Ij

This material is protected by U.S. copyright law. Unauthorized reproduction is prohibited. To purchase quantity reprints,
please e-mail reprints@ons.org or to request permission to reproduce multiple copies, please e-mail pubpermissions@ons.org.
ONLINE EXCLUSIVE
Delayed Chemotherapy-Induced Nausea
in Women Treated for Breast Cancer
Suzanne L. Dibble, RN, DNSc, Jill Israel, BSN, RN, Brenda Nussey, BA,
Karen Casey, MS, RN, ANP, and Judith Luce, MD
Key Points . . .
Purpose/Objectives: To describe the experience and intensity of de-
layed nausea in women undergoing chemotherapy for breast cancer
since the advent of the 5-HT3 antagonists.
Delayed nausea is a significant problem for the majority (73%
Design: Multisite, longitudinal, descriptive.
82%) of women receiving chemotherapy for breast cancer.
Setting: 7 outpatient oncology clinics situated in hospitals, 5 outpa-
For women who suffer from delayed nausea, days two through
tient oncology clinics associated with major teaching universities, 27
four are the worst.
private outpatient oncology practices, and 1 outpatient clinic located in
Older women experience less severe chemotherapy-induced
a county hospital.
Sample: Typical participants (N = 303) were 51.9 years old, Cauca-
delayed nausea.
sian (79%), married or partnered (65%), born U.S. citizens (92%), het-
Women diagnosed with breast cancer who have a history of
erosexual (96%), living with someone (83%), and high school graduates
nausea with stress experience more severe chemotherapy-in-
(82%).
duced delayed nausea.
Methods: Baseline and poststudy questionnaires plus a daily diary of
nausea through two cycles of chemotherapy (approximately two months)
were used to collect data. The Rhodes Inventory of Nausea, Vomiting,
the discontinuation of potentially effective treatment strategies
and Retching was used to assess the nausea experience.
Main Research Variables: Nausea.
(Rhodes & McDaniel, 1997). Approximately 10%15% of pa-
Findings: The worst nausea occurred on the third day after having
tients may refuse or delay their chemotherapy treatments be-
chemotherapy for breast cancer. The types of oral antiemetics ordered
cause of fears about N&V (Pendergrass, 1998).
for home use were changed between the two cycles of the study only
Nausea is a protective reflex against the ingestion of toxins
8% (n = 24) of the time. Younger, heavier women experienced more de-
and is defined as a subjective phenomenon of an unpleasant
layed nausea. Women who had a history of nausea with stress and
sensation in the epigastrium and in the back of the throat that
women receiving cyclophosphamide experienced more delayed nausea
may or may not culminate in vomiting (Rhodes & McDaniel,
during both time periods.
1997). Vomiting is the "mechanical result of neurophysiologi-
Conclusions: Delayed nausea is a significant problem for women re-
cally induced rhythmic, coordinated, diaphragmatic, chest
ceiving chemotherapy for breast cancer.
wall and abdominal muscle action leading to expulsion of
Implications for Nursing: Oncology nurses can use the results from
this study to provide anticipatory guidance for patients undergoing che-
gastric contents through the mouth" (Fessele, 1996, p. 1410).
motherapy for breast cancer.
N&V during chemotherapy is distinguished as anticipatory,
acute, or delayed. Acute N&V occurs within 24 hours of the
Suzanne L. Dibble, RN, DNSc, is a professor, Jill Israel, BSN, RN,
n estimated 211,300 women will be diagnosed with
A
is a research associate, Brenda Nussey, BA, is a programmer ana-
breast cancer in 2003, 32% of all new cancer cases
lyst, and Karen Casey, MS, RN, ANP, is a research associate, all in
this year (American Cancer Society, 2003) . Most, if
the Institute for Health and Aging at the University of California, San
not all, of these patients will receive chemotherapy. Two of the
Francisco. Judith Luce, MD, is a professor in the School of Medicine
side effects of chemotherapy, nausea and vomiting (N&V), re-
at the University of California, San Francisco. Support for this study
main a major worry for patients who are undergoing treatment
was received from the ONS Foundation. This research was funded
for breast cancer. The positive relationship between survival
by the ONS Foundation Center for Leadership, Information, and Re-
from breast cancer and the completion of a full course of chemo-
search through an unrestricted grant from SmithKline Beecham.
therapy demonstrates the necessity for compliance with treat-
(Submitted July 2002. Accepted for publication November 2, 2002.)
(Mention of specific products and opinions related to those products
ment. Some patients experiencing postchemotherapy N&V will
do not indicate or imply endorsement by the Oncology Nursing Fo-
withdraw from seemingly beneficial treatment (Fessele, 1996;
rum or the Oncology Nursing Society.)
