV.8,28–33
Therefore, aromatherapy is among the integrative applications for
coping with CINV whose efficacy has not yet been established.24,25 One
of the essential oils used in studies investigating the effect of aroma­
therapy on CINV is peppermint essential oil. The peppermint essential
oil is known to be effective in nausea.34,35 However, there are a few
study on its effects in CINV. The study which conducted by Zorba and
Özdemir31 demonstrated that massage and inhalation of aromatic
mixture including peppermint oil significantly reduced CINV. Similarly,
in other studies which are performed by using peppermint essential oil, a
decrease in severity of nausea and frequency of vomiting was
determined.30–33 This study is aimed to help the patients who suffering
from CINV and contribute to the planning of evidence-based in­
terventions on the effects of aromatherapy in the management of CINV.
2. Hypotheses of the study
H11. The peppermint oil applied on the spot between their upper lip
and their nose (on their philtrum) of patients, one drop three times a day
during the five days following chemotherapy administration is effective
on reducing the incidence of CINV in cancer patients.
H12. The peppermint oil applied on the spot between their upper lip
Fig. 1. CONSORT flow diagram.
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Complementary Therapies in Medicine 56 (2021) 102587
and their nose (on their philtrum) of patients, one drop three times a day
during the five days following chemotherapy administration is effective
on reducing the severity of nausea in cancer patients.
3. Materials and methods
3.1. Study design and sample size
This study was conducted in the ambulatory chemotherapy unit of a
public hospital located in a city in Turkey. This study was undertaken in
two phases: the quantitative and the qualitative phases. The quantitative
phase of the study was realized as a quasi-randomized controlled study
exploring the effects on the incidence of nausea, vomiting, retching and
the severity of nausea of the peppermint oil after chemotherapy. Before
starting the study, the aromatic mixture was administered to five pa­
tients to determine whether of the oils has side effect or not. After this
practice it was observed that peppermint oil has no side effects. These
patients were not included to sample size of the study. No placebo
intervention was applied due to characteristic odor of peppermint oil.
Therefore, blinding of researchers and patients to study groups could not
be achieved. The qualitative phase of the study was realized using semi-
structured question forms and individual in-depth interviews with the
patients of the intervention group before they had chemotherapy and at
the end of follow-up.
From September 2017 to September 2018, a total of 250 of cancer
patients undergoing chemotherapy administiration were screened, of
whom 140 met all inclusion criteria. Of these 140 patients, 50 refused to
partipate, 90 patients agreed to participate in the study. Finally, a total
of 80 completed the study: 36 patients from in the intervention group
and 44 patients from in the control group. Fig. 1 depicts reasons for dis-
continuing the participation of the participants (See Fig. 1). The inclu­
sion criteria for participant selection were as follows: (a) adults aged
N. Efe Ertürk and S. Taşcı Complementary Therapies in Medicine 56 (2021) 102587

