ANTI-EMETIC PROPHYLAXIS MEDICATION PATTERN FOR
CHEMOTHERAPY INDUCED NAUSEA VOMITING (CINV) IN PATIENTS WITH
SOLID TUMOR AT RAJAVITHI HOSPITAL
Kulaporn Wisit1,*, Krittika Tanyasaensook2,#, Montarat Thavorncharoensap3, Jedzada
Maneechavakajorn4, Jiraporn Chiaovit5,
1
Master of Science in Pharmacy Programme in Clinical Pharmacy (International Programme)
, Mahidol University, Thailand
2
Clinical Pharmacy Section, Department of Pharmacy, Faculty of Pharmacy, Mahidol
University, Thailand
3
Social and Administrative pharmacy Section, Department of Pharmacy, Faculty of
Pharmacy, Mahidol University, Thailand
4
Department of internal medicine, Rajavithi Hospital, Thailand
5
Department of Pharmacy, Rajavithi Hospital, Thailand
*e-mail: kwon_mome@hotmail.com, #e-mail: krittika.tan@mahidol.ac.th
Abstract
Background: Chemotherapy induced nausea and vomiting (CINV) is one of the most
discomfort and fear side effects. It interferes with patient’s nutritional status and affects daily
life of cancer patients. Several guidelines recommended the best effective antiemetic
prophylaxis medication; however, implementation of treatment recommendations is less than
usual. Objectives: The purpose of this study are to examine antiemetic medication pattern for
prevention of CINV according to guideline recommendation and to determine clinical
outcome of CINV and patient’s quality of life in breast and lung cancer patients at
ambulatory setting of Rajavithi Hospital. Method: This was a prospective descriptive study
in 34 patients from June to October 2013 composed of 82 % woman, with mean age of 55
year. Antiemetic use pattern were assessed according to developed criteria which based on
guideline recommendation of antiemetic medication for Rajavithi Hospital and
nausea/vomiting clinical outcome after receiving chemotherapy during first three cycles.
Result: Regarding pattern of antiemetic medications prescription, 5-10% and 60% of
prescription was inconsistence to the developed criteria for preventing acute phase and
delayed phase emesis, respectively. Nausea/vomiting clinical outcome in term of complete
response (no emetic episode and no use of rescue medication; CR) indicated a better control
in acute phase than delayed phase emesis with approximate 85% and 50% of patients can
achieved CR. However, comparing in the group that received consistency and inconsistency
antiemetic medication found not significantly difference in CR percent. Nevertheless, almost
half of patients still experience delayed emesis and associated symptoms of nausea with
impact on their quality of life. Conclusion: Despites many antiemetic guideline
recommendations, CINV remains a significant problem in cancer patients, particularly
delayed phase emesis after received chemotherapy which impact their quality of life and may
avert patients from continuing cancer treatment. CINV continue importance targets for
developed the method to subside this problems.
Keywords: chemotherapy-induced nausea and vomiting, anti-emetic medication, supportive
care, cancer
Introduction
Chemotherapy medication is the therapy that usually used to treat cancer patients.
These treatments target any rapidly dividing cells not only cancer cells but also normal cells.
Therefore, cancer patients have to face common acute or long-term side effects such as hair
loss, nausea, vomiting, and fatigue. Moreover, some side effects such as neutropenia, anemia
and thrombocytopenia can lead to other serious problems like infection and bleeding. Some
mild adverse reactions can also cause patients feel distress and uncomfortable which
consequence to anxiety about chemotherapy treatment. Because of these adverse reactions
from chemotherapy, health care professional not only treat just cancer disease but also have
to take care adverse effects from chemotherapy.