Osoba et al., 1997). Patients have indicated that nausea contrib-
utes to their reluctance to begin chemotherapy and can result in
Digital Object Identifier: 10.1188/03.ONF.E40-E47
ONF VOL 30, NO 2, 2003
40
administration of chemotherapy, and delayed N&V occurs
or without metoclopramide. For patients who are receiving
moderately emetogenic regimens, 5-HT3 receptor antagonists do
after the first 24 hours. Anticipatory N&V occurs not from the
not appear to be effective in controlling delayed N&V, resulting
stimulus of the chemotherapy, but in anticipation of receiving
in a 22%89% incidence of delayed N&V (Italian Group for
it. The focus of this article is delayed nausea associated with
Antiemetic Research, 2000; Uyl-de Groot, Wait, & Buijt, 2000).
chemotherapy administration.
Initial studies of 5-HT3 antagonists, their interpretation by
Chemotherapy for breast cancer consists of the following
standard chemotherapy regimens: cyclophosphamide, methotr-
clinicians, and the observation of women as they underwent
exate, and fluorouracil (CMF) and cyclophosphamide and
chemotherapy suggested that acute vomiting almost has been
doxorubicin with or without fluorouracil (CA or CAF) and with
eliminated from the acute side affects associated with chemo-
or without paclitaxel (CAT, CAFT). Although these are consid-
therapy administration, with control rates of 75%90% (Uyl-
ered mildly to moderately emetogenic, significant incidence of
de Groot et al., 2000). Information about the incidence and in-
N&V occurs with these regimens (Goodman, 1997; Greene,
tensity of delayed nausea was not clearly delineated during the
Nail, Fieler, Dudgeon, & Jones, 1994; Stewart, 1996). Delayed
past decade. Therefore, the purpose of the current study was
chemotherapy-induced nausea particularly is associated with
to describe the delayed nausea experience and intensity in
CA (National Comprehensive Care Network [NCCN], 2001).
women undergoing chemotherapy for breast cancer since the
Patients who experience N&V within the first 24 hours af-
advent of the 5-HT3 antagonists.
ter receiving chemotherapy are significantly more likely to
Methods
experience delayed N&V. Delayed nausea also is more com-
mon in females, patients who drink little or no alcohol, and
Design
young patients. Seventy-five percent of those who do not ex-
perience N&V in the first 24 hours will not develop delayed
The design for this multisite research was a longitudinal,
N&V. However, this means that 25% of patients will develop
descriptive study during two cycles of chemotherapy. Usually
delayed N&V despite having no acute symptoms (Italian
a cycle of chemotherapy for women with breast cancer ranges
Group for Antiemetic Research, 2000).
from 2128 days.
Treating acute N&V is therefore an important component in
Sample and Setting
preventing delayed N&V. Chemotherapy induces acute N&V
through direct or indirect stimulation of the chemoreceptor trig-
The settings for this study consisted of 40 sites throughout
ger zone (CTZ) and vomiting center. The CTZ is located
the United States, including 7 outpatient oncology clinics situ-
postrema, on the surface of the brain on the floor of the fourth
ated in hospitals, 5 outpatient oncology clinics associated with
ventricle. It is located outside of the blood-brain barrier and can
major universities, 27 private outpatient oncology practices,
be stimulated directly by cytotoxic agents in the blood stream
and 1 outpatient clinic located in a county hospital. The sites
or cerebrospinal fluid (Pendergrass, 1998). The CTZ stimulates
were located in the western, eastern, and midwestern United
the vomiting center, which is located in the lateral reticular for-
States. The sites were a combination of urban and rural. Eli-
mation of the medulla oblongata, through key receptors: sero-
gibility criteria included (a) having a confirmed diagnosis of
tonin (5-HT3), dopamine (D2), and neurokinin (N1) (Oettle &
breast cancer, (b) being female, (c) receiving any nausea-in-
Reiss, 2001). The CTZ also can be stimulated by enterochroma-
ducing chemotherapy regimen, (d) being able to communicate
ffin cells on the gastrointestinal mucosa, which release 5-HT3
(both verbally and in writing) in English, and (e) being will-
when assaulted by cytotoxic agents. The 5-HT3 binds to 5-HT3
ing to participate in the study. Of the 353 eligible women who
receptors along the gastrointestinal tract, vagus nerve, and, ul-
were approached to participate, 50 women refused. The most
timately, the CTZ, which then sends a signal to the vomiting
common reason for refusal to participate was that patients
center (Dicato, 1996; NCCN, 2001). The stimulation of entero-
complained of feeling overwhelmed.
chromaffin cells and resultant release of serotonin largely is
Instruments
responsible for acute chemotherapy-induced N&V (Maisano et
al., 2000). The understanding of this chain of events and role of
The Patient Information Questionnaire (PIQ) was used
neurotransmitters in inducing N&V is an important element of
to collect demographic information, including age, education,
choosing the appropriate treatment regimen.
partnership status, ethnicity, employment status, and income.