≥18 years who were able to understand and communicate in the Turkish
language, (b) were diagnosed with cancer, (c) were experienced nausea
of any severity, (d) had at least two remaining chemotherapy treatment
using similar chemotherapeutic agents; (e) were not pregnant (f) had at
most stage III cancer, (g) presented no psychiatric disorders and approve
to participate in the study. Exclusion criteria of the study: (a) had allergy
to peppermint or carrier oil, (b) had any record of respiratory diseases
like asthma and chronic obstructive pulmonary diseases, (c) had record
of with diseases leading to vomiting such as hepatic and renal failure
28,29,31
In this study, the participants in the intervention and control
groups were compared according to the chemotherapy treatment pro­
tocols due to the chemotherapy agents have different emetogenic
potentials.
3.2. A quasi-randomization allocation method
In this study, the participants were assigned to groups using “an
alternating quasi-randomization allocation method”.36 The ballot
method was used to determine which group would start the study. After
balloting, the first patient visiting the daytime the ambulatory chemo­
therapy unit was allocated to the intervention group, while the second
patient was control group, respectively. The process continued until the
desired sample size was reached.
3.3. Outcome measurement tools
The data were collected using a patient information form, a Visual
Analog Scale (VAS) for nausea severity, patient watch chart, the Index of
Nausea, Vomiting, and Retching (INVR), The Aromatherapy Practice
Guide, patient opinions form on aromatherapy practice.
3.3.1. Patient Information Form
The patient information form is consisted of 9 statements exploring
the patients’ sociodemographic characteristics (age, sex, educational
status), diagnosis, treatment protocol, and complementary and inte­
grative health practices used to cope with cancer and with the symptoms
of nausea and vomiting.28,29,31
3.3.2. Visual Analog Scale for Nausea Severity
A Visual Analog Scale for Nausea Severity was used to choose pa­
tients for the study and to determine the efficacy of treatment. The VAS
is composed of a 10-cm line on the left of which is “No nausea 0.” The
numbers increase to the right, indicating rising nausea levels; at the right
end is “Severe nausea 10.” The patient is asked to place a mark on the
scale to indicate the level of intensity of his or her nausea.28,29,31,33
distress caused. There are three subdimensions: symptoms experience,
symptoms occurrence, and symptoms distress. To score the INVR the 1st,
3rd, 6th, and 7th items are reversed. Turkish validity and reliability tests
of the index were performed by Genç and Tan26; the internal consistency
was found to be 0.95 and the alpha internal consistency of sub­
dimensions ranged from 0.81 to 0.95. In the current study the Cron­
bach’s alpha of the index was found to be 0.94 in the intervention group
after aromatherapy and 0.96 in the control group.
3.3.5. The Aromatherapy Practice Guide
The Aromatherapy Practice Guide was prepared in line with expert
opinion and literature to show the stages and important points of
applying an essential oil and to make sure that the oil would be applied
in the same manner by all the patients (See Fig. 2).37,39
3.3.6. Patient Opinions Form on Aromatherapy Practice
The patient opinions form on aromatherapy practice included sem­
istructured questions designed in line with expert opinions and litera­
ture to identify the opinions of the patients in the intervention group
about the aromatherapy.37 The patients were asked questions in the
form before and after aromatherapy, and the patients’ opinions were
voice-recorded or written down.
3.4. Interventions
All patients in the intervention and control groups were prescribed
intravenous granisetron (3 mg), dexamethasone (16 mg) and metoclo­
pramide HCL (10 mg) before chemotherapy. After chemotherapy,
medications home treatment for CINV were prescribed antiemetic pro­
phylaxis containing oral ondansetron (8 mg) and oral metoclopramide
(10 mg) by the oncologist.
3.4.1. The control group
The control group did not receive any treatments, only were
instructed to use their antiemetic medications as suggested by the
oncologist. Patients in the control group filled out the patient nausea
severity follow-up and INVR forms and returned them to the researcher
when they came to the hospital for their next chemotherapy treatment.
The INVR form of patients who were illiterate were filled in by the
pollster according to responses from the patient so that the researcher
did not interfere. To fill in the INVR scale phone interviews were done

3.3.3. Patient Watch Chart

The patient watch chart for the intervention group was designed
after a thorough review of the relevant literature.29,37 This form was
prepared to record patients’ application status of peppermint oil (for 5
days) and problems that may occur during the application process. Pa­
tients in the intervention group filled out this form and delivered it to the
researcher when they came to the hospital for their next chemotherapy
treatment.

3.3.4. The Index of Nausea, Vomiting, and Retching

The Index of Nausea, Vomiting, and Retching (INRV) was developed
by V. Rhodes and R. Mc Daniel 38 in order to explore the frequency of
patients’ post-chemotherapy nausea, vomiting, retching, and the
distress they experience from these symptoms. The index is composed of
eight questions. The index assigns a numeric value from 0 (the least
amount of distress) to 4 (the most distress) to each response. The pa­
tient’s total experience of nausea and vomiting is calculated by summing
the patient’s responses to the eight items on the INVR. The potential
range of scores is from a low of 0 to a maximum of 32. Patients rate their
symptoms over the preceding 12 hours for occurrence, frequency, and Fig. 2. The Aromatherapy Practise Guide.

