2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

TREATMENT APPROACHES IN CHILDREN
which the patient was admitted to hospital and then discharged
early while still receiving empiric antibiotics for FN.
Outpatient management was associated with a similar risk
of treatment failure compared with inpatient management
(rate ratio [RR] 0.81, 95% CI 0.55 to 1.28, p � 0.28) where
RR � 1 favored inpatient care. In interpreting this RR, it is
important to realize that failure was biased against outpatient
care because readmission, a criterion for failure, is only
applicable to outpatients. There was no difference in mortality
(RR 1.11, 95% CI 0.41 to 3.05, p � 0.83). In a stratified
analysis of the two pediatric studies, 16,17 results were similar
to the overall analysis.
Although this review provides evidence for the safety of
outpatient management, it includes only two studies in
children, and, in total, 278 pediatric subjects were studied.
Consequently, this analysis may have had insufficient power
to evaluate outpatient care in pediatric FN. Thus, we subsequently
conducted a systematic review in which we evaluated
data from all prospective trials in pediatric FN that
studied a homogeneous, initial antibiotic regimen. 18 There
were 16 trials in which either outpatient or inpatient management
were established within the first 24 hours of
treatment-initiation in low-risk FN. There was no increase
in treatment failure (including modification of antibiotics)
with outpatient management in comparison with inpatient
management (15% compared with 27%, p � 0.04). The rate
of adverse events leading to antibiotic discontinuation was
similar (1% compared with 2%, p � 0.39). Among the 953
outpatients, there were no infection-related deaths.
In summary, when combining data from prospective observational
and randomized trials in pediatric patients,
similar outcomes were observed between those treated as
outpatients or inpatients. However, outpatient management
should only be instituted if the child can be confidently
classified as low-risk, and if the social circumstances and
local infrastructure support ambulatory management.
Consequently, if the child, family, and health care facility
characteristics support outpatient care, then ambulatory
management may be offered. Outpatient FN programs in
KEY POINTS
● Prospective single-arm and randomized trials have
provided evidence for the efficacy and safety of outpatient
management and oral antibiotic administration
for low-risk children with fever and neutropenia.
● Outpatient oral management may be associated with
a higher risk of readmission in children, although
other outcomes such as treatment failure and discontinuation
of the regimen because of adverse effects
are similar.
● Outpatient management is cost-saving when compared
to an inpatient or an early discharge strategy.
● Anticipated child quality of life as reported by parents
is higher with outpatient strategies.
● When comparing inpatient with outpatient management
of low-risk fever and neutropenia, the most
preferred option is variable, and frequently, parents
and children will prefer inpatient care.
children vary considerably in terms of frequency of follow up
and nature of follow up (for example, telephone contact
compared with a clinic visit). Future work should consider
minimal and optimal approaches to follow outpatient children
with FN.
Oral versus Parenteral Antibiotic Administration
Regardless of whether low-risk children with FN are
treated in the outpatient or inpatient setting, another question
relates to the optimal mode of antibiotic administration.
Oral antibiotic administration may be desirable because it
facilitates outpatient management, is more convenient, and
is usually less expensive compared with intravenous antibiotic
administration. However, there are several unique issues
with oral medication administration in young children.
Issues to consider include the likelihood that the child can
and will accept oral therapy in available formulations given
the child’s level of cooperation. First, very young children
may not be able to swallow pills or capsules, and, thus, oral
antibiotics are only feasible in this age group if the medication
is available in a liquid formulation. Second, taste of oral
medication is a much more important issue in young children
compared to adults, as an unpalatable drug may be
refused. Third, children may refuse all oral medications
regardless of taste, particularly if they feel unwell. Furthermore,
the likelihood that the child will accept oral therapy
may change if nausea, vomiting, or mucositis are present.
Oral antibiotic administration may be initiated at the onset
of the FN episode or following a short period of parenteral
administration before transitioning to oral administration
(step-down management).
Two meta-analyses of RCTs evaluated oral and intravenous
antibiotic administration for FN. One study of 2,770
patients included both outpatients and inpatients 7 whereas
the second study of 1,595 patients was restricted to outpatients.
15 Neither study restricted their review to low-risk FN
patients. Both reviews showed similar results with no difference
in treatment failure (including modification), overall
mortality, or adverse effects of antibiotics. These findings
were demonstrated both among combined adult and pediatric
analyses, as well as in stratified analyses of pediatric
studies alone. However, a stratified analysis of five pediatric
RCTs demonstrated that intravenous outpatient management
was associated with a lower rate of readmission
compared with oral outpatient management (RR 0.52, 95%
CI 0.24 to 1.09, p � 0.08). 15
More information about the efficacy and safety of oral
antibiotic administration was derived from an analysis of
prospective pediatric trial data comparing oral and parenteral
antibiotic therapy initiated within 24 hours of treatment
initiation in low-risk FN. 18 Oral antibiotics used in
these studies were fluoroquinolone monotherapy (7 studies
with 581 patients), fluoroquinolone and amoxicillinclavulanate
(3 studies with 159 patients), and cefixime
(1 study with 45 patients). The review found no difference in
treatment failure (including modification) among children
who received oral compared with intravenous antibiotic
therapy (20% compared with 22%, p � 0.68). The rate of
antibiotic discontinuation because of adverse events was
similar between the oral and intravenous regimens (2%
compared with 1%, p � 0.73). There were no infectionrelated
deaths among the 676 children given oral antibiotics.
To summarize, there were more readmissions among chil-
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