VOLUME 27 䡠 NUMBER 36 䡠 DECEMBER 20 2009
JOURNAL OF CLINICAL ONCOLOGY
From the School of Nursing,
Midwifery, and Social Work, Univer-
sity of Manchester; and Departments
of Clinical Oncology, Medical Oncol-
ogy, and Nursing Administration; and
Clinical Trials Unit, Christie Hospital
National Health Service Foundation
Trust, Manchester, United Kingdom.
Submitted October 23, 2008; accepted
July 30, 2009; published online ahead
of print at www.jco.org on November
16, 2009.
Supported by Roche Products Ltd
through an unrestricted grant.
Authors’ disclosures of potential con-
flicts of interest and author contribu-
tions are found at the end of this
article.
Corresponding author: Alexander
Molassiotis, RN, PhD, University of
Manchester, School of Nursing,
University Place, Manchester, M13
9PL, United Kingdom; e-mail: alex
.molassiotis@manchester.ac.uk.
The Appendix is included in the
full-text version of this article,
available online at www.jco.org.
It is not included in the PDF version
(via Adobe® Reader®).
© 2009 by American Society of Clinical
Oncology
0732-183X/09/2736-6191/$20.00
DOI: 10.1200/JCO.2008.20.6755
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O R I G I N A L R E P O R T
Effectiveness of a Home Care Nursing Program in the
Symptom Management of Patients With Colorectal and
Breast Cancer Receiving Oral Chemotherapy:
A Randomized, Controlled Trial
Alex Molassiotis, Sarah Brearley, Mark Saunders, Olive Craven, Andrew Wardley, Carole Farrell, Ric Swindell,
Chris Todd, and Karen Luker
A B S T R A C T
Purpose
To assess the effectiveness of a symptom-focused home care program in patients with cancer
who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of
life, and service utilization.
Patients and Methods
A randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal
(n ⫽ 110) and breast (n ⫽ 54) cancers who were receiving oral capecitabine. Patients were
randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks
(ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of
the patients’ participation in the trial, and validated self-report tools assessed anxiety, depression,
and quality of life.
Results
Significant improvements were observed in the home care group in relation to the symptoms of
oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all
P ⬍ .05). This improvement was most significant during the initial two cycles. Unplanned service
utilization, particularly the number of inpatient days (57 v 167 days; P ⫽ .02), also was lower in the
home care group.
Conclusion
A symptom-focused home care program was able to assist patients to manage their treatment
adverse effects more effectively than standard care. It is imperative that patients receiving oral
chemotherapy are supported with such programs, particularly during initial treatment cycles, to
improve their treatment and symptom experiences.
J Clin Oncol 27:6191-6198. © 2009 by American Society of Clinical Oncology
Home care nursing (HCN) may be a poten-
INTRODUCTION
tiallyvaluableservicetopatientsreceivingoralchem-
Oral chemotherapy is an attractive option in the otherapy, and it may be an alternative to other forms
treatment of patients with cancer because of its of care. In one of the first randomized trials of
convenience and ease of administration.1 Cape- HCN,7 patients with lung cancer (n ⫽ 78) were
citabine (Xeloda, Hoffmann-La Roche, Nutley, assigned to either oncology home care, standard
NJ) is orally administered chemotherapy for ad- home care, or routine care; patients who received
juvant/metastatic colorectal and metastatic breast HCN remained independent for a longer period of
cancers. Although capecitabine survival benefits time and showed lower symptom distress over time
compared with other standard treatments or than those in the routine care group. A quasi-
when patients are resistant to another chemother- experimental study of home care also showed that
apy have been established, a moderate-to-high the intervention had moderate effects on indicators
level of toxicity is apparent.2-5 Reductions may be of continuity of care (ie, communication or satisfac-
necessary because of toxicity in as many as 26% of tion with care).8 A significant survival effect and
non–pretreated patients and in 45% of pre- notable improvements in physically and socially vul-
treated patients.6 nerable older patients with cancer also have been
© 2009 by American Society of Clinical Oncology 6191
Copyright © 2018 American Society of Clinical Oncology. All rights reserved.
 Molassiotis et al

