Health Psychology Copyright 1993 by the American Psychological Association, Inc.

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1993, Vol. 12, No. 6,469-475 the Division of Health Psychology/0278-6133/93/$3.00

Anticipatory Anxiety in Women Receiving Chemotherapy

for Breast Cancer
Paul B. Jacobsen, Dana H. Bovbjerg, and William H. Redd

This study examined (a) the prevalence and course of anxiety before the 1st 6 infusions of cancer
chemotherapy and (b) the contribution of trait anxiety, side effect expectations, and prior
occurrence of posttreatment side effects to anxiety before infusions. Fifty-three women receiving
adjuvant chemotherapy for breast cancer participated. Anxiety was most prevalent and intense
before the 1st infusion. Trait anxiety predicted anxiety before both the 1st and subsequent
infusions. Prior occurrence of posttreatment nervousness also predicted anxiety before subsequent
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infusions, even after accounting for trait anxiety and other posttreatment side effects. Results are
discussed in terms of the role that anxiety proneness, response expectancy, and classical
conditioning may play in the development of anxiety before repeated chemotherapy infusions.

Key words: anxiety, breast cancer, chemotherapy, classical conditioning

Heightened emotional distress in cancer patients undergo-
ing chemotherapy treatment has been well documented (Coons,
Leventhal, Nerenz, Love, & Larson, 1987; Hughson, Cooper,
McArdle, & Smith, 1986; Leventhal, Easterling, Coons, Luch-
terhand, & Love, 1986; Love, Leventhal, Easterling, & Nerenz,
1989; Maguire et al., 1980; Meyerowitz, Sparks, & Spears,
1979; Nerenz, Leventhal, & Love, 1982; Sabbioni, Bovbjerg,
Jacobsen, Manne, & Redd, 1992). The anxiety, depression,
and other manifestations of distress that many patients experi-
ence can have disruptive effects on daily life and can compli-
cate the delivery of medical care. Patients who are distressed
are more likely to consider prematurely terminating poten-
tially curative treatment (Love et al., 1989).
Previous longitudinal studies (Leventhal et al., 1986; Love et
al., 1989) have shown that the degree of distress patients
experience after chemotherapy infusions is related to the
occurrence of noxious posttreatment side effects (e.g., fatigue,
nausea, and vomiting). In addition to experiencing distress
after infusions, patients may experience distress in anticipation
of treatment (Sabbioni et al., 1992). That is, they may experi-
ence anxiety and distress in the minutes or hours preceding a
chemotherapy infusion. Despite its potential clinical and
theoretical significance, anticipatory anxiety related to chemo-
Paul B. Jacobsen, Dana H. Bovbjerg, and William H. Redd,
Psychiatry Service, Department of Neurology, Memorial Sloan-
Kettering Cancer Center, New York City.
This research was supported by National Institute of Mental Health
Grant 45157, National Cancer Institute Grant 58178, American
Cancer Society Junior Faculty Research Awards 424 (Paul B. Jacob-
sen) and 268 (Dana H. Bovbjerg), and National Institute of Mental
Health Research Scientist Award 882 (William H. Redd).
We wish to thank Marzio E. E. Sabbioni and Michael A. An-
drykowski for their contributions to the design of this study and
Thomas H. Hakes, Violante E. Currie, and Richard J. Kaufman for
their assistance in recruiting participants.
Correspondence concerning this article should be addressed to Paul
B. Jacobsen, Psychiatry Service, Memorial Sloan-Kettering Cancer
Center, 1275 York Avenue, New York, New York 10021.
therapy has yet to be systematically investigated. From a
clinical standpoint, anxiety before infusions is important be-
cause of the effects it may have on patients' quality of life and
adherence to treatment. From a theoretical standpoint, anxi-
ety before infusions is interesting because it provides an
opportunity to explore how different mechanisms may contrib-
ute to anticipatory anxiety in medical situations. In the case of
chemotherapy, an important distinction can be made between
anxiety experienced before the first infusion (i.e., before any
experience with posttreatment side effects) and anxiety experi-
enced before subsequent infusions (i.e., after actual experi-
ence of posttreatment side effects).
At least two mechanisms may explain the development of
anxiety in patients awaiting their first chemotherapy infusion.