3
N. Efe Ertürk and S. Taşcı
twice a day (morning and evening) by each pollster and participant at a
time suitable for both.
3.4.2. Intervention group
The participants in the intervention group applied one drop the ar­
omatic mixture on the spot between their upper lip and their nose (on
their philtrum), three times a day for the five days following chemo­
therapy administration, in addition to the routine antiemetic treatment.
They were asked to take deep breaths after applying the aromatic
mixture. The researcher provided 8-10 minutes of theoretical and
practical training about the use of aromatic mixture beforehand. The
patients were requested to apply this mixture three times a day for five
days according to “The Aromatherapy Practice Guide” (See Fig. 2): in the
morning (9:00 a.m.), in the afternoon (3:00 p.m.) and in the evening
(9:00 p.m.). The mobile phones of the participants were set to these
times, and this alarm system was used for five days. The participants
whose mobile phones could not set to these hours were called by the
researcher to remind them for application. The participants were asked
the questions on the patient opinions form before and after they applied
the aromatic mixture, and their answers were recorded. The patient
watch charts, VAS for nausea severity, and the INVR scales were filled in
by the patients and returned to the researcher when the patients came to
the hospital for their next chemotherapy treatment. The patient watch
charts and INVR scales of patients who were illiterate were filled in by
the pollster according to responses from the patient. In order to fill in the
patient watch charts and INVRs, phone interviews were done twice a day
(morning and evening) by the pollster and the participants.
3.5. Aromatic mixture
It is recommended to dilute aromatic oils to 2.5-3% in constant oils
so that they can be applied safely to the skin of adults.40,41 In addition to
this, expert opinion was consulted on preparing the mixture. Therefore,
the aromatic mixture was prepared at a rate of 3% and to use sweet
almond oil as the base oil. The aromatic oils were supplied from essential
oils produced by the Nu-Ka Defne Esencia Company in Alanya/Turkey.
The aromatic mixture (30 mL) was stored in dark- colored glass bottles.
The patients were told to keep the aromatic mixture closed in a light-free
environment.
3.6. Data analysis
For the assessment of the study, IBM SPSS Statistics for Windows,
version 23.0 (California). Chi-square and Fisher’s exact tests were used
to evaluate the differences in terms of descriptive variables. The distri­
bution of numerical values was analyzed with the Shapiro–Wilk
normality test, and the homogeneity of variances was analyzed using
Levene’s test. The Mann–Whitney U-test, the independent-samples t-
test, and paired sample t-test were used to compare the two groups. P <
0.05 values were considered to be statistically significant.
In this study, to determine the sample size while patients were being
allocated to the study groups, post hoc power analysis was periodically
done with the data obtained. The sample size was calculated with post-
hoc manner by using the G Power Software (version 3.1.7). The power of
study power was determined as 99.9% by calculating the difference
between the VAS scores averages according to power analysis α = 0.05
and d = 1.68.
The qualitative data were evaluated in six phases of thematic anal­
ysis. The six phases consisted of familiarization with the data, coding,
searching for themes, reviewing themes, defining and naming themes,
and writing them up.42 In this process, firstly the full contents of the
records were transcribed and then the data were read repeatedly. The
content analysis of the interviews was conducted by two separate re­
searchers. The contents were categorized by most appropriate category
and subcategory.
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Complementary Therapies in Medicine 56 (2021) 102587
3.7. Ethical considerations
The study conformed to the principles of the Declaration of Helsinki.
Participants gave their written informed consent to take part in the
study, ethical approval (decision numbered: 2017/72) was obtained
from the Clinical Research Ethics Committee of Erciyes University in
Turkey, and written permissions were obtained from the institution
where the study was done (decision numbered: 16.02.2017-75144452).
4. Results
4.1. Quantitative Findings
While 67.7% of the patients in intervention group were women, the
68.2% of patients in control group were women. The illiterate percent of
patients was 44.5 in intervention group and 40.9 in control group,
respectively. The average age of the patients in the intervention group
was 49.94 ± 10.47 and 54.63 ± 10.15 in the control group. In terms of
descriptive and disease characteristics, the participants in the inter­
vention and control groups were similar (P > 0.05; Table 1).
The participants in the intervention and control groups had similar
median scores by chemotherapy treatment protocol at the baseline
measurements (P > 0.05) (Table 2). After peppermint oil practice, last
follow-up score of the VAS nausea score significantly decreased ac­
cording to the baseline score in the patients receiving folfirinox (treat­
ment effect (mean dif.): 4.00 ± 2.28; P < 0.001), paclitaxel-trastuzumab
(treatment effect (mean dif.): 1.70±0.90; P = 0.014), carboplatin-
paclitaxel (treatment effect (mean dif.): 3.71±1.41; P < 0.001), and
cyclophosphamide-Adriamycin (treatment effect (mean dif.):
1.41±0.73; P = 0.005) excluding cisplatin schedule (treatment effect
(mean dif.): 0.56±2,18; P = 0.642). This difference was no significant in
the control group. However, during the other follow-ups days (till Day-
5), The VAS nausea severity scores of the patients in the intervention
group were lower than those of the patients in the control group
receiving the folfirinox, paclitaxel-trastuzumab, carboplatin-paclitaxel
(excluding on the evening after chemotherapy), and cyclophosphamide-
adriamycin treatment protocols (except the evening after chemotherapy
and the first day after it) (Table 3).
The distribution of the INVR scale total average score by follow-up
day and chemotherapy treatment protocol of the participants in the
intervention and control groups is presented in Table 4. The INVR daily
average scores of the patients who received folfirinox (1st day P < 0.001;
2nd day P = 0.007; 3rd day P < 0.001;4th day P < 0.001), paclitaxel-
trastuzumab (1st day P = 0.223; 2nd day P = 0.047; 3rd day P =
0.021;4th day P = 0.022), carboplatin-paclitaxel (1st day P = 0.041; 2nd
day P = 0.013; 3rd day P = 0.010;4th day P = 0.003) and
cyclophosphamide-adriamycin chemotherapy treatment (1st day P =
0.007; 2nd day P = 0.015; 3rd day P = 0.036;4th day P = 0.041) were
lower than those of the participants in the control group (excluding the
1st day of patients receiving paclitaxel-trastuzumab), and the difference
between the groups was significant on all follow-up days (p < 0.05). The
daily average INRV scores of the patients who received cisplatin 1st day
P = 0.784; 2nd day P = 0.156; 3rd day P = 0.229;4th day P = 0.407 were
not lower than those of the participants in the control group.
4.2. Qualitative Findings
The qualitative findings were presented in the Table 5. The quali­
tative data was evaluated under three heading as the main category,
subcategory, and example of data.
5. Discussion
According to the follow-ups in this study, the incidence of nausea,
vomiting, retching and feelings of distress caused by these symptoms
were significantly lower among patients in the intervention group
N. Efe Ertürk and S. Taşcı Complementary Therapies in Medicine 56 (2021) 102587