Nausea and vomiting are common symptoms among cancer patients as a result of
either chemotherapy-related toxicity or complications directly or indirectly related to the
cancer. These symptoms are some of the most distressing and disturbing side-effects of
cancer treatment. Regardless of the etiology, the symptoms of nausea and vomiting can
interfere with patients’ nutritional status and their enjoyment of eating and drinking and can
significantly impact their quality of life which may avert patients from continuing cancer
treatment. Incidence and severity of chemotherapy induced nausea and vomiting (CINV) are
related to several factors, most notably the emetogenic risk of the chemotherapy (related to
the specific drug, dose, schedule, and route of administration) and patient variability.1,2,7
Overall, approximately 50-60 percent of cancer patients on chemotherapy experience nausea
and/or vomiting.3 Moreover, a negative experience with these symptoms leads to the
subsequent impact of 10 to 44 percent of patients experiencing anticipatory nausea and/or
vomiting.4 For evidences from international and Thailand, nausea and vomiting is one of ten
most common adverse drug reactions found in cancer patients.5,6 Fortunately, these
symptoms can be preventable with prophylactic antiemetic therapy which is more effective in
prevention and management in this advanced’ age. Therefore, nausea and vomiting need to
be appropriately prevented, screened, assessed, treated, and followed up to ensure the best
care.
The American Society of Clinical Oncology (ASCO) 1999 and 20118-9, National
Comprehensive Cancer Network (NCCN) 201210 and Multinational Association of
Supportive Care in Cancer (MASCC) 201111-12 are major guidelines in supportive care that
recommend the prevention of CINV. The goal of each antiemetic medication is to prevent
nausea and vomiting during both acute phase (0-24 hours after receive chemotherapy) and
delayed phase (24-120 hours after receive chemotherapy). Treatment guidelines are
beneficial tools that enable physician to integrate recommendation into their practices.
However, integration of recommendation into real practice has to concern about availability
and policy of antiemetic medication in their hospital. Despite the availability of guideline
recommendation, however, there is evidence that adherence to and implement of antiemetic
recommendation are less than usual. Cause of these may stem from afraid of some side effect
of antiemetic medication or misinformation about clinical outcome of nausea and vomiting of
patients after received chemotherapy. In some case, patients were nonadherent to antiemetic
medication because of lack of understand on how to use this medication.13,14
For Rajavithi Hospital which is approximate 1,200 beds tertiary care hospital,
oncology care service is one of service in these hospitals which approximately 2,500 cancer
patient per year. Antiemetic prescription in this hospital is varied and depended on individual
physician. In some case, antiemetic prescriptions are not concordance with guideline
recommendation which may cause cancer patients having more nausea and vomiting side
effect at home. The purpose of this study are to examine antiemetic prophylaxis medication
pattern for prevention of CINV according to guideline recommendation and to determine
clinical outcome of CINV and patient’s quality of life in cancer patients with solid tumor
treated at outpatients setting of Rajavithi Hospital. The result of this study may be used as the
basic information for developing the institutional guideline for preventing and managing
CINV in cancer patients.
Methodology
Patients and Methods
Study design
The study is designed as a prospective descriptive study which conducted at
ambulatory oncology unit at Rajavithi Hospital. The study was performed approximately 5
months during June to October 2013. Study protocol was approved by the Faculty of
Dentistry/Faculty of Pharmacy Mahidol University Institutional Review Board (MU-DT/PYIRB) and Human Research Ethic Committee of Rajavithi Hospital. The following
demographic and clinical data were collected in collecting data form for each patient: age,
gender, type and stage of disease, type and dose of chemotherapy agents administered,
history of nausea and vomiting, dose and regimen of antiemetic treatment, and rescue
medication received.
Patients with breast cancer or lung cancer patients either of chemotherapy-naïve or
non naïve patients with age of 18-80 years old who visit ambulatory oncology clinic and
received high to moderate emetogenic risk chemotherapy or treatment regimen which are
composed of CAF regimen (cyclophosphamide 500 mg/m2, doxorubicin 50 mg/m2, and 5-FU
500 mg/m2), AC regimen (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2) and
platinum compound based regimen at Rajavithi Hospital were invited to participate. Each
patient had to have scheduled to receive the first cycle and at least 4 consecutive cycles of
chemotherapy or treatment regimen at ambulatory oncology unit, Rajavithi Hospital.
Exclusion criteria were patients who have uncontrolled concurrent illness other than
neoplasm, symptomatic brain metastases that affects cognitive function, other cause of
nausea and vomiting, abnormal memory or partial to complete hearing loss which were
confirmed in medical record, or inability to understand or complete the self-monitoring tools.