shown.9,10 Despite these results, the evidence is uncertain, and a sys-
tematic review of home care programs for patients with incurable
cancer found the programs’ effectiveness to be unclear.11
A review of symptom management interventions that have
relevance to capecitabine-related toxicity was undertaken (Appen-
dix Table A1, online only). A synthesis of the management of com-
mon toxicities informed this trial.12-29 The symptom management
model by Dodd30 was used as the theoretical framework underlying
this study.
The aim of the study was to assess the effectiveness of a symptom-
focused HCN program (in addition to standard care) for patients
receiving oral capecitabine in terms of toxicity management, quality of
life indicators, and service utilization.
PATIENTS AND METHODS
A randomized, controlled trial was used. The study gained approval from the
hospital and the university research ethics committees. Consecutive eligible
patients were recruited and, on receipt of signed consent, were allocated to
receive either standard care or HCN. Random assignment was carried out by
an independent statistician through a computer-generated program. No clini-
cian or researcher could anticipate or direct allocation.
protocols. The key element was one standard home visit during the first week
of capecitabine. During this visit, the chemotherapy and its adverse effects were
discussed, questions patients had were sought and answered, and support was
given. This visit lasted 1 to 1.5 hours. Subsequent home visits were offered
when patients experienced multiple grade 3 toxicities or had difficulty coping
with the chemotherapy. All home care patients also received one monitoring
phone call per week during all cycles (ie, a minimum of 18 phone contacts
during the intervention). These lasted between 10 and 25 minutes and in-
cluded toxicity assessment followed by discussion of possible strategies to deal
with the reported symptoms. Patients also had access to a 24-hour, on-call,
specialist nursing service.
A log of contact time was kept by each HCN. Most patients received a
minimum of 3 hours of total contact with the HCNs, but this increased to
a maximum of 10 hours for patients who required additional support.
When multiple grade 3 toxicities occurred, the HCNs assessed patients to
ascertain if they could be managed at home or whether they required
additional medical support, such as earlier consultations with their clini-
cians. When life-threatening symptoms, such as grades 3 to 4 diarrhea/
mucositis or signs of hematologic toxicity/neutropenia occurred, HCNs
advised patients to attend their emergency departments or cancer centers
and facilitated these visits. Family members/caregivers often were present
at the home visits and listened to the strategies discussed but were not the
recipients of the intervention.

Sample and Setting Table 1. Sociodemographic and Clinical Characteristics of the Sample
The sample consisted of patients who started capecitabine and who had
colorectal or breast cancer (ratio of 2:1) that was both adjuvant and metastatic. All Patients Experimental Control
(N ⫽ 164) Group Group
Stratification took place on the basis of diagnosis. Patients were recruited from
a cancer hospital in the United Kingdom during a 24-month period. The Characteristic No. % No. % No. %
duration of follow-up was 4.5 months (ie, six cycles of chemotherapy). Sex
Patients age 18 years or older who had breast or colorectal cancer, had life Female 102 62.2 50 60.2 52 64.2
expectancy longer than 6 months, were starting capecitabine, were able to self Male 62 37.8 33 39.8 29 35.8
care, and were able to communicate in English were recruited. Patients who Marital status
had past experiences of HCN programs and those who were living outside a Single 16 9.8 11 13.3 5 6.2
35-mile radius from the hospital were excluded. All patients had regular visits Married 119 72.5 55 66.3 64 79
to their physicians at the end of each cycle for clinical evaluation and Divorced/separated 11 6.7 6 7.2 5 6.2
blood tests. Widowed 18 11 11 13.3 7 8.6
Occupation
Sample Size Retired 90 54.9 44 53 46 56.8
On the basis of toxicity data presented by van Cutsem et al4 to observe a Housewife 8 4.9 5 6 3 3.7
0.5 standard deviation (SD) difference with 80% power by using a two-tailed Education/health 23 14 10 12 13 16
statistical test at the P ⬍ .05 significance level, 64 occurrences per group would Manual 11 6.7 4 4.8 7 8.6
be needed; an additional 10% would be required for nonparametric tests to be Clerical/administration 20 12.2 12 14.5 8 9.9
used. Hence, the minimum sample size for the study had to be 142 patients. Unemployed 1 0.6 1 1.2 —
Unable to work because
Standard Care of ill health 11 6.7 7 8.4 4 4.9
The standard care consisted of information about the drug and its ad- Diagnosis
verse effects, which was provided by the clinicians and accompanied by written Colorectal cancer 110 67.1 60 72.3 50 61.7
information. Antiemetics, antidiarrheal medication, and mouthwashes were Breast cancer 54 32.9 23 27.7 31 38.3
prescribed to take as needed, whereas hand creams and pyridoxine could be Stage
prescribed as symptoms developed. Patients were given the hospital’s 24-hour I 2 1.2 0 2 2.4
emergency hotline phone number. A research associate assessed patients’ II 26 15.9 13 15.6 13 16
symptoms at baseline and every week thereafter by phone without providing III 84 51.2 28 45.8 46 56.9
medical/nursing advice. IV 52 31.7 32 38.6 20 24.7
Treatment intent
Intervention: Home Care Nursing Program Palliative 98 59.7 54 65 42 51.9
The HCN program was developed on best evidence from the literature. Adjuvant therapy 68 40.3 29 35 39 48.1
Written symptom management protocols were developed in collabora- Capecitabine dose received
tion with the clinical team and were based on current recommenda- as planned by cycle
tions,12-29 including evidence-based pharmacologic and nonpharmacologic/ 1-2 53.7 43.3
self-management interventions that the specialist HCNs could use or suggest 3-4 37.7 36.5
to patients when problems developed (Appendix Table A1). 5-6 31.6 33.3
The HCN program was multimodal and included symptom assessment,
patient education, and/or treatment of symptoms on the basis of agreed