One involves a proneness toward experiencing anxiety in
threatening situations (Spielberger, Gorsuch, & Lushene,
1970). Individual differences in trait anxiety have been shown
to predict anxiety responses to both laboratory stressors
(Bohnen, Nicolson, Sulon, & Jolles, 1991) and challenging life
events such as surgery (Auerbach, 1973; Fox, O'Boyle, Len-
non, & Keeling, 1989; Johnson, Dabbs, & Leventhal, 1970;
Spielberger, Auerbach, Wadsworth, Dunn, & Taulbee, 1973;
Wallace, 1987). This research suggests that patients who are
higher in trait anxiety are likely to be more anxious before their
first chemotherapy infusion.
Another means by which anxiety could arise before the first
infusion is through the development of response expectancies.
Expectations for what will happen in a given situation have
been shown to be a major determinant of subsequent reactions
(Kirsch, 1985). With regard to anticipatory anxiety, patients
who expect chemotherapy to result in more noxious side effects
may be more likely to experience anxiety before the first
infusion. The development of expectations may predate any
personal experience with chemotherapy because information
about posttreatment side effects is readily available to patients
from a variety of sources (e.g., other patients, medical person-
nel, and the mass media).
At subsequent infusions, the actual experience of posttreat-

469
 470 P. JACOBSEN, D. BOVBJERG, AND W. REDD
ment side effects may be an additional source of anticipatory
anxiety. Two mechanisms, operating alone or in combination,
can be identified. First, patients who experience side effects
after an infusion may become anxious before a subsequent
infusion on the basis of expectations of again experiencing
noxious physical symptoms. Second, the experience of posttreat-
ment side effects could contribute to the development of a
conditioned anxiety response. According to this view (Sabbioni
et al., 1992), patients may become anxious before subsequent
infusions when they are reexposed to clinic cues (conditioned
stimuli) previously paired with chemotherapy administration
(unconditioned stimulus) and the occurrence of posttreatment
nervousness (unconditioned response). Along these lines, we
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recently reported that levels of distress in the chemotherapy
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clinic before an infusion were significantly higher than levels
measured the previous day in patients' homes (Sabbioni et al.,
1992). The possibility that anxiety can be conditioned is
supported by an extensive experimental literature demonstrat-
ing the formation of conditioned emotional responses after
distinctive cues (conditioned stimuli) have been associated
with aversive events (e.g., electric shock as an unconditioned
stimulus; Hall, 1986). These conditioned responses resemble
anxiety in that the presentation of a conditioned stimulus can
elicit distress and fear behaviors (Rachman, 1991).
The present study had two major aims. The first was to
determine the prevalence and course of anticipatory anxiety
over repeated infusions of chemotherapy. The second was to
explore several mechanisms that could contribute to anxiety
before chemotherapy infusions. We hypothesized that trait
anxiety and expectations of posttreatment side effects would
be associated with anxiety before the first infusion. For
subsequent infusions, we theorized that experience of side
effects after chemotherapy administration would represent an
additional source of anticipatory anxiety; patients who experi-
enced noxious side effects were considered to be more likely to
have anticipatory anxiety at subsequent infusions. A contribu-
tion of posttreatment nervousness (putative unconditioned
response), above and beyond the contribution of other side
effects, would suggest that conditioning also plays a role in the
development of anticipatory anxiety. Data for this report were
collected as part of a larger investigation of factors associated
with the development of anticipatory nausea (Andrykowski et
al., 1988) and posttreatment nausea (Jacobsen et al., 1988) in
cancer chemotherapy patients.
Method
Patients
Participants were patients at a large comprehensive cancer center
who (a) were at least 18 years of age, (b) had undergone mastectomy
for breast carcinoma, (c) had histologic evidence of lymphatic invasion
(but no distant metastases), (d) had not previously received radio-
therapy or cytotoxic chemotherapy, (e) were scheduled to receive their
first six infusions of outpatient adjuvant chemotherapy according to a
standard treatment protocol (described later), and (f) consented to
participate in a prospective longitudinal study of chemotherapy side
effects. Of the 82 women asked to participate, 77 (94%) consented.