All patients provided written informed consent
Drop out condition was considered in patients who loss to follows up for at least two
consecutive visits, not cooperated with self-monitoring procedure. Termination from the
study was considered in patients who have tumor progression, who died from any cause
during period of study, patient’s decision to terminate from the study, who have serious
adverse reaction from cancer treatment that requires intensive care treatment and who have
serious side effects from antiemetic medications or patient’s underlying diseases interact with
antiemetic medications that cause changes in medication from the developed criteria.
Assessment tool
Criteria of antiemetic prophylaxis of CINV in oncology patients were developed
according to current guideline recommendations, relevant articles and textbooks (table 1).
The major guidelines in supportive care were from American Society of Clinical Oncology
(ASCO) 1999 and 20118-9, National Comprehensive Cancer Network (NCCN) 201210 and
Multinational Association of Supportive Care in Cancer (MASCC) 2011.11-12 Beside the
major guidelines, these criteria was also considered the best antiemetic medications that
available in Rajavithi Hospital. The criteria were utilized to determine the consistency of
antiemetic medication prescription to developed guideline recommendation.
Education materials for participants were composed of Rajavithi Hospital’s booklet
for self-handling of chemotherapy side effects and booklet for self-monitoring of
nausea/vomiting. Self-monitoring tool were consisted of recording forms about frequency
and severity of nausea and vomiting at home for 5 days which cover the acute phase and
delayed phase of nausea and vomiting. Using of adverse effect monitoring tool can enhance
the ability of patient and provider to evaluate adverse drug reactions. Participants were given
both oral and written instructions by researcher pharmacist on the self-monitoring of nausea
and vomiting and on the documentation of the antiemetic medications prescribed.
The European Organization for Research and Treatment of Cancer Quality of Life
Queationnaire-C30 (EORTC QLQ-C30) developed by the EORTC was used to assess quality
of life of participants in this study. This questionnaire was translated into many languages
and used in various countries including Thai language version.15 The EORTC QLQ-C30 is
composed of both multi-item scales and single-item measures account for 30 questions.
These include five functional scales, three symptom scales, a global health status / QoL scale,
and six single items; each individual item is scored as patient’s response mark in four-point
scales, namely “Not at all”, “A little”, “Quite a bit” and “Very much”. The EORTC QLQC30 in Thai language is already asked for permission to use in this study from EORTC data
center. All participants were received a telephone call from the researcher pharmacist on days
2 and 7 after treatment to ensure that the collection of data was completed and interviewed
quality of life on day 7 after treatment.
Table 1 Criteria for prevention of chemotherapy induced nausea and vomiting (CINV) in adult based on emesis
risk category for Rajavithi Hospital
Phase
Acute phase
High emetogenic risk
Ondansetron 8-16 mg IV or
PO or 0.15 mg/kg IV
(max 32mg)
+ dexamethasone 20 mg IV
Moderate emetogenic risk
Ondansetron 8-16 mg IV or
PO or 0.15 mg/kg IV
(max 32mg)
+ dexamethasone 8-12 mg
PO or IV
Delayed phase
Dexamethasone 8 mg oral
BID day 2-4
(± metoclopramide 30-40 mg
PO two to four times per day
for 2-3 days)
± lorazepam 0.5-2 mg PO
every 4-6 hr day 1-4
± H2 blocker or PPI
dexamethasone 8 mg PO
(4mg BID) or IV
OR ondansetron 8mg BID or
16 mg OD or 8 mg IV
± metoclopramide 10-40 mg
PO or IV every 4 or every 6
h PRN
± lorazepam 0.5-2 mg PO
every 4-6 hr day 1-4
± H2 blocker or PPI
Low emetogenic risk
dexamethazone 4-12 mg PO
or IV (recommend 8 mg)
OR metoclopramide 10-40
mg PO or IV
OR prochlorpermazine 10
mg PO or IV
No routine prophylaxis
OR metoclopramide 10-40
mg PO or IV every 4 or
every 6 h PRN
(OR domperidone )
± lorazepam 0.5-2 mg PO
every 4-6 hr day 1-4
± H2 blocker or PPI
Study method
Breast cancer or lung cancer patients either of chemotherapy-naïve or non naïve
patients who visit ambulatory oncology clinic were screened according to inclusion and
exclusion criteria and were invited to participate. The medical charts of the participants are
reviewed as follows: patient’s demographic data, history of allergy, concomitant underlying
diseases, concurrent medications, type of cancer and staging, chemotherapy regimen , history
of nausea and vomiting, dose and regimen of antiemetic treatment for acute phase and
delayed phase, and rescue medications received. Consistency of antiemetic treatment was
determined by criteria of antiemetic prophylaxis medications that developed for Rajavithi
Hospital. Participants were received the Rajavithi Hospital’s booklet for self-handling of
chemotherapy side effects and the booklet of self-monitoring tool for nausea and vomiting.