Table 1
Distribution of descriptive and disease characteristics of participants.
Characteristics Groups P

Intervention Control Group

Group (n = (n = 44)
36)

Female 24 67.7 30 68.2

Sex 0.886a
Male 12 33.3 14 31.4
Illiterate 16 44.5 18 40.9
Literate 7 19.4 13 29.5
Educational status 0.625a
Primary school-Middle School 8 22.2 6 13.7
High school and over 5 13.9 7 15.9
49.94 ±
Average age (M ± SD) 54.63 ± 10.15 0.335b
10.47
Breast cancer 13 36.1 16 45.6
Colon cancer 10 27.8 8 20.5
Ovary cancer 4 11.1 4 9.0
Disease diagnosis 0.962a
Lung cancer 4 11.1 5 11.4
Rectum cancer 3 8.3 3 9.0
Pancreas cancer 2 5.6 2 4.5
Folfirinox (Folinic acid, fluorouracil, irinotecan,
a 14 38.9 16 36.4
nd oxaliplatin)
Carboplatin AUC < 4 -Paclitaxel 7 19.4 9 20.5
Chemotherapy treatment protocol 0.928a
Cyclophosphamide –Adriamisin 6 16.7 5 11.3
Paclitaxel-Trastuzumab 5 13.9 9 20.5
Cisplatin 4 11.1 5 11.3
Status of using integrative health practices in previous chemotherapy Yes 2* 5.6 2** 4.5
0.837a
treatments No 34 64.4 42 95.5
Status of using non-medical treatment practices in previous chemotherapy Yes 2*** 5.6 4**** 9.1
0.360a
treatments in order to prevent nausea No 34 94.4 40 90.9
Yes 34 94.4 43 97.7
Status of receiving training on chemotherapy side effects 0.442a
No 2 5.6 1 2.3
Doctor/Medical oncologist 27 79.4 36 83.7
Professional provided training on chemotherapy side effects 0.626a
Nurse/Training nurse 7 20.6 8 16.3