Results are reported for 53 women (Af age = 49 years; range = 29 to
78) who received their first six infusions according to the standard
treatment protocol and provided complete data. Six of the participants
were single, 34 were married, 4 were widowed, and 9 were divorced or
separated. The median level of education was 13 years (range = 7 to
18 years). Among the 77 patients consenting to participate, the 53
women who were included in the study did not differ from the 24
women who were excluded in terms of age, years of education, marital
status (married or not married), or chemotherapy dose schedule (high
or low;ps > .47).
Chemotherapy Treatment Protocol
As part of their adjuvant chemotherapy treatment, patients were
assigned to either a low-dose (n = 32) or high-dose (n = 21) chemo-
therapy schedule before entry into the current study. At the outset,
patients were randomly assigned to either schedule; however, because
of the increased incidence of hematologic suppression in the high-dose
arm, assignment to this schedule was discontinued midway through the
current study. The low-dose schedule consisted of weekly intravenous
(IV) infusions of vincristine (0.43 mg/m 2 ), methotrexate (15 mg/m 2 ),
and 5-fluorouracil (300 mg/m 2 ), as well as daily oral administration of
cyclophosphamide (60 mg/m 2 ) for a period of 52 weeks. The high-dose
schedule involved weekly IV infusions of vincristine (0.73 mg/m 2 ),
methotrexate (25 mg/m 2 ) and 5-fluorouracil (500 mg/m 2 ), in addition
to daily oral cyclophosphamide (100 mg/m 2 ). In the high-dose sched-
ule, six weekly chemotherapy infusions alternated with 4 weeks of no
treatment for a period of 1 year. Both the low-dose and high-dose
schedules included daily oral prednisone (10-20 mg/m2) during the
first 6 weeks of treatment and daily oral tamoxifen (40 mg) for 1 year
(for women with estrogen receptor positive tumors). At each infusion
after the first, the actual doses of chemotherapy agents were subject to
minor downward adjustments based on laboratory evidence of the
extent of hematologic suppression. Because preliminary analyses
indicated that dose schedule was not significantly (p < .05) related to
any of the outcome measures included in the present study, it was
dropped from further consideration. To maintain a uniform time
interval between infusions (1 week), the current study was limited to
the initial six chemotherapy treatments.
Procedure
Participants were recruited, provided informed consent, and com-
pleted a baseline assessment just before their first infusion in the clinic
waiting area. A preinfusion assessment was conducted in the waiting
area immediately before each chemotherapy infusion. A postinfusion
assessment was conducted by telephone approximately 24 hr after
each chemotherapy infusion. All interviews were conducted by a
female research assistant or a male psychologist.
Baseline assessment. Before their first infusion, participants com-
pleted the State-Trait Anxiety Inventory trait form; (Spielberger et al.,
1970), a self-report measure of anxiety proneness. The internal
consistency of responses to this 20-item scale was high (a = .91).
Participants also completed a self-report measure assessing expecta-
tions about the development of 11 commonly reported side effects of
chemotherapy (described later; Cassileth et al., 1985). For each
symptom, expectation ratings were made on separate 5-point scales
ranging from certain I will not have this (1) to certain I will have this (5).
These ratings were then summed to yield an overall score. The internal
consistency of responses to the 11-item expectation measure was high
(« = .92).
Preinfusion assessment. Anxiety was measured on a 100-mm visual
analog scale (VAS) ranging from no anxiety (0) to anxiety as bad as it
could be (100; Andrykowski, Redd, & Hatfield, 1985). Ratings were
obtained in the clinic just before each chemotherapy infusion for the
following time points: previous evening, morning while at home, on
arriving at the clinic, and immediately before the infusion (current).
 ANTICIPATORY ANXIETY DURING CANCER CHEMOTHERAPY 471

Table 1 Table 2
Anticipatory Anxiety and Posttreatment Side Effects Across the Multiple Regression Analysis of Anticipatory Anxiety Intensity
Course of Treatment at Infusion 1
Anticipatory anxiety Variable r P R2 change
Prevalence Intensity No. side effects3 Trait anxiety .38** .38 .14**
Age -.28* -.29 .08*
Infusion n % M SD M SD Side effect expectations .08 .08 .01
1 48 91 37.23 29.75 1.85 2.11 Note. Multiple R = .48, F(3,49) = 4.82,p = .005.