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 Home Care Support in Patients Receiving Oral Chemotherapy

The home care team consisted of five nurses with training and experience
both in home care and cancer care who were contracted independently
through a private health company (Healthcare-at-Home, Burton Upon Trent,
Staffordshire, United Kingdom). Operating according to a carefully moni-
tored protocol, they received additional training relevant to the intervention.
Regular meetings were held to discuss the delivery of the intervention and trial
progress. They also carried out toxicity assessments weekly. Interrater reliabil-
ity between assessors and the research associate was assessed using Kendall’s ␶
coefficient, and complete agreement was achieved; however, agreement for the
scoring of hand-foot syndrome was lower but was not significant (r ⫽ 0.58;
P ⫽ .31).
Outcome Measures
The primary outcome was toxicity grading, which was completed at
baseline and weekly thereafter for the duration of the intervention. The inten-
sity of nine clinical adverse effects (ie, oral mucositis, hand-foot syndrome,
diarrhea, constipation, nausea, vomiting, pain, fatigue, and insomnia) was
graded by using a four-point Likert-type scale according to the National
Cancer Institute Common Toxicity Criteria (NCI-CTC).31 Toxicity scores
were transformed into a single composite score of all symptoms together,
which was used as the primary outcome of the trial.
Secondary outcomes included the Hospital Anxiety and Depression
Scale, which was completed at baseline and every 6 weeks. This is a scale that is

Assessed for eligibility

(n = 239)

Excluded (n = 75)
Not meeting inclusion criteria (n = 2)
Refused to participate (n = 72)
Other reasons (n = 1)

Randomly allocated
(n = 164)

Allocated to standard care (n = 81) Allocated to home care (n = 83)

Received standard care (n = 81) Received home care (n = 83)
Did not receive standard care (n = 0) Did not receive home care (n = 0)

Cycles 1-2 (n = 81) Cycles 1-2 (n = 83)

Completed cycle 2 (n = 74) Completed cycle 2 (n = 76)
Treatment stopped (n = 7) Treatment stopped (n = 7)
Cardiac/renal problems (n = 3) Cardiac/renal problems (n = 2)
Death (n = 1) Death (n = 1)
Patient decision (n = 1) Patient decision (n = 1)
Toxicity-related stoppage (n = 1) Toxicity-related stoppage (n = 2)
Unfit for treatment (n = 1) Unfit for treatment (n = 1) Fig 1. CONSORT diagram of the trial
flow. XRT, radiation therapy.