The most effective medications used to treat chemotherapy-
This tool has been used successfully to collect demographic
induced acute N&V are aimed at blocking neurotransmitters that
data in previous studies.
ultimately stimulate the vomiting center. These medications
The Disease and Treatment Questionnaire (DTQ) docu-
include 5-HT3 antagonists (e.g., ondansetron, granisetron,
mented information from patients' medical records, including
tropisetron) and dopamine receptor antagonists (e.g., meto-
diagnosis date, surgical treatment, type of breast cancer, treat-
clopramide, alizapride) and are most effective when given prior
ment regimens, chemotherapy dosages, and antiemetics or-
to initiation of treatment. They can be used alone or in combi-
dered for IV chemotherapy and home use. Developed by the
nation with a corticosteroid such as dexamethasone, although
principal investigator of the current study, versions of this tool
the mechanism of action is not clearly understood (Oettle &
have been used for more than 15 years.
Reiss, 2001; Pendergrass, 1998). The combination of a 5-HT3
The daily log consisted of the three-item nausea experience
receptor antagonist and a corticosteroid is considered to be the
subscale from the Rhodes Index of Nausea, Vomiting, and
"gold standard" in treating moderately to highly emetogenic
Retching (INVR). These items measured the amount of time (in
doses of cyclophosphamide (Clavel, Soukop, & Greenstreet,
hours) that women experienced nausea, the distress that the
1993; Oettle & Riess; Stewart, 1996). A neuroleptic or
nausea produced, and the number of times per day nausea oc-
benzodiazapine may be used as rescue therapy. Delayed N&V
curred. This scale has established reliability and validity
may be reduced somewhat with the use of dexamethasone with
(Rhodes, Watson, & Johnson, 1984; Rhodes, Watson, Johnson,
DIBBLE VOL 30, NO 2, 2003
41
Madsen, & Beck, 1987). Items from this subscale were
2.9), and 56% had more than a high school education. The
summed. The subscale score could range from 012, with a
average body mass index (BMI, a ratio of weight to height) for
these women was 28.3 kg/m2 (SD = 6.1 kg/m2); 30% of the
higher number reflecting a more severe nausea experience. In
addition, the log provided a place for patients to record any
women had a BMI between 2530, which reflects being over-
interventions they used for N&V control. Ratings were en-
weight, and 35% of the women had a BMI of greater than 30,
tered on a daily basis prior to bedtime.
which indicates obesity. Most (68%) of the women had expe-
rienced morning sickness with a pregnancy, 24% had a history
Procedures
of seasickness, 20% had a history of being carsick, and 22%
Institutional review board approval of the protocol was ob-
had a history of nausea with stress (see Table 1).
tained for each institution participating in this study. Nurses at
each site participated in training about the conduct of the study
Table 1. Demographic Characteristics of Participants
either in person or via telephone. The training was conducted
by the project director, who did not release data packets to the
Characteristic
n
%
sites until this training was successfully completed. Research
Age (years)
assistants in the waiting room, physicians, or nurses approached
--
X (SD) = 51.9 (11.0)
potential participants about the study. After consenting to take
Range = 2886
part in the study, participants completed the baseline data col-
Education (years)
lection and were taught how to complete the daily logs. All
--
X (SD) = 13.9 (2.9)
women received their usual antiemetics as prescribed by their
Range = 723
physicians and recorded their usage on a daily basis. Partici-
Body mass index (kg/m2)
--
pants recorded in their daily logs for two cycles of chemo-
X (SD) = 28.3 (6.1)
therapy. Women who were receiving chemotherapy on a
Range = 15.5 40.4
weekly basis were asked to complete their logs for three weeks
Ethnicity
239
79
Caucasian
per log. In addition, nurses reviewed patients' medical records
062
21
Other
to obtain information about their cancer diagnosis, antiemetic
Sexual orientation
prescriptions, and current, previous, and known future treatment
272
96
Heterosexual
modalities. The project director reviewed the completed data
012
04
Other
packets to ensure the integrity and completeness of the data. All
Employed
participants who completed the study were paid $10 to thank
145
48
Yes
them for their time, and all sites received $90 per completed
155
52
No
study patient to defray the costs of participating in the study.
Born a U.S. citizen
281
93
Yes
Data Analysis
022
07
No
Retired
The SPSS statistical software package version 11 (SPSS,
066
22
Yes
Inc., Chicago, IL) as well as SAS version 8.2 (SAS Institute
234
78
No
Inc., Cary, NC) were used for data analysis. Data were double
Disabled
entered into SPSS, and discrepancies between the files were
041
14
Yes
resolved to ensure accuracy of the data entered. Descriptive
259
86
No
statistics were generated related to sample characteristics and
Personal income
other variables of interest. Repeated measures analysis of vari-
106
42
< $20,000
ance was used to determine the change in nausea over time. In
079
32
$20,00039,999
this analysis strategy, participants serve as their own controls so
065
26
> $40,000
that the variability resulting from individual differences is
Relationship status
196
65
Married or partnered
eliminated from the error term (Dawson-Saunders & Trapp,
105
35
Other
1994). This analysis technique is quite robust with small sample
Living alone
sizes and statistical assumption violations. In addition, a de-
048
16
Yes
layed nausea scale (DNS) was created by summing the nausea
253
84
No
subscale of the INVR for days 211 after chemotherapy admin-
History of car sickness
istration. Scores on the DNS could range from 0120. Because
061
20
Yes
of the small sample size, researchers did not attempt to explore
240
80
No
differences resulting from setting or types of treatment. Other
History of seasickness
statistical tests utilized were t tests, paired t tests, chi-square,
Yes
071
24
McNemar's test, and analysis of variance.