2 34 64 19.82 25.03 2.04 1.94 *p < .05. **p < .01.
3 32 60 17.11 23.39 2.02 1.71
4 32 60 15.58 22.48 2.53 2.24
5 28 53 15.00 24.51 2.70 1.88
6 30 57 14.27 19.76 2.55 2.23 than nervousness across the six infusions, F(5,230) = 4.05,p =
.002. A post hoc comparison of the first and sixth infusions
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Note. N = 53.
revealed that the average number of side effects other than
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a
Excluding posttreatment nervousness.
Patients were classified as having anticipatory anxiety if they reported
anxiety intensity greater than zero on any of the four preinfusion VAS
measures (previous evening, morning, arrival at clinic, or immediately
before the infusion). Reliability analysis indicated that there was a
high degree of internal consistency among the four anticipatory
anxiety scores from each infusion (alphas ranging from .89 to .96).
Consequently, the four VAS scores from each infusion were averaged
to yield a single measure of the intensity of anticipatory anxiety.
Postinfusion assessment. During the postinfusion assessment, pa-
tients were asked whether they had experienced any of the following
11 commonly reported side effects in the 24 hr after chemotherapy
administration: nausea, vomiting, change in taste or appetite, feeling
tired, hair loss, skin itching, pain, weakness, diarrhea, chills, and
nervousness. This information was used to measure (a) the occurrence
of nervousness after each infusion and (b) the number of side effects
other than nervousness that occurred after each infusion. The internal
consistency (alpha) of the 10-symptom measure that excluded nervous-
ness ranged from .56 to .76 across the six infusions that were studied
(M = .69).
Results
Anticipatory Anxiety Across Infusions
As shown in Table 1, the prevalence of anticipatory anxiety
declined by 27% between Infusions 1 and 2 (binomial test,
p = .001) and remained lower across subsequent infusions.
The intensity of anticipatory anxiety also declined between the
first and second infusions, F(l, 52) = 24.51, p < .001, and
remained lower across subsequent infusions (see Table 1). The
number of times patients reported anxiety before an infusion
ranged from zero (« = 2) to six (n = 14), with a median of four
episodes per patient.
Posttreatment Side Effects Across Infusions
The prevalence of posttreatment nervousness after each
infusion was fairly constant, ranging from a low of 26%
(Infusion 1) to a high of 34% (Infusions 3 and 4). The number
of times patients reported nervousness after an infusion
ranged from zero (n = 20) to six (n = 1), with a median of one
episode per patient. The number of side effects other than
nervousness reported after each infusion is listed in Table 1.
Repeated measures analysis of variance indicated that there
were significant changes in the frequency of side effects other
nervousness increased significantly over the course of treat-
ment, F(l, 46) = 4.89, p = .03.
Factors Associated with Anticipatory Anxiety at Infusions
1,2, and 6
Anxiety before Infusion 1. Patients' age and scores on the
baseline measures (trait anxiety and side effect expectations)
were examined for their associations with anxiety intensity
before the first infusion. As shown in Table 2, more intense
anxiety before Infusion 1 was associated with higher levels of
trait anxiety and younger age; side effect expectations were not
related to anxiety intensity before Infusion 1. A multiple
regression analysis was performed to examine the amount of
variability in anxiety intensity before the first infusion ac-
counted for by each variable. Trait anxiety and age both
emerged as significant (p < .05) predictors of anxiety before
Infusion 1 and together accounted for 22% of the variance (see
Table 2). Because of the high percentage of patients who were
anxious before the first infusion (91%), an analysis comparing
patients with and without anxiety could not be conducted.
Anxiety before Infusion 2. In the next set of analyses,
patients who reported anxiety before Infusion 2 (n = 34) were
compared with patients who did not report anxiety (n = 19).