Cycles 3-4 (n = 74) Cycles 3-4 (n = 76)

Completed cycle 4 (n = 63) Completed cycle 4 (n = 62)
Treatment stopped (n = 11) Treatment stopped (n = 14)
Death (n = 2) Cardiac/renal problems (n = 1)
Disease progression (n = 2) Death (n = 1)
Toxicity-related stoppage (n = 2) Disease progression (n = 5)
Unfit for treatment (n = 5) Patient decision (n = 2)
Surgery/XRT (n = 1)
Toxicity-related stoppage (n = 1)
Unfit for treatment (n = 3)

Cycles 5-6 (n = 63) Cycles 5-6 (n = 62)

Completed cycle 6 (n = 37) Completed cycle 6 (n = 43)
Treatment stopped (n = 26) Treatment stopped (n = 19)
Arbitrary reason (n = 5) Arbitrary reason (n = 1)
Death (n = 1) Completion of 4 cycle clinical trial (n = 6)
Completion of 4 cycle clinical trial (n = 11) Disease progression (n = 6)
Disease progression (n = 4) Patient decision (n = 1)
Toxicity-related stoppage (n = 3) Surgery/XRT (n = 1)
Unfit for treatment (n = 2) Unfit for treatment (n = 3)
2/3 weekly cycles (n = 1)

Analyzed cycle 1-2 (n = 74) Analyzed cycle 1-2 (n = 76)

Cycle 3-4 (n = 63) Cycle 3-4 (n = 62)
Cycle 5-6 (n = 37) Cycle 5-6 (n = 43)