Participants were described to record the episode, frequency and severity of nausea and
vomiting and antiemetic medication that they took in self-monitoring tool for 5 day. The
activities, takes about 5-10 minutes/person, were performed while patient was waiting for
chemotherapy administration or receiving chemotherapy. Each participant was followed up
for 3 more consecutive times in the second, third and fourth visit for chemotherapy
(according to each type of cancer treatment) to monitor nausea and vomiting experience from
the previous chemotherapy cycle and record data in the self-monitoring tool which patients
brought back on follow-up day. All participants were followed up via telephone after 1 day
and 1 week to motivate recording nausea and vomiting side episodes and figure out any
problem in self-monitoring tool and were interviewed via telephone about quality of life
using EORTC QLQ-C30 Thai version questionnaire at 1 week after received the first and
third cycle of chemotherapy. The study was end at fourth visit for chemotherapy of each
patient.
Assessment method
Consistency to antiemetic criteria was defined as physician prescription concordance
with the developed criteria regarding of type of antiemetic medication, dosage regimen and
duration of prophylaxis. If the prescription is not concordance with the developed criteria, it
will be considered as inconsistency antiemetic prescribing.
Assessment of nausea/vomiting episode and severity; emetic episode was defined as
one episode or a sequence of episodes of vomiting in very close succession not relieved by a
period of relaxation of at least 1 minute; any number of unproductive emetic episodes
(retches) in any given 5 minute period; or an episode of retching lasting <5 minutes combined
with vomiting not relieved by a period of relaxation of at least 1 minute. Nausea episode was
a symptom of emetogenic stimuli not significant enough to cause vomiting. Physiological
symptoms of nausea can include cold sweating, tachycardia, GI upset, and hypersalivation.
Nausea and emetic severity was graded by self-assessment on 5- Likert scale ranged from 1
to 5 which corresponding to very mild (1) to very severe (5), respectively.
Clinical outcome variables in this study were accessed in terms of:
Primary outcome: Complete response (CR) was defined as no emetic episode and no
use of rescue medication in periods of 24 hours and 5 days after received chemotherapy that
cover acute and delayed emesis, respectively
Secondary outcome:
Complete control (CC) was defined as no emetic episode, no need for rescue
medication and no more than mild nausea (or measure from Likert scale ≤ 2) in periods of 24
hours and 5 days after received chemotherapy. Health related quality of life measured by
EORTC QLQ C-30 version 3.0 questionnaires in Thai language, a quality of life instrument
for cancer patients.
Statistical analysis
The demographic characteristics of patients were analyzed by using descriptive
statistics. Chemotherapy and antiemetic agents received by patients, consistency of
antiemetic medication to developed criteria and episodes and severity of nausea and vomiting
were described using counts and percentages. CR and CC were described as proportion of
participants achieves complete response or complete control in periods of 24 hours and 5
days after each chemotherapy cycle. Quality of life assessed by EORTC QLQ-C30 was
described as scores and percentage in each scale (global health status/QOL scale functional
scales, symptoms scales). Clinical outcome of patients who received consistency and
inconsistency antiemetic medications were compared by Fisher’s exact test and difference of
quality of life in each scales were compared by paired-T test using the Statistical Package for
Social Sciences (SPSS) program version 21.0. Statistically significant level was considered at
P-value <0.05.
Result
Patient’s characteristics
From June to October 2013, 34 patients were participated in this study. There were 31
patients (91.2%) receiving chemotherapy for the first time, while 3 patients (8.8%) had
experience with chemotherapy at least 1 cycle prior to the study. Most study population were
women (82.4%) with mean patient age of 55 years (SD11.9).