No
220
76
History of nausea with stress
066
22
Yes
Results
233
78
No
History of morning sickness
Typical participants (N = 303) were 51.9 years old (SD =
181
68
Yes
11.0), Caucasian (79%), married or partnered (65%), not on
086
32
No
disability (86%), unemployed (52%), born U.S. citizens
(93%), heterosexual (96%), not living alone (84%), and had
N = 303
annual personal incomes of more than $20,000 (58%). The
Note. Because some data are missing for some variables, the n values may not
average education for these participants was 13.9 years (SD =
equal the total N.
ONF VOL 30, NO 2, 2003
42
The average time since diagnosis for these women was 79.2
Table 3. Participants' Chemotherapy Treatments
days (SD = 278.5). Included in these statistics were two
women who had recurrent disease. Excluding those two
Characteristic
%
n
women resulted in an average time since diagnosis for the
Chemotherapy regimen
sample of 57.8 days (SD = 56.11) or approximately two
Cyclophosphamide/doxorubicin
228
76
months. Participants typically had surgical biopsy (64%) to
Cyclophosphamide/methotrexate/fluorouracil
11
034
determine that they had infiltrating ductal breast cancer
Cyclophosphamide/doxorubicin/fluoruracil
02
005
(80%). Most (62%) of the women did not have a mastectomy.
Doxorubicin/cyclophosphamide/paclitaxel
007
02
Multiple lymph nodes were examined in 241 women (80%),
Other
09
028
and 12% of the women had a sentinel node biopsy. Positive
Weekly chemotherapy
nodes were reported in 46% of the participants. Radiation
Yes
023
07
No
93
277
therapy had been completed or concurrent with their chemo-
Dosage of cyclophosphamide (mg) (n = 273)
therapy in 7% of the sample, and 61% were planning to un-
--
X (SD) = 993.2 (267.7)
dergo radiation therapy after finishing their chemotherapy (see
Range = 901,888
Table 2).
Dosage of 5-fluorouracil (mg) (n = 41)
Most (76%) of the women were receiving CA as their che-
--
X (SD) = 920.6 (232.2)
motherapy regimen. The average dose of doxorubicin was 103
Range = 601,200
mg, and the average dose of cyclophosphamide was 993 mg.
Dosage of doxorubicin (mg) (n = 258)
--
The dosages of chemotherapy were reduced between the two
X (SD) = 102.7 (16.9)
cycles of the study only 5% of the time. The most common IV
Range = 30145
antiemetics given during the administration of chemotherapy
Dosage of chemotherapy decreased with next cycle
05
Yes
014
were dexamethasone (80%), ondansetron (49%), granisetron
95
No
285
(24%), and tropisetron (17%). The types of IV antiemetics
IV antiemetics given
were changed between the two cycles of the study only 6% of
80
Dexamethasone
241
the time. The most common antiemetic ordered for home use
49
Ondansetron
148
was prochlorperazine (70%). The types of oral antiemetics or-
Granisetron
072
24
17
Tropisetron
051
07
Lorazepam
020
Table 2. Participants' Diagnostics and Surgical Treatments
04
Prochlorperazine
012
02
Diphenhydramine
007
%
Characteristic
n
IV antiemetics changed with subsequent
chemotherapy
Time since diagnosisa (months)
--
06
Yes
018
X (SD) = 1.93 (1.87)
94
282
No
Range = 0.0719.4
Oral antiemetics ordered
Surgical biopsy
70
Prochlorperazine
211
64
Yes
193
38
113
Ondansetron
No
36
108
068
23
Dexamethasone
Lumpectomy
20
059
Lorazepam
48
Yes
145
12
Granisetron
036
No
156
52
05
015
Phenergan
Mastectomy
015
05
Diphenhydramine
38
Yes
113
Oral antiemetics changed with subsequent
62
No
188
chemotherapy
Lymph node dissection
024
08
Yes
Yes
80
241
No
273
92
No
060
20
Sentinel node biopsy
N = 303
12
Yes
037
No
264
88
Note. Because some data are missing for some variables and some patients
Positive nodes
received more than one antiemetic treatment, the n values may not equal the
46
Yes
123
total N and percentages may not total 100.
142
54
No
Type of breast cancer
80
Infiltrating ductal
238
dered for home use were changed between the two cycles of
025
08
Infiltrating lobular
the study only 8% of the time (see Table 3).