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Copyright © 2018 American Society of Clinical Oncology. All rights reserved.
 Molassiotis et al
widely used for patients with cancer, and it evaluates both dimensional and
categoric aspects of anxiety and depression levels (with seven items each).32,33
Secondary outcomes also included the European Organisation for Re-
search and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-
QLQ-C30), which was completed at baseline and every 6 weeks. This is a
30-item, quality-of-life scale that is widely used in cancer research and that
includes assessment of five functional areas, a global health status score, and
single measures of symptom severity. Good-to-excellent validity, reliability,
sensitivity, and interpretability have been reported.34,35
Health Services Utilization
Evaluation of health services utilization was completed at the end of all
cycles. A checklist was developed to assess the number of times patients used
their primary health care provider (ie, general practitioner [GP]), used hospital
staff, had unplanned outpatient attendance, had hospital admissions, or had
phone calls to treating oncologists or specialist nurses. These utilizations rep-
resented primarily toxicity management and also disease progression events.
Data Analysis
Data analyses were carried out by an independent statistician at the
clinical trials unit where the trial took place. Toxicity was analyzed by
cumulating the scored toxicity within each cycle of treatment at the assess-
ment points every 3 weeks (or every 2 weeks for two-weekly cycles). This
summed score was cumulated during the six cycles of treatment (nine for
two-weekly cycles), and three main assessment loci were selected for anal-
ysis. As baseline scores were found to be similar in the two groups, the
assessment loci reflected toxicity from start of treatment to end of cycles 2,
4, and 6. For those completing cycles at the assessment loci, the sum of the
score at each locus is a surrogate for the area under the curve, because, in
ordinal terms, the score has the same ranking as the area.36 Median scores
with minimum and maximum values (instead of interquartile ranges) are
presented, as the data were skewed.
A metric (cumulated) score was used to aggregate the scores of all
symptom assessments. Analysis was carried out by using a linear, mixed-
effects model, which enabled a single assessment of the primary outcome to
be made and which permitted additional interpretation of the clinical
significance of the results. As there was no difference in the baseline scores,
a fitted, pooled, mean baseline score was used in the model. A transforma-
tion was performed beforehand because of skewed data by taking the
square root of each metric score, which resulted in the data being more
normally distributed. The score for all symptom assessments was aggre-
gated across cycles 1 to 2, 3 to 4, and 5 to 6, which provided three metric (ie,
composite) scores in each arm.
Calculations also were undertaken for anxiety/depression and quality
of life by using the Mann-Whitney U tests (baseline data) or Friedman’s
two-way nonparametric analysis of variance by ranks between the two trial
arms. The last value carried forward was imputed to deal with missing data,
and it was used when single assessments were missing and so as not to
impute whole cycles of missing data. Missing values in the control and
experimental groups were low; (cycles 1 to 2, 0.66% and 2.69%, respec-
tively; cycles 3 to 4, 0.51% and 4.12%, respectively; cycles 4 to 5, 1.11% and
5.6%, respectively).
RESULTS
Sociodemographic and Clinical Characteristics
We recruited 164 patients. Most were women, were married,
were retired, and had a diagnosis of colorectal cancer (Table 1). The
mean age of the sample was 61.08 years (SD, 12.73; range, 26 to 85
years). There was no significant difference in the mean age of the two
groups: the control patients had a mean age of 60.8 years (SD, 12.7),
and the experimental patients had a mean age of 61.3 (SD, 12.8;
6194 © 2009 by American Society of Clinical Oncology
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unpaired t test P ⫽ .81). The mean time since diagnosis was 26.9
months (SD, 37.5). Participants received a capecitabine mean dose of
1,111.54 mg/m2 twice daily (range, 625 to 1,250 mg/m2). The majority
received capecitabine as first- (43.3%) or second-line (32.3%) chem-
otherapy, and 93.9% received treatment on cycles of every 3 weeks.
Capecitabine was given as single agent in 89% of patients, and the
remainder received it as part of a combination protocol with either
oxaliplatin, irinotecan, docetaxel, vinorelbine, or mitomycin; this re-
flected the changing use of capecitabine.
Diagnosis, line of chemotherapy, treatments every 3 weeks and
every 2 weeks, and single-agent or combination protocols were evenly
spread in the two arms. Half the sample (n ⫽ 81) completed assess-
ments for all points during the six cycles of chemotherapy. Reasons for
dropping out are presented in the CONSORT diagram (Fig 1). Only
eight patients needed one extra home visit, and two patients needed
two extra home visits. The capecitabine dose received was similar in
both groups (all P ⬎ .05; Table 1).
Symptom Toxicity
The presenting toxicity (ie, at baseline) was compared by
using the Mann-Whitney U test, and no differences were found
(P ⫽ .66) on the basis of the single, composite, baseline score of all
nine symptoms together. This was true for the scores of the total
sample as well as for the three subsets of patients (ie, those com-
pleting cycles 1 to 2, 1 to 4, and 1 to 6). Linear, mixed-effects
modeling analysis on the single metric (ie, composite) score
showed that there were highly significant differences in the two
groups favoring the homecare arm, and the mean fitted values over
cycles 1 to 2, 3 to 4, and 5 to 6 in the standard-care arm were 14.7,
15.1, and 16.7, respectively, in the intervention arm, the mean
fitted values were as follows: 6.2, 9.3, and 11.2 (Fig 2). Table 2
presents the symptom changes in more detail. All symptoms sig-
nificantly improved during cycles 1 to 2, with the exception of
hand-foot syndrome and vomiting. Significant symptom improve-
ments were maintained in cycles 1 to 4 and in 1 to 6, except for
hand-foot syndrome, vomiting (cycles 1 to 4 and 1 to 6,) and
fatigue (cycles 1 to 6). In all occurrences, the experimental group
scored significantly less toxicity than the control group. The vast
majority of the observed toxicities were grade 1 or 2. Fatigue was
20
Mean Global Score
15
with 95% CI
10
5
Standard care arm
Home care arm
0
Cycle 1-2 Cycle 3-4 Cycle 5-6
P < .0001 P = .0002 P = .0006
Fig 2. Comparison of global toxicity score between standard care and home
care arms. Black bars represent 95% CI.
JOURNAL OF CLINICAL ONCOLOGY
 Home Care Support in Patients Receiving Oral Chemotherapy