The following variables were examined for their associations
with the presence of anxiety before Infusion 2: age, the
baseline measures of trait anxiety and side effect expectations,
anxiety before Infusion 1 (i.e., previous level of anticipatory
anxiety), nervousness after Infusion 1, and the number of side
effects other than nervousness after Infusion 1. As shown in
Table 3, anxiety was more likely to be present before Infusion 2
Table 3
Correlational Analysis of Anticipatory Anxiety at Infusion 2
Variable r
Age -.06
Trait anxiety .28*
Side effect expectations .09
Anxiety3 before Infusion 1 .27*
Nervousness after Infusion 1 .38*
No. of side effects after Infusion l b .34*
Note. N = 53.
a b
As measured by visual analog scale. Excluding nervousness after
Infusion 1.
"p < .05. "*p < .01.
 472 P. JACOBSEN, D. BOVBJERG, AND W. REDD
Table 4
Logistic Regression Analysis of Anticipatory Anxiety at Infusion 2
Step /variable X2 improvement
Stepl 5.22
Trait anxiety
Anxiety8 before Infusion 1
Step 2 3.39
No. side effects after Infusion l b
Step 3 5.46
Nervousness after Infusion 1
b As measured by visual analog scale.
"As measured by visual analog scale. Excluding nervousness after
Infusion 1.
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in patients who reported higher trait anxiety and more anxiety
before Infusion 1. In addition, patients who experienced
nervousness and who experienced a greater number of side
effects other than nervousness after Infusion 1 were more
likely to be anxious before Infusion 2. A multiple logistic
regression analysis was conducted to examine the specific
contribution of posttreatment nervousness to anxiety before
Infusion 2 (see Table 4). In this analysis, trait anxiety and
anxiety intensity before Infusion 1 were entered into the model
in the first step, the number of posttreatment side effects other
than nervousness was entered in the second step, and occur-
rence of posttreatment nervousness was entered in the third
and final step. After the predictive value of the other variables
in the first two steps was controlled, the occurrence of
nervousness after Infusion 1 significantly improved the ability
of the model to predict anxiety before Infusion 2 (see Table 4).
Anxiety before subsequent infusions. To confirm the contribu-
tion of posttreatment nervousness to subsequent anticipatory
anxiety, the occurrence of anxiety before the sixth (final)
infusion was also examined by means of multiple logistic
regression (see Table 5). As in the previous analysis, trait
anxiety and anxiety intensity before Infusion 1 were entered
into the model in the first step. Prior experience of side effects
other than nervousness was entered in the second step by
tabulating the number of times patients reported the other
symptoms across Infusions 1 through 5. Prior experience of
posttreatment nervousness (number of occurrences across
Infusions 1 through 5) was entered into the model in the third
and final step. After controlling for the predictive value of the
other variables in the first two steps, the number of prior
occurrences of nervousness significantly improved the ability
of the model to predict anxiety before Infusion 6 (see Table 5).
Table 5
Logistic Regression Analysis of Anticipatory Anxiety at Infusion 6
Step/variable X2 improvement
Step 1 12.59
Trait anxiety
Anxiety3 before Infusion 1
Step 2 1.42
No. side effects after Infusion 1-5"
Step 3 6.43
Nervousness after Infusions 1-5
"As measured by visual analog scale.
b
Excluding nervousness after
Infusions 1-5.
Table 6
Multiple Regression Analysis of the Frequency of Anticipatory
Anxiety Episodes Across Infusions 3 to 6
P
.07 Variable r P R2 change
Trait anxiety .46** .46 .21**
Anxiety" before Infusion 1 .36* .22 .04
.07 Nervousness after Infusion 1 .26 .17 .03
Anxiety before Infusion 2 .50** .36 .10*
.02
Note. Multiple R = .61, F(4,48) = 7.42, ;> = .0001.
a
"p < .01. **p < .001.
Factors Associated With the Number of Episodes of
Anticipatory Anxiety
Prevalence data presented earlier indicated that similar
numbers of patients reported anxiety before the second
through the sixth infusions. This finding raises the question of
whether the same individuals who reported anxiety before
Infusion 2 continued to report anxiety before subsequent
infusions. To examine this issue, the correlation between
anxiety before Infusion 2 and the number of episodes of
anticipatory anxiety across Infusions 3 through 6 was com-
puted. Three variables previously found to be related to
anxiety before Infusion 2 (trait anxiety, anxiety intensity before
Infusion 1, and occurrence of nervousness after Infusion 1)
were also examined for their relation to the number of
episodes of anticipatory anxiety. Findings showed that more
episodes of anticipatory anxiety were reported between Infu-
sions 3 and 6 by patients who were anxious before the second
infusion (M = 2.79) than by patients who were not anxious
before the second infusion (M - 1.16; see Table 6). Higher
levels of trait anxiety and more intense anxiety before the first
infusion were also related to more episodes of anticipatory
anxiety.