M ± SD, mean plus/minus standard deviation

*
A herbal mixture brought from Iran, and a mixture of bee products.
**
Reishi mushroom, and a mixture of bee products.
***
Chickpea powder and lemon juice.
****
Ginger powder(2), chickpea powde, and black seed.
a
Obtained from the chi-square test.
b
Obtained from the independent-samples t-test.

Table 2
The difference between the nausea severity scores-VAS of the participants in the intervention and control groups according to measurements.
Chemotherapy treatment protocol (Schedule) Groups Measurements Treatment effects Pa Pb

Baseline* Last** Mean diff. (95%

CI)

Folfirinox (Folinic acid, fluorouracil, irinotecan, and oxaliplatin) Intervention Group (n = 14) 6.03 ± 1.30 2.03 ± 1.48 4.00 ± 2.28 <0.001
0.778
schedule Control Group (n = 16) 6.21 ± 2.07 6.84 ± 2.46 − 0.62 ± 1.53 0.124
Intervention Group (n = 5) 4.80 ± 0.67 3.10 ± 1.40 1.70 ± 0.90 0.014
Paclitaxel-Trastuzumab schedule 0.511
Control Group (n = 9) 4.33 ± 1.43 4.80 ± 1.13 − 0.47 ± 0.77 0.105
Intervention Group (n = 7) 6.71 ± 1.95 3.00 ± 1.11 3.71 ± 1.41 <0.001
Carboplatin AUC< 4-Paclitaxel schedule 0.386
Control Group (n = 9) 5.77 ± 2.16 5.61 ± 2.04 0.16 ± 1.41 0.733
Intervention Group (n = 6) 5.58 ± 0.97 4.16 ± 0.51 1.41 ± 0.73 0.005
Cyclophosphamid-Adriamycin schedule 0.259
Control Group (n = 5) 4.90 ± 0.89 5.00 ± 0.70 − 0.10 ± 0.54 0.704
Intervention Group (n = 4) 7.87 ± 2.49 7.31 ± 0.47 0.56 ± 2,18 0.642
Cisplatin schedule 0.219
Control Group (n = 5) 6.20 ± 1.15 7.20 ± 1.78 − 1.00 ± 1.69 0.258
*
Baseline: The severity of nausea, which experienced in the previous chemotherapy treatment.
**
The highest VAS score marked by patient during 5-day follow-up.
a
Paired t-test was done.
b
Independent t-test was done for compare to the baseline measurements of the participants.

receiving folfirinox, paclitaxel- trastuzumab (after the first day),
carboplatin-paclitaxel, and cyclophosphamide- adriamycin than in the
control group. In addition to this, last follow-up score of the VAS nausea
score significantly decreased according to the baseline score in the pa­
tients receiving folfirinox, paclitaxel-trastuzumab, carboplatin-pacli­
taxel, and Cyclophosphamide-Adriamycin. This difference was no
significant in the control group. However, during the other follow-ups
days, the VAS nausea severity scores of the patients in the interven­
tion group were lower than those of the patients in the control group in
the folfirinox, paclitaxel- trastuzumab, carboplatin- paclitaxel (except
on the evening after chemotherapy), and cyclophosphamide- adria­
mycin treatment protocols (except the evening after chemotherapy and

5
N. Efe Ertürk and S. Taşcı Complementary Therapies in Medicine 56 (2021) 102587

Table 3
Distribution of VAS- the severity of nausea average scores of the participants according to measurement time and chemotherapy treatment protocol.
Chemotherapy treatment protocol Groups VAS- the severity of nausea average
(Schedule) scores according to measurement
time
Evening of the chemotherapy day 1 st day median 2nd day median 3rd day median 4th day median
median (%25p- %75p) (%25p- %75p) (%25p- %75p) (%25p- %75p) (%25p- %75p)