Table 2. Symptom Assessment Results Between Experimental and Control Groups

Standard Care Home Care
Symptom by Cycle
Assessed Mean Median Min Max Mean Median Min Max P
Cycles 0-2 n ⫽ 74 n ⫽ 76
Oral mucositis 1.9 1 0 13 0.8 0 0 8 ⬍ .0005
Hand-foot syndrome 3.3 2 0 18 2.1 1 0 11 .080ⴱ
Diarrhea 2.1 1 0 12 0.9 0 0 7 .002
Constipation 1.1 0 0 6 0.4 0 0 5 .003
Nausea 2.4 2 0 10 1.1 0 0 9 .002
Vomiting 0.7 0 0 5 0.3 0 0 5 .062ⴱ
Pain 2.6 2 0 11 1.6 0 0 10 .001
Fatigue 6.3 6 0 18 4.4 4 0 4 .005
Insomnia 2.8 2 0 11 0.5 0 0 9 ⬍ .0005
Cycles 0-4 n ⫽ 63 n ⫽ 62
Oral mucositis 3.4 2 0 22 1.2 0 0 8 .001
Hand-foot syndrome 9.0 8 0 31 7.4 6 0 26 .250ⴱ
Diarrhea 3.7 2 0 19 1.8 1 0 15 .031
Constipation 2.0 1 0 10 0.6 0 0 5 .002
Nausea 4.0 2 0 18 1.8 1 0 15 .006
Vomiting 1.0 0 0 10 0.3 0 0 3 .106ⴱ
Pain 5.3 5 0 21 2.3 0.5 0 20 ⬍ .0005
Fatigue 12.0 12 0 34 9.0 10 0 24 .010
Insomnia 5.7 4 0 26 0.7 0 0 12 ⬍ .0005
Cycles 0-6 n ⫽ 37 n ⫽ 43
Oral mucositis 3.8 2 0 27 1.6 0 0 8 .035
Hand-foot syndrome 16.7 17 1 36 14.2 13 0 31 .279ⴱ
Diarrhea 5.5 3 0 24 2.5 1 0 19 .009
Constipation 2.3 1 0 18 0.8 0 0 8 .006
Nausea 5.3 3 0 21 2.3 1 0 10 .036
Vomiting 0.7 0 0 7 0.5 0 0 3 .928ⴱ
Pain 6.3 5 0 20 2.9 1 0 24 ⬍ .0005
Fatigue 15.1 15 0 36 14.8 15 0 25 .927ⴱ
Insomnia 6.8 5 0 34 0.8 0 0 12 ⬍ .0005

NOTE. Data are the summed scores at each of three assessment points. Higher values result from higher toxicity scores. The large number of zero-value median
scores, particularly in the initial cycles, is due to no toxicity occurrence in greater than 50% of patients. These mask the differences between the two arms; the
differences are more effectively described with the mean values. Standard care is control; home care is experimental.
Abbreviations: min, minimum; max, maximum.
ⴱ
Not significant.

the most common symptom experienced by up to 90% of the Secondary Outcomes

patients and was maintained at high levels across all cycles, while Anxiety improved in both groups over time; however, there was a
hand-foot syndrome was the only symptom that was increased trend in the experimental group to have higher improvement than the
over all cycles (Fig 3). control group (P ⫽ .001; n ⫽ 35 in experimental group; P ⫽ .023;
n ⫽ 34 in the control group; Fig 4). There were no differences between
the two groups in depression. Quality-of-life scores were similar be-
tween the two arms, with the exception of financial problems, which
Fatigue
Hand-Foot was highly significant (improved outcome) in the homecare group
syndrome
(P ⫽ .004, n ⫽ 36, experimental group; P ⫽ .248, n ⫽ 30, control
Pain
Insomnia
group). The symptoms of diarrhea and pain were significant when the
Diarrhea results from both groups were combined, but this significance was lost
Nausea when analyzed separately (pain, overall, P ⫽ .031; P ⫽ .11, n ⫽ 34,
Mucositis control group; P ⫽ .20, n ⫽ 37, experimental group; diarrhea, overall,
Constipation
Standard care P ⫽ .018, P ⫽ .38; n ⫽ 30, control group; and P ⫽ .051 n ⫽ 35,
Vomiting Home care
experimental group). There were no differences in any of the out-
Same values
comes between patients with colorectal and breast cancers or younger
0 100/0 100/0 100/0 100/0 100/0 100 (⬍ 65 years) and older patients (65 and older; Mann-Whitney U test
Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 P ⫽ .82). There were no differences between the two groups in relation
Fig 3. Percentage frequency of symptoms over the six cycles of chemotherapy
to chemotherapy discontinuations, dose reductions, patients com-
between the experimental and control group. pleting chemotherapy and completing chemotherapy on time.