Other
024
12
The pattern of delayed nausea as measured by the nausea
Radiation therapy
subscale of the INVR can be observed in Figure 1. The worst
019
07
Yes
nausea occurred on the third day after having chemotherapy
No
092
33
for breast cancer. Included in those statistics were those who
61
Planned after chemotherapy
171
did not experience nausea on a particular day. Figure 2 details
the percentage of participants who described any nausea as
N = 303
measured by the nausea subscale of the INVR on a particular
a
Excludes two patients who had recurrence.
day. More than half of the participants experienced nausea
Note. Because some data are missing for some variables, the n values may not
during both cycles of chemotherapy on days two, three, and
equal the total N. Because of rounding, percentages may not total 100.
DIBBLE VOL 30, NO 2, 2003
43
4
6
3.5
5.5
3
5
2.5
4.5
2
4
1.5
3.5
1
3
0.5
2.5
0
2
2
3
4
5
6
7
8
9
10
11
1.5
Days After Chemotherapy
1
Time 1
Time 2
0.5
0
Figure 1. Delayed Nausea Over Time
2
3
4
5
6
7
8
9
10
11
N = 253
Days After Chemotherapy
Time 1
Time 2
four. If the women who did not experience nausea on a par-
ticular day are eliminated from the analyses, nausea clearly is
Figure 3. Intensity of Delayed Nausea Over Time
a significant problem for those who have it (see Figure 3).
Note. Only patients who reported experiencing nausea are included.
The mean DNS score for the women during the first data
collection period was 17.1 (SD = 16.9, range = 0101, n =
265), and the mean DNS for the women during the second
period, 12 (27%) developed delayed nausea during their next
data collection period was 18.0 (SD = 20.6, range = 0111,
cycle of chemotherapy. Of the 198 women with delayed nau-
n = 252). These values were compared using a paired t test,
sea at the first data collection period, 35 (18%) did not expe-
and no significant differences existed in delayed nausea be-
rience delayed nausea with their next cycle.
tween the two time periods (t = 0.616, p = 0.539, n = 242). In
exploring the percentage of women who experienced abso-
Next, the researchers explored information about the
women who experienced the most intense delayed nausea,
lutely no delayed nausea, 18% of women during the first data
defined as those with a DNS score of 30 or greater. At time
collection period and 27% of the women during the second
were found to be free from delayed nausea. Using McNemar's
one, this represented 18% of the sample and increased to 23%
of the sample at time two. Demographic factors associated
test, researchers found significant (p = 0.001) differences in
the percent of women with delayed nausea from the first to
with a higher DNS score at time one included age (r = 0.21,
second data collection periods. Most (67%) experienced de-
p = 0.001) and weight (r = 0.17, p = 0.005); younger, heavier
women experienced more delayed nausea. These significant
layed nausea during both time periods, but 14% had no de-
relationships did not continue during the second time period.
layed nausea during both time periods (n = 243). Of the 45
women without delayed nausea at the first data collection
Education was not associated with DNS score at either time
period. No significant differences existed in DNS scores by
ethnicity, relationship status, or living circumstance. Signifi-
cant differences did exist in DNS scores by history of nausea
70
with stress; those who had nausea with stress had more severe
60
delayed nausea during both time periods (see Table 4). Al-
though the DNS scores were higher for those with a history of
50
seasickness, car sickness, or morning sickness, these differ-
40
ences during either time period were not significant. Those
receiving their chemotherapy on a weekly basis reported expe-
30
riencing less delayed nausea during the second time period than
20
those on a more traditional 21- or 28-day cycle. Women who re-
10
ceived IV ondansetron with their chemotherapy had higher
DNS scores during both time periods; however, the scores dur-
0
2
3
4
5
6
7
8
9
10
11
ing the second time period were significantly higher (p = 0.03).
Differences in DNS scores were not significant by any other IV
Days After Chemotherapy
antiemetic usage. Those who had their IV antiemetic changed
Time 1
Time 2
had significantly higher DNS scores during the first time period
(p = 0.034) but not during the second (p = 0.596).