Chemotherapy agent
Fifty-eight percent of participants were diagnosed as breast cancer, the rest was lung
cancer. Paclitaxel/carboplatin (PT) was the most common treatment (32.3%) in this study
followed by cyclophosphamide/doxorubicin/5-FU (CAF) regimen (29.4%), doxorubicin
/cyclophosphamide (AC) regimen (29.4%), and carboplatin/etoposide regimen (8.8%). About
58.8% and 41.2% of all patients were classified as having been treated with highly (HEC)
and moderately (MEC) emetogenic chemotherapy regimens, respectively. Table 2
Table 2 Patients characteristics and chemotherapy agents administered
Patients characteristics
Number (%)
Sex
Male
Female
Age (year)
< 40
40-49
50-59
60-69
> 70
Mean age 55 ± 11.9
Previous history of chemotherapy
Chemotherapy naïve
Chemotherapy non naïve
Cancer type
Breast cancer
Lung cancer
Cancer staging
Stage 2
Stage 3
Stage 4
Common chemotherapy regimen
Doxorubicin /Cyclophosphamide (AC) regimen
Cyclophosphamide/Doxorubicin/5-FU (CAF) regimen
Paclitaxel/Carboplatin (PT) regimen
Carboplatin/Etoposide regimen
Emetogenicity level
Highly emetogenic chemotherapy (HEC)
Moderately emetogenic chemotherapy (MEC)
6 (17.6)
28 (82.4)
5 (14.7)
6 (17.6)
10 (29.4)
8 (23.5)
5 (14.7)
31 (91.2)
3 (8.8)
20 (58.8)
14 (41.2)
12 (35.3)
8 (23.5)
14 (41.2)
10 (29.4)
10 (29.4)
11 (32.3)
3 (8.8)
20 (58.8)
14 (41.2)
Risk factors for CINV
Most patients had at least one risk factor of CINV. Most of it was no alcohol drinking
(94.1%), female gender (82.4%), younger age (32.3%), having experience of nausea and
emesis during pregnancy (29.4) or from previous chemotherapy (8.8%).
Antiemetic medications and concordance to developed criteria
All patients (100%) received dexamethasone and ondansetron as antiemetic
medications for prevention of acute phase emesis in both HEC and MEC risk. In delayed
phase, ondasetron with metoclopramide were the most common antiemetic medications
(38.2%) for first to third cycle of chemotherapy, followed by ondansetron with domperidone
(27.5%), domperidone alone (13.7%), metoclopramide alone (12.7%), dexamethasone with
ondansetron and metoclopramide (5.9%) and dexamethasone with ondansetron and
domperidone (2%) (Table 3). Rescue therapies consisted of metoclopramide and
domperidone with, in a few cases, a 5-HT3 receptor antagonist added to the regimen.
Table 3 Common antiemetics for prevention of delayed phase emesis
Antiemetic medications
Cycle 1
Cycle 2
Number (%)
Number (%)
Dexamethasone + ondansetron +
metoclopramide
2 (5.9)
3 (8.8)
Dexamethasone + ondansetron +
domperidone
0 (0)
1 (2.9)
Ondansetron +metoclopamide
15 (44.1)
13 (38.2)
Ondansetron + domperidone
9 (26.5)
10 (29.4)
Metoclopramide
1 (2.9)
3 (8.8)
Domperidone
7 (20.6)
4 (11.8)
Cycle 3
Number (%)
All cycle
Number (%)
1 (2.9)
6 (5.9)
1 (2.9)
11 (32.3)
9 (26.5)
9 (26.5)
3 (8.8)
2 (2)
39 (38.2)
28 (27.5)
13 (12.7)
14 (13.7)
Regarding the concordance to the developed criteria, almost antiemetic medications
for prevention acute phase emesis was consistent to the criteria for patients received HEC and
MEC (90-100%), in a few case that inconsistence because of concordance of dosage regimen.
In delayed phase, though, prescribed antiemetics for prevention were mostly inconsistent to
the criteria (~60%), especially in first cycle of chemotherapy of patients received HEC.
Cause of inconsistency came from discordance in type of antiemetic medications and dosage
regimen (Table4).