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 Molassiotis et al

oral chemotherapy. Results demonstrate that a HCN symptom-

Anxiety
10
oriented supportive care intervention can decrease symptom burden
and can lead to reduced service utilization. Although findings from
randomized trials of home care7,37,38 are relatively disparate in the
literature, they broadly concur with the findings of the present study.
8 The improvement in toxicity was more evident in the first two
cycles of chemotherapy (ie, first 6 weeks) and was supported by both
HADS Anxiety Score

the single global toxicity score (Fig 2) and the analysis of each individ-
6 ual symptom (Table 2). After that period, although improvements in
most symptoms were maintained, the effectiveness of the intervention
somewhat decreased, as many symptoms (ie, vomiting) reached a
plateau. This suggests that the most crucial time to provide a support-
4
ive care intervention in patients receiving capecitabine is during the
first two cycles of treatment. Although patients generally receive
information and education about their chemotherapy before start-
2 ing treatment, they may feel overwhelmed with such information,
and re-education and support during the first few weeks of treatment
Standard seems an appropriate and useful approach. Also, such an intervention
Home maintains better continuity of care and a more positive experience of
0 1 2 3 4 treatment. Its generic approach to symptom management makes this
intervention appropriate for other oral chemotherapies.
Assessment No.
When we unpacked the intervention to identify the elements that
Fig 4. Changes in anxiety levels between experimental and control groups. The
have led to its effectiveness, we saw clearly that the variety of evidence-
data shown in each vertical line are as follows: lower quartile (lower point) and based measures utilized by HCNs in managing symptoms have been
upper quartile (upper point); median (⫻, which are the values joined across the beneficial, as was the timely nature of intervention, early referral, and
graph); and mean (large horizontal bar). All eight lines have a minimum of zero.
Maximum values from left to right are as follows: 17, 15, 17, 13, 20, 16, 13, and additional nonpharmacologic support. Duration is also key: this in-
15. HADS, Hospital Anxiety and Depression Scale. tervention lasted 18 weeks, and the literature highlights that programs
longer than 4 weeks are more likely to be beneficial than shorter
programs.10 Weekly monitoring phone calls were carried out in both
Service Utilization groups, which may have contributed to the improvement observed in
For this secondary objective, the nominal data collected was both groups over time. Finally, the impact of the nurse-patient rela-
grouped in four categories: number of visits to GPs; calls to the hospi- tionship, reassurance, and empowerment39 patients experienced
tal emergency hotline; occasions of other health care utilization (in- through this supportive home care environment may also have con-
cluding extra visits to the hospital, ambulance use, emergency tributed to the improvements.
department attendance), and d) inpatient days. Although visits to GPs It is notable that significant improvement in symptom toxicity is
were similar in the two arms, there was significantly lower number of not reflected by quality-of-life changes. The reasons for this may be
calls to the hospital emergency hotline, lower utilization of other multifaceted. The quality-of-life scale may lack sensitivity to detect
health care services, and lower number of inpatient days in the exper- changes that have happened in preceding weeks. The specific modules
imental group (Table 3). for colorectal and breast cancers were not used in this study to mini-
mize patient burden; however, in retrospect, these may be more sen-
sitive. The literature also suggests that the timing of quality-of-life
DISCUSSION
assessments may be an important source of error in cancer trials.40
This timing was not controlled in our study, as patients self completed
To our knowledge, this randomized trial is the first supportive care
the scale at home. In addition, the content of the scale may lack
trial to date testing the effects of an intervention in patients receiving
relevancy to individual patients, and scales may fail to distinguish
between the statistical and clinical significance of findings.41
Because the use of oral chemotherapy is steadily increasing, it
Table 3. Service Utilization Data in the Two Trial Groups Across Cycles seems imperative to find ways to support patients at home, particu-
Experimental Control larly because oral chemotherapy is often given to elderly and frail
Service Used Group Group P patients. An HCN, symptom-focused intervention appears to be an
No. of visits with GP 38 58 .09 effective way of supporting patients. Although this may not be feasible
No. of calls with emergency for large numbers of patients who receive oral chemotherapy, resource
hotline 32 91 .0005
savings in other areas of health care utilization may offset the HCN
No. of visits with other health
service utilization contact 33 74 .008 costs. Overall, health care utilization seemed to be lower in the inter-
No. of inpatient days 57 167 .02ⴱ vention arm. Although this part of the study was exploratory in nature,
Abbreviation: GP, general practitioner.
the lower utilization in the intervention arm suggested the hypothesis
ⴱ
Significant only for cycles 1-2. that symptom management interventions may have the potential to
decrease overall care costs. Such costs should be monitored carefully in