Figure 2. Percentage of Sample With Delayed Nausea Over
Women who received oral prochlorperazine for home use
Time
had significantly lower DNS scores than those who did not
during the first time period (p = 0.023) but not during the
N = 253
ONF VOL 30, NO 2, 2003
44
Table 4. Comparison of Differences in Delayed Nausea by Various Factors
Time 1 (N = 265)
Time 2 (N = 252)
--
--
n
SD
p
n
SD
p
Variable
X
X
059
17.0
0.397
057
23.4
0.653
Reported history of car sickness
18.7
19.1
205
16.9
194
19.8
No history of car sickness
16.6
17.7
069
15.9
0.350
062
21.1
0.554
Reported history of seasickness
18.9
19.4
194
17.3
188
20.5
No history of seasickness
16.5
17.6
057
18.0
0.029
055
25.4
0.037
Reported history of nausea with stress
21.4
24.1
207
16.4
196
18.8
No history of nausea with stress
15.9
16.3
151
16.6
0.397
146
20.7
0.653
Reported history of morning sickness
18.4
19.6
113
17.2
105
20.4
No history of morning sickness
15.2
15.8
023
13.8
0.144
022
12.9
0.004
Receiving weekly chemotherapy
12.1
09.3
239
17.2
228
21.0
Not receiving weekly chemotherapy
17.5
18.9
128
17.9
0.317
123
22.2
0.030
Receiving IV ondansetron
18.2
21.0
134
15.9
127
18.7
Not receiving IV ondansetron
16.1
15.3
211
17.0
0.974
202
21.4
0.350
Receiving IV dexamethasone
17.1
18.7
052
16.9
048
17.1
Not receiving IV dexamethasone
17.0
15.6
019
14.9
0.640
017
18.2
0.092
Receiving IV lorazepam
18.8
26.2
244
17.1
233
20.7
Not receiving IV lorazepam
17.0
17.5
006
07.8
0.095
007
20.5
0.397
Receiving IV diphenhydramine
05.7
11.6
257
17.0
243
20.6
Not receiving IV diphenhydramine
17.0
18.3
063
15.5
0.692
060
20.2
0.844
Receiving IV granisetron
16.3
17.6
200
17.4
190
20.8
Not receiving IV granisetron
17.3
18.2
044
17.5
0.955
046
18.5
0.168
Receiving IV tropisetron
17.0
14.3
219
16.9
204
21.0
Not receiving IV tropisetron
17.1
18.9
015
15.1
0.034
016
19.1
0.596
Changed IV antiemetic
26.1
20.6
247
16.9
233
20.7
Did not change IV antiemetic
16.5
17.8
190
16.0
0.023
179
19.2
0.169
Receiving oral prochlorperazine
15.6
16.7
072
18.8
070
23.7
Not receiving oral prochlorperazine
20.9
21.1
052
15.1
0.262
048
16.6
0.797
Receiving oral lorazepam
19.4
17.3
210
17.4
201
21.5
Not receiving oral lorazepam
16.5
18.1
012
20.4
0.473
012
17.9
0.253
Receiving oral phenergan
20.5
11.3
250
16.8
237
20.7
Not receiving oral phenergan
16.9
18.3
013
18.7
0.818
013
18.9
0.546
Receiving oral dephenhydramine
16.0
14.6
249
16.9
236
20.7
Not receiving oral dephenhydramine
17.1
18.2
031
17.9
0.172
029
16.7
0.630
Receiving oral granisetron
21.0
16.2
231
16.8
220
21.1
Not receiving oral granisetron
16.5
18.2
098
17.3
0.234
099
20.1
0.048
Receiving oral ondansetron
18.7
21.1
164
16.7
150
20.5
Not receiving oral ondansetron
16.1
15.9
065
17.5
0.942
063
20.3
0.175
Receiving oral dexamethasone
17.0
14.9
Not receiving oral dexamethasone
197
16.8
186
20.7
17.1
19.0
Receiving cyclophosphamide
239
17.2
0.004
227
21.0
0.004
17.8
19.0
026
11.7
025
14.2
Not receiving cyclophosphamide
10.1
09.3
Receiving 5-fluorouracil
037
13.5
13.3
0.163
033
12.4
15.2
0.097
Not receiving 5-fluorouracil
228
17.7
17.3
219
18.8
21.2
Receiving doxorubicin
227
17.7
17.3
0.135
218
18.9
21.2
0.064
Not receiving doxorubicin
038
13.3
13.4
034
11.9
15.0
Chemotherapy regimen
Cyclophosphamide/doxorubicin
195
18.8
17.7
0.303
186
20.2
21.5
0.270
Cyclophosphamide/methotrexate/
031
15.4
15.9
028
15.5
18.8
5-fluorouracil
Note. Because some data are missing for some variables, the n values may not equal the total N.
DIBBLE VOL 30, NO 2, 2003
45
2001). A pilot study of Chinese patients with breast cancer us-
second (p = 0.169). Differences in DNS scores were not sig-
ing progressive muscle relation therapy demonstrated that this
nificant with any other oral antiemetic regimen except
therapy also is an effective adjuvant method to decrease nausea
ondansetron. Those women who received ondansetron dur-
(Molassiotis, Yung, Yam, Chan, & Mok, 2002). The results
ing the second time period had significantly higher delayed
from this study indicated that the usual historical nausea indi-
nausea scores (p = 0.048). Those who were taking cyclo-
cators (seasickness, car sickness, or morning sickness) were not
phosphamide had significantly higher DNS scores for both
associated with the delayed nausea experience. Therefore, on-
time periods (p = 0.004, p = 0.004). Although the DNS scores
cology nurses can tell patients that no association exists be-
were higher for patients receiving doxorubicin during both
tween delayed nausea and women's historical experiences,
time periods, no significant difference existed during either
except nausea under stress.