Table 4 Consistency of antiemetic medications to the criteria
Type of emesis
Percentage of consistency to the criteria
Cycle 1
Cycle 2
Cycle 3
High emetogenicity level
Acute phase
95
100
90
Delayed phase
5
45
45
Moderate emetogenicity level
Acute phase
100
100
100
Delayed phase
42.6
57.1
78.6
Control of Nausea and emesis
Percentage of patients achieved complete response (CR) in acute phase was 85.29,
85.29 and 82.35 for first cycle, second cycle and third cycle of chemotherapy, respectively. In
delayed phase, percentage of patients achieved CR was 44.12, 55.88 and 73.53 for first cycle,
second cycle and third cycle of chemotherapy, respectively (Figure 1). In term of complete
control (CC), percentage of patients achieved CC was also the same direction as percentage
of patients achieved CR with lower percentage (Figure 2). Severity of nausea was mostly
very mild severity in both acute phase and delayed phase, except in some cases, severity was
considered as severe (8%) (Figure 3). Severity of emesis was mostly very mild to mild
severity in both acute phase and delayed phase, although, in some cases, severity was
considered as severe to very severe (25%) (Figure 4).
Figure 1 Percentage of patients achieved complete
response (CR) in acute phase and delayed phase
Figure 2 Percentage of patients achieved complete
control (CC) in acute phase and delayed phase
Figure 3 Severity of nausea in acute phase and delayed Figure 4 Severity of emesis in acute phase and delayed
phase in 5-Likert scale from very mild to very severe
phase in 5-Likert scale from very mild to very severe
Association of nausea/emesis clinical outcome and consistency of antiemetic prescriptions
In acute phase, those patients were mostly received consistent antiemetic medication,
were achieved CR approximately 75-80% and 100% in HEC group and MEC group,
respectively. In delayed phase, when consider in term of consistency and CR, both of patients
in HEC and MEC group who received consistent antiemetic medications had higher
percentage of patients achieved CR when compare to the group that received inconsistency
antiemetic medication in first cycle, second cycle and third cycle of chemotherapy (Table 5).
However, the difference of percentage of CR in consistency and inconsistency antiemetics
group was not statistical significantly in both HEC and MEC (P>0.05).
Table 5 Complete response (CR) in delayed phase emesis according to consistency to the criteria
Consistency to the criteria
% CR Cycle 1
% CR Cycle 2
% CR Cycle 3
(P-value)
(P-value)
(P-value)
High emetogenicity level
Consistency
100 (0.4*)
66.67 (0.09*)
88.89 (0.058*)
inconsistency
36.8
27.27
45.45
Moderate emetogenicity level
consistency
50 (0.5*)
75.00 (0.59*)
90.91 (0.396*)
inconsistency
50.00
66.67
66.67
* Fisher’s exact test at P-value <0.05
Assessment of impact on quality of life
Mean scores for global health status of all patients represented a high quality of life in
first cycle and third cycle (69.36 ± 14.61 and 68.39 ± 16.76, respectively). In functional
status, the higher score also represented healthy level of functioning (91.44 ± 9.81and 93.86 ±
6.31, respectively). The mean symptom scales obtained for nine items of questionnaire were
20.65 ± 9.18 and 23.07 ± 22.06 in first cycle and third cycle of chemotherapy, respectively.
These low scores indicated low levels of symptomatology/problems. In particular, nausea and
vomiting symptom scales was also show low scores, indicated low levels of problem with
approximate 25%. When stratified in each emetogenicity level, nausea/vomiting symptom
scales showed higher scores in HEC group (Table 6).