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 Home Care Support in Patients Receiving Oral Chemotherapy

future studies. Future studies also should show if key elements of the
current intervention can be effective if delivered in more cost- and
labor-effective manners. For example, there is increasing evidence that
nurse-led telephone follow-up is effective and meets the psychosocial
and informational needs of patients with cancer.42,43
Although patients who receive oral chemotherapies experi-
ence significant levels of toxicity, it is imperative that health pro-
fessionals support them in the community to manage symptom
burden and improve quality of life. The HCN approach, although
resource intensive, was effective in managing symptom toxicity. A
more proactive symptom management approach should translate
into improved outcomes for patients and a more positive experi-
ence of the treatment trajectory.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Although all authors completed the disclosure declaration, the following
author(s) indicated a financial or other interest that is relevant to the subject
matter under consideration in this article. Certain relationships marked
with a “U” are those for which no compensation was received; those
relationships marked with a “C” were compensated. For a detailed
description of the disclosure categories, or for more information about
ASCO’s conflict of interest policy, please refer to the Author Disclosure
Declaration and the Disclosures of Potential Conflicts of Interest section in
Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory
Role: Andrew Wardley, F. Hoffmann-La Roche (C); Carole Farrell, F.
Hoffmann-La Roche (C) Stock Ownership: None Honoraria: Mark
Saunders, F. Hoffmann-La Roche; Olive Craven, F. Hoffmann-La
Roche; Andrew Wardley, F. Hoffmann-La Roche; Carole Farrell, F.
Hoffmann-La Roche Research Funding: Alex Molassiotis, Roche
Products (UK); Sarah Brearley, F. Hoffmann-La Roche; Chris Todd,
Roche Products (UK); Karen Luker, F. Hoffmann-La Roche Expert
Testimony: None Other Remuneration: Carole Farrell, F.
Hoffmann-La Roche
AUTHOR CONTRIBUTIONS
Conception and design: Alex Molassiotis
Provision of study materials or patients: Mark Saunders, Olive Craven,
Andrew Wardley, Carole Farrell
Collection and assembly of data: Alex Molassiotis, Sarah Brearley,
Ric Swindell
Data analysis and interpretation: Alex Molassiotis, Sarah Brearley, Ric
Swindell, Chris Todd, Karen Luker
Manuscript writing: Alex Molassiotis, Sarah Brearley, Mark Saunders,
Olive Craven, Andrew Wardley, Carole Farrell, Ric Swindell, Chris Todd,
Karen Luker
Final approval of manuscript: Alex Molassiotis, Sarah Brearley, Mark
Saunders, Olive Craven, Andrew Wardley, Carole Farrell, Ric Swindell,
Chris Todd, Karen Luker

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■ ■ ■

JCO Announces New Requirement for Phase III Studies

Effecve this month, JCO requires authors of phase III reports to include protocol informaon in
their submissions. JCO believes that for the editors and reviewers to properly peer review a
submission, a redacon of the protocol for all phase III studies must be provided.

Protocol informaon must include the eligibility criteria, study schema and dose modificaons,
and a stascal secon (including end points). This file will only be available to the editors and
reviewers during the peer review process.

For more informaon about this new requirement, see the Submission Requirements secon of
the Informaon for Contributors page, at jco.ascopubs.org/ifc/requirements.dtl

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