Folfirinox (Folinic acid, fluorouracil, Intervention 0.00 (0.00-0.25) 0.00 (0.00- 1.25 (0.00- 0.50 (0.00- 0.75 (0.45-
irinotecan, and oxaliplatin) Group (n = 14) 1.12) 2.50) 2.50) 1.05)
schedule
Control Group (n 2.00 (0.37-2.87) 3.5 (2.62-4.43) 4.37 (3.31- 4.75 (3.37- 4.12 (3.00-
= 16) 5.37) 7.87) 4.84)
p* <0.001 < 0.001 < 0.001 < 0.001 < 0.001
es** 0.63 0.78 0.68 0.8 0.82
Paclitaxel-Trastuzumab schedule Intervention 0.00(0.00-1.00) 1.00 (0.00- 1.75 (0.00- 1.50 (1.12- 0.00 (0.00-
Group (n = 5) 1.50) 2.25) 2.62) 1.00)
Control Group (n 2.00 (1.00-2.75) 2.75 (1.75- 4.00 (3.50- 3.50 (3.00- 3.00 (1.25-
= 9) 3.00) 4.62) 5.12) 3.87)
p* 0.039 0.022 0.002 0.016 0.004
es** 0.55 0.61 0.8 0.64 0.77
Carboplatin AUC< 4-Paclitaxel Intervention 0.00 (0.00-1.00) 0.00 (0.00- 1.50 (0.00- 1.75 (0.00- 1.00 (0.62-
schedule Group (n = 7) 1.00) 3.30) 2.75) 1.12)
Control Group (n 2.00 (1.00-3.25) 4.00 (1.87- 4.00 (3.12- 5.75 (3.00- 4.12 (2.28-
= 9) 4.75) 6.62) 6.12) 5.25)
p* 0.059 0.005 0.007 0.005 0.002
es** 0.7 0.68 0.7 0.78
Cyclophosphamid-Adriamycin Intervention 0.00 (0.00- 2.12) 1.25 (0.00- 1.12 (0.75- 1.25 (0.75- 0.81 (0.67-
schedule Group (n = 6) 2.62) 2.43) 1.81) 1.92)
Control Group (n 3.00 (1.00-3.50) 3.00 (1.50- 4.74 (1.12- 4.75 (3.12- 3.68 (2.65-
= 5) 3.87) 5.50) 7.50) 5.50)
p* 0.068 0.132 0.027 0.006 0.004
es** 0.67 0.83 0.75
Cisplatin schedule Intervention 4.00 (1.62-5.62) 5.50 (3.25- 5.75 (3.62- 6.00 (4.50- 4.68 (4.06-
Group (n = 4) 7.18) 6.75) 6.75) 6.57)
Control Group (n 5.50 (3.25-7.18) 4.25 (3.62- 8.25 (6.00- 8.00 (6.00- 7.06 (4.68-
= 5) 7.00) 9.12) 8.00) 7.43)
p* 0.319 1 0.108 0.118 0.537

Bold values shows the significant difference, P < 0.05.

*
Mann-Whitney U test was done.
**
Effect size.