time period. Lastly, no statistically significant difference ex-
The relationship of BMI with delayed nausea is interesting.
isted in delayed nausea by chemotherapy regimen (CA/AC
Chemotherapy doses are determined by taking into account
versus CMF) during either time period.
body weight, yet antiemetics are not administered using those
guidelines. Another explanation might be that the clearance of
Discussion
chemotherapy from the bodies of women with higher BMI is
delayed, resulting in more delayed nausea. The relationship
The results of this study indicated that despite the emergence
between BMI and delayed nausea needs to be confirmed in a
of 5-HT3 antagonists (considered the "gold standard" for acute
future study. If a relationship is established, then the mecha-
chemotherapy-induced N&V), delayed nausea continues to be
nisms involved in delayed nausea need to be explored in fu-
a significant problem for patients with breast cancer. Of particu-
ture research efforts.
lar interest is the degree to which delayed nausea prevalence in-
Delayed nausea clearly is at its worst on the third day after
creases or persists despite treatment with multiple antiemetics,
chemotherapy administration. Perhaps a nursing intervention
potentially contributing to the withdrawal by patients of this
would be to call patients on this day to see how they are feel-
lifesaving treatment. This illustrates the need for better medica-
ing and whether they need to change their antiemetic medica-
tions or therapeutic techniques for patients to use while receiv-
tions, or to suggest other potentially useful interventions. Again,
ing chemotherapy for breast cancer. A myth exists that women
this project would need to be tested in a future research study.
no longer suffer from chemotherapy-related nausea. Time and
This study has a number of limitations. First, the sites that
again when the current study's researchers asked oncology
were used may have been those where nausea was a particular
practices to participate in nausea studies, they were told, "nau-
problem. The physicians who indicated that their patients did
sea is no longer a problem for our patients." The new medica-
not experience any nausea may have been right and this article
tions certainly have contributed to fewer women suffering from
is demonstrating the experience of those women who are not
these side effects in the office, but the current study's research
properly treated for this side effect. Second, participants in the
clearly demonstrates that a significant number of women con-
current study primarily were Caucasian, thus limiting the
tinue to suffer from delayed nausea despite these medications.
generalizability of this study to all racial and ethnic groups. For
Although healthcare professionals have come to a consensus on
instance, the researchers do not know if those with African
which medications to give for acute nausea, no such consensus
heritage experience delayed nausea differently than those of
exists for delayed nausea (Gandara et al., 1998; Gralla et al.,
Scandinavian heritage. Third, the women were not followed for
1999). Healthcare professionals still do not know the best phar-
their entire chemotherapy experience; thus, the researchers do
macologic or nonpharmacologic treatments to assist women
not know how many women eventually stopped treatment or if
who are suffering from chemotherapy-induced delayed nausea.
the nausea got better or worse with subsequent cycles.
The National Institutes of Health (NIH) Consensus Confer-
ence, which met in 1998 to evaluate existing medical literature
Summary
and discuss the use and effectiveness of acupuncture in treating
various conditions, stated that acupuncture is a beneficial treat-
ment for chemotherapy-induced nausea (NIH Consensus Devel-
Oncology nurses must recognize that delayed nausea is an
opment Panel on Acupuncture, 1998). However, acupuncture
issue at some time for most (82%) women undergoing chemo-
requires the skill of a trained professional. An effective, alterna-
therapy for breast cancer. This study provides a detailed ex-
tive technique to deal with chemotherapy-induced delayed nau-
amination of the phenomenon of chemotherapy-induced de-
sea may be acupressure, which follows the same principles and
layed nausea in women being treated for breast cancer. Future
pressure points as acupuncture but differs in that it is the appli-
research should explore the relationship among delayed nau-
cation of finger pressure instead of inserting a needle. Women
sea, anxiety, stress, BMI, and age, as well as specific anti-
can be taught to perform this treatment for themselves.
emetic regimens. The current study demonstrates that new
From the current study's data, the researchers know that
medications or other treatments must be developed and tested
women who experience nausea in stressful situations have a
because delayed nausea continues to be a problem for women
significantly higher rate of delayed nausea. Perhaps relaxation
since the advent of the 5-HT3 antagonists.
training may be useful for these women. Relaxation training has
been shown to effectively help patients deal with the side effects
Author Contact: Suzanne L. Dibble, RN, DNSc, can be reached at
of chemotherapy treatment (Luebbert, Dahme, & Hasenbring,
sdibble@itsa.ucsf.edu, with copy to editor at rose_mary@earthlink.net.
References
American Cancer Society. (2003). Cancer facts and figures 2003. Atlanta,
emesis and quality of life with ondansetron in breast cancer. Oncology, 50,
GA: Author.
180185.