To examine the specific contribution of anxiety before the
second infusion, a hierarchical multiple regression analysis was
conducted with the number of episodes of anticipatory anxiety
(Infusions 3 through 6) as the dependent variable (see Table
6). After accounting for variability attributable to trait anxiety,
anxiety before Infusion 1, and nervousness after Infusion 1, the
occurrence of anxiety before Infusion 2 still explained signifi-
cant variability in the number of subsequent episodes of
anticipatory anxiety (see Table 6).
Discussion
In this study, we sought to distinguish anxiety experienced
before an initial chemotherapy infusion from anxiety experi-
enced before subsequent infusions. The results indicated that
P this was a useful distinction. More patients were anxious
.002 before the first infusion than before other infusions, and
anxiety was more intense before the first infusion than before
other infusions. Moreover, the factors associated with anxiety
.23
before the first infusion differed from those associated with
.01 anxiety before subsequent infusions. The discussion to follow
summarizes what was learned about the factors contributing to
anticipatory anxiety at the first and subsequent chemotherapy
infusions; examines the role of anxiety proneness, response
 ANTICIPATORY ANXIETY DURING CANCER CHEMOTHERAPY
expectancies, and treatment side effects in the development of
anxiety before infusions; and considers the clinical implica-
tions of the research.
As expected, trait anxiety was associated with anticipatory
anxiety at both the first infusion and the second infusion. Thus,
trait anxiety contributes to anticipatory anxiety before patients
have ever experienced treatment side effects (i.e., before the
first infusion) as well as after they have experienced treatment
side effects (i.e., before the second infusion). These findings
parallel those from studies of patients undergoing elective
surgical procedures. In these studies (Auerbach, 1973; Spiel-
berger et al., 1973; Taenzer, Melzack, & Jeans, 1986), higher
levels of trait anxiety were found to be associated with higher
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levels of state anxiety measured before as well as after surgery.
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Research on chemotherapy and surgical patients suggests that
trait anxiety reflects an individual's proneness toward experi-
encing anxiety in both the presence and absence of any direct
personal experience with a medical stressor.
The hypothesis that expectations of treatment side effects
would be associated with anxiety before infusions was not
supported. One reason the relationship may not have been
evident was that most patients had high expectations of
experiencing side effects. Only 2 of the 53 patients (4%) were
certain they would have none of the 11 side effects assessed; in
contrast, 35 patients (66%) indicated that it was possible they
would experience all 11 side effects.
An unanticipated finding was that anxiety before the first
infusion was more intense in younger patients. Although not
expected, this finding is consistent with previous reports that
younger women experience more distress after the diagnosis of
breast cancer (Jamison, Wellisch, & Pasnau, 1978; Metzger,
Rogers, & Bauman, 1983; Northouse & Swain, 1987). The
mechanisms underlying the relationship between age and
anxiety before the first infusion have yet to be determined.
One possibility is that younger women may perceive them-
selves as more vulnerable to the potentially disruptive effects
of chemotherapy treatment on major areas of life functioning
(e.g., occupational, social, sexual, and reproductive function-
ing)-
The hypothesis that previous experience of treatment side
effects would be related to anxiety before subsequent infusions
was confirmed by study results. Patients who experienced more
side effects after the first infusion were more likely to report
anxiety before the second infusion. Among the various side
effects, results pointed to the special role of posttreatment
nervousness in the development of anxiety before subsequent
infusions. After accounting for the combined predictive value
of other side effects and trait anxiety, the prior occurrence of
posttreatment nervousness still predicted the occurrence of
anxiety before infusions. The associations found between
nervousness after infusions and anxiety before subsequent
infusions suggest three possibilities.