Table 6 Quality of life measured by EORTC QLQ-C30 in first and third cycle of chemotherapy
QOL
Global health status Functional status
Symptom status
N/V symptom (%)
(%)
(%)
(%)
High emetogenicity level*
Cycle 1
69.58 ± 13.04
91.79 ± 7.31
20.36 ± 9.48
28.33 ± 23.00
Cycle 3
67.93 ± 14.37
95.33 ± 3.94
19.74 ± 14.12
22.50 ± 23.11
Moderate emetogenicity level*
Cycle 1
69.05 ± 17.12
90.95 ± 6.25
21.06 ± 9.06
20.24 ± 17.51
Cycle 3
69.05 ± 20.26
91.75 ± 8.38
27.82 ± 30.04
14.29 ± 17.12
Total *
Cycle 1
69.36 ± 14.61
91.44 ± 9.81
Cycle 3
68.39 ± 16.76
93.86 ± 6.31
*Paired-T test; not significant difference at P <0.05
20.65 ± 9.18
23.07 ± 22.06
24.99 ± 21.02
19.12 ± 20.97
Discussion
Nausea and vomiting side effect are one of the most distresses and worry side effect
from chemotherapy. These cause cancer patients feel discomfort during cancer treatments,
especially in patient who received high to moderate emetogenic level chemotherapy, such as
in breast cancer and lung cancer. For prevention these side effect, delivering effective
antiemetics and good knowledge of self-management are the best tools to resolve these
problems. Antiemetic prophylaxis guidelines recommended the latest clinical research of
effective antiemetic medication that physician enable to integrate into their practices.
However, despite many guidelines recommendation, there is evidence that adherence to and
implementation of treatment recommendations is less than optimal.14-15
In this study, most patients were chemotherapy naïve who diagnosed as breast cancer
and received HEC, while lung cancer patients received MEC (carboplatin). Most patients had
at least one risk factor of CINV, especially female gender and younger age that are the most
influence risk factor for CINV, which make these patients, have more tendencies to develop
nausea and vomiting side effect. Antiemetic prophylaxis criteria that developed were
considered the best antiemetic medications that many international guidelines recommended
and also the most effective drug available in Rajavithi Hospital. Because of Rajavithi hospital
did not have aprepitant and palonosetron which are the most effective antiemetic medication
according to guideline recommendations10-13, so corticosteroids (dexamethasone) with
conventional 5-HT3 antagonist receptor (ondansetron) were recommended to prevent acute
phase CINV, dexamethasone with/without dopamine antagonist receptor (metoclopramide)
were recommended to prevent delayed phase CINV in HEC and dexamethasone or
ondansetron with/without metoclopramide was recommended to prevent delayed phase CINV
in MEC.
Regarding the concordance to the developed criteria for prevention of CINV for
Rajavithi hospital, almost antiemetic medications for prevention acute phase emesis was
consistent to the criteria, but not for delayed phase prevention. Most of prescribed antiemetics
for prevention of delayed phase emesis were considered as low effective to control CINV.
Underuse of high effective antiemetics may come from many reasons like worry about side
effects of antiemetics such as hyperglycemia from dexamethasone, constipation from 5-HT3
antagonist and extrapyramidal system syndrome and dizziness from metoclopramide. Despite
a high rate of inconsistency of antiemetics for delayed phase, the CR and CC of nausea and
emesis outcome were also higher than 40 percent; it is not significantly difference from
another group that received consistent antiemetic medication. However, when consider in
percentage of CR, the group that received consistency antiemetics showed higher percentage
than the group that received inconsistency antiemetics, especially in HEC patients. The
higher percentage of CR in group that received inconsistency antiemetic medication may be
attributed to patient’s self-management and self-learning after received chemotherapy.
Nevertheless, some patients also suffered from moderate and severe nausea and vomiting,
which cause anticipatory emesis in next cycle of chemotherapy and also worry about cancer
treatment.
The result of quality of life measured by EORTC-QLQ-C30 in Thai version showed
well quality of life and functional of living which was not difference during the first and third
cycle of chemotherapy. However, in the third cycle, levels of symptomatology/problems and
nausea/vomiting side effect tended to decline. Beside nausea/vomiting side effect,
constipation, myalgia, dyspepsia, loss appetite, dizziness, fatigue and flatulence were
common complained side effects.
The present study was carried out in ambulatory setting and recruited just breast and
lung cancer patients. As such, it may be lack of a diverse and heterogeneous patient
population. Moreover, because of this study performed at ambulatory setting the possibility
that patients received HEC was less than normal, such as use of carboplatin (MEC) instead of
cisplatin (HEC) medication as platinum compound based regimen for lung cancer treatment.
Therefore, the incidence and severity of nausea and vomiting may be tending to increase.