Clavel, M., Soukop, M., & Greenstreet, Y.L.A. (1993). Improved control of
Dawson-Saunders, B., & Trapp, R.G. (1994). Basic and clinical biostatistics.
ONF VOL 30, NO 2, 2003
46
Norwalk, CT: Appleton and Lange.
Oettle, H., & Riess, H. (2001). Treatment of chemotherapy-induced nausea
and vomiting. Journal of Cancer Research and Clinical Oncology, 127,
Dicato, M. (1996). Mechanisms and management of nausea and emesis. On-
cology, 53(Suppl. 1), 13.
340345.
Fessele, K.S. (1996). Managing the multiple causes of nausea and vomiting
Osoba, D., Zee, B., Warr, D., Latrelle, J., Kaizer, L., & Pater, J. (1997). Ef-
fect of postchemotherapy nausea and vomiting on health-related quality of
in the patient with cancer. Oncology Nursing Forum, 23, 14091415.
Gandara, D.R., Roila, F., Warr, D., Edelman, M.J., Perez, E.A., & Gralla, R.J.
life. Supportive Care in Cancer, 5, 307313.
(1998). Consensus proposal for 5HT3 antagonists in the prevention of acute
Pendergrass, K.B. (1998). Options in the treatment of chemotherapy-induced
emesis. Cancer Practice, 6, 276281.
emesis related to highly emetogenic chemotherapy. Dose, schedule, and
route of administration. Supportive Care in Cancer, 6, 237243.
Rhodes, V.A., & McDaniel, R.W. (1997). Measuring nausea, vomiting and
Goodman, M. (1997). Risk factors and antiemetic management of chemo-
retching. In M. Frank-Stromborg & S.J. Olsen (Eds.), Instruments for clini-
cal health-care research (2nd ed., pp. 509518). Boston: Jones and
therapy-induced nausea and vomiting. Oncology Nursing Forum, 24, 2032.
Gralla, R.J., Osoba, D., Kris, M.G., Kirkbride, P., Hesketh, P.J., Chinnery,
Bartlett.
L.W., et al. (1999). Recommendations for the use of antiemetics: Evi-
Rhodes, V.A., Watson, P.M., & Johnson, M.H. (1984). Development of re-
liable and valid measures of nausea and vomiting. Cancer Nursing, 7, 33
dence-based, clinical practice guidelines. Journal of Clinical Oncology, 17,
29712994.
41.
Rhodes, V.A., Watson, P.M., Johnson, M.H., Madsen, R.W., & Beck, N.C.
Greene, D., Nail, L.M., Fieler, V.K., Dudgeon, D., & Jones, L.S. (1994). A
(1987). Patterns of nausea, vomiting and distress in patients receiving an-
comparison of patient-reported side effects among three chemotherapy
regimens for breast cancer. Cancer Practice, 2, 5762.
tineoplastic drug protocols. Oncology Nursing Forum, 14, 3544.
Stewart, A. (1996). Optimal control of cyclophosphamide-induced emesis.
Italian Group for Antiemetic Research. (2000). Dexamethasone alone or in
Oncology, 53(Suppl. 1), 3238.
combination with ondansetron for the prevention of delayed nausea and
vomiting induced by chemotherapy. New England Journal of Medicine,
Uyl-de Groot, C.A., Wait, S., & Buijt, I. (2000). Economics and health-related
342, 15541559.
quality of life in antiemetic therapy: Recommendations for trial design.
European Journal of Cancer, 36, 15221535.
Luebbert, K., Dahme, B., & Hasenbring, M. (2001). The effectiveness of re-
laxation training in reducing treatment-related symptoms and improving
emotional adjustment in acute non-surgical cancer treatment: A meta-ana-
lytical review. Psychooncology, 10, 490502.
For more information . . .
Maisano, R., Spadaro, P., Toscano, G., Caristi, N., Pergolizzi, S., & Salimbeni,
V. (2000). Cisapride and dexamethasone in the prevention of delayed eme-
CancerSymptoms.org
sis after cisplatinum administration. Supportive Care in Cancer, 9, 6164.
www.cancersymptoms.org
Molassiotis, A., Yung, H.P., Yam, B.M., Chan, F.Y., & Mok, T.S. (2002).
CancerNausea.com
The effectiveness of progressive muscle relaxation training in managing
chemotherapy-induced nausea and vomiting in Chinese breast cancer pa-
www.cancernausea.com
tients: A randomized controlled trial. Supportive Care in Cancer, 10, 237
Chemotherapy-Induced Nausea and Vomiting Summary
246.
Monograph
National Comprehensive Care Network. (2001). Nausea and vomiting: Treat-
www.anzemet.com/cinv_sum.shtml
ment guidelines for patients with cancer. Atlanta, GA: American Cancer
Society and Author.
Links can be found using ONS Online at www.ons.org.
National Institutes of Health Consensus Development Panel on Acupuncture.
(1998). Acupuncture. JAMA, 280, 15181524.
DIBBLE VOL 30, NO 2, 2003
47