the first day after it). However, among the patients receiving cisplatin,
there was no significant difference between the groups in terms of the
severity of nausea; frequency of nausea, vomiting, retching or distress
caused by these symptoms on any follow-up days. According to these
results; both of our hypothesis, “H11 and H12 have been verified.
In the qualitative phase of the study, it was found that, according to
the statements of the participants, they became more independent in
such activities as going out to mosques, eating comfortably, doing the
housework and cooking and that they had more quality time after the
aromatherapy. The qualitative findings of this study support the quan­
titative findings.
Zorba and Özdemir31 formed three different groups (inhalation,
massage and control groups) which consisted of 25 patients who un­
derwent treatment with either adriamycin-cyclophosphamide or
cyclophosphamide-adriamycin-fluorouracil in a quasi-randomized
controlled study to compare the effects of massage and inhalation
aromatherapy on chemotherapy-induced acute nausea/vomiting. A
mixture of peppermint oil (2%), bergamot oil (1%) and cardamom oil
(1%) mixed with 100 ml of almond oil was smelled by patients in the
inhalation group. All the follow-ups in the study demonstrated that the
nausea severity of the control group was higher than that of the inha­
lation and massage groups, and the differences among the groups were
significant. Although the study of Zorba and Özdemir31 was conducted
in patients receiving the same chemotherapeutic agents, the effect of the
aromatic mixture only on acute nausea-vomiting was evaluated.
In the study carried out by Eghbali et al.,30 to evaluate the effect of
peppermint oil on CINV in patients with breast cancer in Iran, it was
determined that peppermint oil significantly reduces the frequency and
duration of acute nausea. However, it is reported the use of peppermint
oil leads to a reduction in frequency and duration of nausea and
vomiting in the delayed phase but not statistical significance. Similarly,
only peppermint oil was preferred in our study and its effectiveness was
followed for 5 days. In our study, it was found that peppermint oil is
effective in the delayed phase, also. But, Eghbali et al.,30 did not include
information about which chemotherapy regimen administered in their
study. Therefore, comments on the validity of the results remain up in
the air. The chemotherapy treatment protocols are handled separately
and compared among themselves in our study. This situation can be
expressed as the strength side of our study.
As for the study conducted by Seale,32 peppermint oil has been used
in 8 patients receiving palliative care to stem the tide of nausea and
vomiting. Results of this study showed that peppermint oil used in
conjunction with other medications did help relieve the nausea in the
eight patients included in the study. Even though the effectiveness of the
peppermint oil was stated in this study, the information on which
chemotherapy treatment patients received was not included and the
study was conducted in a quite small sample group.
In a recent study conducted with the participation of 79 patients, the
efficacy of a cool damp washcloth with peppermint essential oil versus
intensity of nausea in cancer patients was evaluated. The results of this
study demonstrated that the use of peppermint oil was effective in
decreasing the intensity of nausea experienced by patients compared to
using only a cool washcloth.33
Although studies are indicating that some aromatherapy applications
are not effective in the management of CINV, it has been concluded that
peppermint oil is effective in dealing with CINV in all studies using
peppermint oil. In addition to, there are not any reported adverse events
or side effects in the treatment of CINV which caused by the usage of
peppermint oil 8,28–33 However, in our study, two patients stated that
peppermint oil causes headache and three patients said that it increases

6
N. Efe Ertürk and S. Taşcı Complementary Therapies in Medicine 56 (2021) 102587

Table 4 the frequency and the severity of nausea. The peppermint oil practice
Distribution of INVR scale total score averages of the participants according to was discontinued after the first application in these patients. They
follow-up days and chemotherapy treatment protocol withdrew from the study. We are of the opinion that these symptoms
Chemotherapy Groups Total score averages of INVR according may have been associated with personal characteristics and the specific
treatment protocol to follow-up days ability of the sense of smell to stimulate memory and produce a range of
(Schedule) effects.43
1st day 2nd 3rd 4th
(M ± day day day
SD) (M ± (M ± (M ± 6. Conclusion
SD) SD) SD)

Intervention The results of this study reveal that one drop the peppermint oil
0.16 ± 0.43 ± 0.25 ± 0.14 ±
Folfirinox (Folinic Group (n =
0.20 0.62 0.44 0.27 applied to on the spot between their upper lip and their nose (on their
acid, fluorouracil, 14)
philtrum), three times a day for the five days following chemotherapy
irinotecan, and Control
oxaliplatin) Group (n =
0.73 ± 1.24 ± 1.52 ± 0.99 ± administration reduces the frequency of nausea, vomiting, and retching;
0.51 0.85 0.69 0.72 feelings of distress caused by these symptoms; and the severity of
16)