From this study, there is still a need to educate health care professionals regarding the
distinction between prevention of acute and delayed CINV in routine practice, especially in
delayed phase CINV that usually happen out of hospital causing decrease quality of life of
cancer patients. Knowledge about the different types, risk of emesis and their most effective
and available treatment may represent a resource for improvement. However, this study had
several limitations such as small sample and not heterogeneous which could not represents
patients population, this need further study in more group of patients and in a routine clinical
practice setting including outpatients and inpatients. Moreover, it needs further improvement
in interesting design and impact of used developed criteria of antiemetic medication and
provided patients education to improve nausea/vomiting outcome.
Conclusion
The results of this study indicate that despite many antiemetic guideline
recommendations, adherence to treatment recommendations is less than expected,
particularly those for prevention of delayed phase emesis. Controlling of nausea and vomiting
in term of complete response (CR) indicate a better control in acute phase than delayed phase
emesis with approximate eighty-five percent and fifty percent of patients can achieve CR in
acute phase and delayed phase emesis, respectivly. Mean quality of life score indicated good
quality of life and functional of living with little level of problem. However, almost half of
patients still suffer from delayed emesis and associated symptoms of nausea that might
impact on their quality of life.
References
1.
Naeim A, Dy SM, Lorenz KA, Sanati H, Walling A, Asch SM. Evidence-based recommendations for
cancer nausea and vomiting. J Clin Oncol 2008 Aug 10; 26(23): 3903-10.
2. Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med 2008; 358(23):2482-94.
3. Grunberg SM, Deuson RR, Mavros P, Geling O, Hansen M, Cruciani G, et al. Incidence of chemotherapyinduced nausea and vomiting after modern antiemetics. Cancer 2004;100: 2261-68.
4. Morrow GR, Lindke J, Black PM. Predicting development of anticipatory nausea in cancer patients:
Prospective examination of eight clinical characteristics. J Pain Symptom Manage 1991;6:215-223.
5. Ob-oun T, Kopol J, Phosahut P, Thirasirawate S, Chisong C, Phumart P, et al. Adverse drug reaction
monitoring and counseling in oncologic patients at Mahasarakham Hospital. In the 4th Annual Northeast
Pharmacy Research Conference 2012 “Pharmacy Profession in Harmony” Faculty of Pharmaceutical
Sciences, Khon Kaen University, Thailand.
6. Lau PM, Stewart K, Dooley M. The ten most common adverse drug reactions (ADRs) in oncology
patients: Do they matter to you. Support Care Cancer 2004;12:626–33.
7. Bayo J, Fonseca PJ, Hernando S, Servitja S, Calvo A, Falagan S, et al. Chemotherapy-induced nausea and
vomiting: Pathophysiology and therapeutic principles. Clin Transl Oncol 2012;14(6):413-22.
8. Gralla RJ, Osoba D, Kris MG, Kirkbride P, Hesketh PJ, Chinnery LW, et al. Recommendations for the use
of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin
Oncol 1999;17(9):2971-94.
9. Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al. Antiemetics: American
Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011;29(31):4189-98.
10. National Comprehensive Cancer Network (NCCN). Antiemesis. Version1, 2012. Available from:
http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed date 17 Jul 2012.
11. Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, et al. Guideline update for MASCC and
ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the
Perugia consensus conference .Ann Oncol 2010;21(5):232–43.
12. Gralla R, Roila F, Tonato M, Herrstedt J. MASCC/ESMO antiemetic guideline 2011. [Online]. Available
from: http://www.mascc.org/assets/documents/MASCC Guidelines_English_2011.pdf. Accessed date 17
Jul 2012.
13. Jansing T, Vitayakul P, Prasertsup S and Cheimongkol W. Antiemetic effects for chemotherapy-Induced
acute nausea and vomiting in Sawhanpracharuk Hospital. Thai Pharm Health Sci J 2008;4(1):52-59
14. Chan A, Low XH and Yap K. Assessment of the relationship between adherence with antiemetic drug
therapy and control of nausea and vomiting in breast cancer patients receiving anthracycline-based
chemotherapy. J Manag Care Pharm. 2012;18(5):385-94
15. Sirisinha T, Ratanatharathorn V, Jirajarus M, Sirilerttrakul S, Silpakit C, Sirachainan E, et al. The
European Organization for Research and Treatment of Cancer quality of life questionnaire: Translation and
reliability study of the Thai version. J Med Assoc Thai 2002;85:1210–19.