One possibility is that the relation between posttreatment
nervousness and subsequent anticipatory anxiety reflects the
presence of continued distress throughout the interval be-
tween infusions. This possibility seems unlikely because acute
treatment side effects routinely abated during the interval
between infusions. A second possibility is that patients who
experienced posttreatment nervousness, along with other side
473
effects, developed expectations that further treatment would
again result in noxious side effects. When these patients
returned for their second infusion, expectations of reexperienc-
ing side effects may have produced anticipatory anxiety.
Unfortunately, the design of the present study did not allow us
to test this mechanism because side effect expectations were
assessed only before the first infusion (i.e., before patients had
ever experienced side effects).
A third possible explanation for the results is that the
occurrence of posttreatment nervousness contributed to the
development of a conditioned anxiety response. That is,
patients who had previously experienced posttreatment ner-
vousness (unconditioned response) became anxious before
subsequent infusions (conditioned response) when they were
reexposed to cues (conditioned stimuli) previously paired with
chemotherapy administration (unconditioned stimulus). It
should be noted that the presence of anxiety before subse-
quent infusions was not attributable solely to the co-
occurrence of anticipatory nausea and anticipatory anxiety.
Only 7% of patients on this regimen experienced nausea
before the second infusion (Andrykowski et al., 1988), whereas
64% of patients in the present study experienced anxiety
before the second infusion.
Additional support for the role of conditioning in the
development of anticipatory anxiety would require a research
design in which the putative conditioned stimuli are presented
in the absence of any expectations on the patients' part of
receiving chemotherapy. For example, anxiety could be mea-
sured during a visit to the chemotherapy clinic after the
completion of all scheduled treatment. A clinical study that
incorporated some of these design features was conducted by
Cella, Pratt, and Holland (1986). Patients who had completed
chemotherapy treatment at least 6 months earlier were asked
whether any reminders of treatment elicited anxiety. Eighty
percent of the sample reported that stimuli associated with
treatment (e.g., sight of the chemotherapy clinic) caused them
to feel anxious.
Although results from the present study are consistent with
a conditioning explanation, other psychological mechanisms
could also account for the observed pattern of results. We have
already pointed out that anxiety before subsequent infusions
could be a reflection of patients' expectations of again experi-
encing treatment side effects. Another mechanism that may
underlie the observed results is the effect of coping processes
on emotional distress. Research has shown that patients who
use certain forms of coping (e.g., escape-avoidance) in dealing
with the diagnosis and treatment of cancer report greater
emotional distress (Dunkel-Schetter, Feinstein, Taylor, &
Falke, 1992; Felton, Revenson, & Hinrichsen, 1984; Weisman
& Worden, 1976-1977). These findings raise the possibility
that the relation between posttreatment nervousness and
anticipatory anxiety is due to the use of specific coping
processes across the course of chemotherapy treatment.
The results of the present study have several implications for
clinical practice. First, the high prevalence and intensity of
anxiety before the first infusion suggest that patients about to
begin chemotherapy could benefit from some form of psycho-
logical preparation. Anxiety before the start of chemotherapy
treatment may be due, in part, to factors that are remediable
 474 P. JACOBSEN, D. BOVBJERG, AND W. REDD
(e.g., unfamiliarity with chemotherapy administration proce-
dures and lack of accurate information about side effects). A
second implication is that routine assessment of patients early
in the course of chemotherapy treatment may be useful in
identifying patients who are likely to experience anxiety before
infusions. The results of this study showed that patients who
would repeatedly experience anticipatory anxiety could be
identified prospectively by their levels of trait anxiety and by
the presence of anxiety before the second infusion. A third
implication is that greater attention should be devoted to the
assessment of anticipatory anxiety during the course of chemo-
therapy treatment. Although many patients experienced little
or no anxiety before infusions, several repeatedly experienced
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severe anxiety before infusions. Through careful assessment, it
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may be possible to identify medical or psychological factors
that predispose certain individuals to become highly anxious
before chemotherapy administrations. The fourth and final
implication is that effective methods for reducing anxiety
before chemotherapy infusions should be identified. Several
cognitive-behavioral interventions have been developed and
shown to be effective with chemotherapy patients who develop
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behavioral interventions, pharmacologic interventions, or both are
effective with chemotherapy patients who are anxious but not
nauseous before infusions has yet to be investigated.
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