p*
<
0.007
< < nausea.
0.001 0.001 0.001
es** 1.37 1.05 2.13 1.49
Intervention 0.21 ± 0.40 ± 0.27 ± 0.00 ± 7. Suggestions
Paclitaxel- Group (n = 5) 0.21 0.46 0.22 0.00
Trastuzumab Control 0.38 ± 0.81 ± 0.92 ± 0.63 ± To increase the evidence-based results for in the CINV management,
Group (n = 9) 0.28 0.35 0.51 0.53
the effects of the peppermint oil or other essential oils on both acute and
p* 0.223 0.047 0.021 0.022
es** 1.06 1.47 1.47 delayed nausea and vomiting are recommended to investigated
Intervention 0.16 ± 0.36 ± 0.31 ± 0.01 ± considering the chemotherapy schedules.
Carboplatin AUC < 4 Group (n = 7) 0.25 0.37 0.32 0.04
-Paclitaxel Control 0.66 ± 1.12 ± 1.05 ± 0.63 ±
Group (n = 9) 0.59 0.62 0.59 0.45 Funding
p* 0.041 0.013 0.010 0.003
es** 1.05 1.42 1.50 1.81 This study is associated with the PhD thesis “The Effect of Peppermint
Intervention 0.16 ± 0.29 ± 0.30 ± 0.09 ± Oil Applied on Nausea, Vomiting and Retching in Patients Receving
Cyclophosphamide – Group (n = 6) 0.24 0.30 0.44 0.22
Adriamycin Control 0.63 ± 0.91 ± 0.98 ± 1.18 ±
Chemotherapy.” This study was approved and financially supported by
Group (n = 5) 0.19 0.38 0.47 1.10 the Unit of Scientific Research Projects of Erciyes University (project
p* 0.007 0.015 0.036 0.041 number: TDK-2017-7305).
es** 2.20 1.78 1.48 1.29
Intervention 1.14 ± 1.51 ± 1.78 ± 0.87 ±
Group (n = 4) 1.03 0.60 0.88 0.35 Authorship Statement
Cisplatin
Control 1.33 ± 2.11 ± 2.33 ± 1.10 ±
Group (n = 5) 1.02 0.51 0.33 0.39 All authors of this article have agreed on the final version of this
p* 0.784 0.156 0.229 0.407
paper and have met all of the following criteria; conception and design,
M ± SD, mean plus/minus standard deviation. acquisition of data, analysis and interpretation of data, drafting the
*
Independent-samples t-test was done. article, and revising it critically for important intellectual content.
**
Effect size (Hedges’ G).

Declaration of Competing Interest

Table 5
The qualitive data categorization The authors have no financial disclosures to declare and no conflicts
of interest to report.
Themes Subthemes Examples

Physical: Weakness; fatigue; “I wish I were dead. I

exhausted.
Experiencing post- Social: Loneliness; bornoud;
chemotherapy be detached from life.
nausea, vomiting and
retching Psychological: Death wish;
hate.
Physical: to feeling better as
physical
Effect of aromatherapy Social: to spending more
upon daily life time with family members
and friends; to increasing
self-efficacy.
Psychological: Relaxation;
feeling better.
Views about the effects
No idea; Spirituality
of aromatherapy
Easy and difficult sides
Easy; Enjoyment
of aromatherapy
cannot cook and I cannot CRediT authorship contribution statement
do the housework.” (D.Y.
female patient) Nuriye Efe Ertürk: Conceptualization, Methodology, Formal anal­
I continuously feeling ysis, Data curation, Investigation, Writing - original draft, Writing - re­
nausea and vomit so. I am
view & editing, Visualization. Sultan Taşcı: Conceptualization,
so weak. I could not caress
my kids’ head Methodology, Formal analysis, Investigation, Writing - review & editing,
I became able to go to Project administration, Funding acquisition.
mosque for Friday prayer. I
saw my friends and we had
a talk.” (L.A. male patient) Acknowledgements
I became able to eat. I was
able to complete my jobs. I The authors wish to thank the academic member Prof. Dr. Ahmet
Oztürk of the Biostatistics Department, Erciyes University Medical
even went shopping.” (Ş.A.
female patient)
Faculty, the academic member Prof. Dr. Ulvi Zeybek of the Pharma­
ceutical Botany Department, Ege University Pharmacy Faculty, the
I have no idea, only God personnel who working at the ambulatory chemotherapy unit, and all
knows (H.K. female participants for their support and participation in this trial.
patient)
I put it in my pocket and I
can use it even if I am Appendix A. Supplementary data
outside. It is not difficult.”
(İ.Ç. male patient).
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.ctim.2020.102587.

7
N. Efe Ertürk and S. Taşcı Complementary Therapies in Medicine 56 (2021) 102587

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