1. Art and Diseño

ARTICLE IN PRESS
European Journal of Oncology Nursing (2004) 8, S31–S40
www.elsevier.com/locate/ejon
Management of hand-foot syndrome in patients
treated with capecitabine (Xelodas)
Yvonne Lassere, Paulo Hoff
Clinical Protocol Administration, MD Anderson Cancer Center, 1515 Holcombe Unit 426,
Houston TX 77030, USA
KEYWORDS:
Capecitabine;
Xelodas;
Hand-foot syndrome
Summary Comparative trials of capecitabine (Xelodas) versus 5-FU/LV in
metastatic colorectal cancer have shown that hand-foot syndrome (HFS) was the
only clinical adverse event occurring more frequently with capecitabine. Most
patients with HFS present with dysesthesia, usually with a tingling sensation in the
palms and soles of the hands and feet. This can progress in 3–4 days to burning pain
plus well-defined symmetric swelling and erythema. The hands tend to be more
commonly affected than the feet, and might even be the only area affected in some
patients. HFS can interfere with the general activities of daily living, especially
when blistering, moist desquamation, severe pain or ulceration occurs. While HFS is
manageable, if ignored it can progress rapidly. However, dose interruption and
reduction of capecitabine usually leads to a rapid reversal of signs and symptoms
without long-term consequences. Nurses play a key role in educating patients how to
recognise HFS, when to interrupt treatment and how to adjust the dose to maintain
effective therapy with capecitabine over the long term. It is particularly important
that patients and nurses are aware that dose interruption/reduction does not affect
the overall antitumour efficacy of capecitabine.
r 2004 Elsevier Ltd. All rights reserved.
Zusammenfassung Vergleichende Versuche mit Capecitabine (Xelodas) im Vergleich zu 5-FU/LV bei metastasierendem kolorektalem Karzinom haben gezeigt,
dassdas Hand-FuX-Syndrom (HFS) die einzige Nebenwirkung ist, die mit Capecitabine
ha
¨ufiger auftritt. Bei den meisten Patienten mit HFS tritt Dysa
¨sthesie auf,
normalerweise mit einem Prickeln auf den Handfla
¨chen und FuXsohlen. Dies kann
innerhalb von 3 bis 4 Tagen zu einem brennenden Schmerz und klar definierten
symmetrischen Schwellungen und Erythem fortschreiten. Die Ha
¨nde sind im
allgemeinen o
¨fter befallen als die Fu
¨Xe und ko
¨nnen bei einigen Patienten sogar
die einzigen befallenen Bereiche sein. HFS kann die normalen Verrichtungen
des ta
¨chtigen, besonders, wenn Blasenbildung, feuchte
ˇglichen Lebens beeintra
Corresponding author. Tel.: +1-713-792-6512; fax: +1-713-745-2845.
E-mail address: [email protected] (Y. Lassere).
1462-3889/$ - see front matter r 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ejon.2004.06.007
ARTICLE IN PRESS
S32
Y. Lassere, P. Hoff
Abschuppung, starke Schmerzen oder Geschwu
¨rbildung auftreten. Obwohl man HFS
behandeln kann, entwickelt es sich rapide, wenn man es ignoriert. Zeitweiliges
Absetzen oder eine Verminderung der Dosierung von Capecitabine fu
¨hrt jedoch
normalerweise zu einem raschen Abklingen der Anzeichen und Symptome ohne
langfristige Folgen. Das Pflegepersonal spielt eine fu
¨hrende Rolle dabei, die
Patienten darin zu unterweisen wie man HFS erkennt, wann man die Benandlung
unterbrechen sollte und wie man die Dosierung vera
¨ndert, um eine wirksame
Behandlung mit Capecitabine langfristig aufrecht zu erhalten. Besonders wichtig ist
dabei, dass Patienten und Pflegepersonal wissen, dass die Unterbrechung oder
Minderung der Dosierung die langfristige turnorbeka
¨mpfende Wirksamkeit von
Capecitabine nicht beeintra
ˇchtigt.
r 2004 Elsevier Ltd. All rights reserved.
Introduction
Hand-foot syndrome
Capecitabine (Xelodas) was specifically designed
for oral administration, to deliver 5-FU to the
tumour site and to avoid systemic 5-FU exposure
(Ishikawa et al., 1998; Miwa et al., 1998). As
discussed in article 1 in this Supplement (Sternberg
et al., 2004), the unique tumour-selective conversion of capecitabine to active 5-FU is achieved by a
3-step enzymatic process. The final step of the
conversion is mediated by the enzyme thymidine
phosphorylase, which is found at higher levels in
cancer cells compared with normal tissues. As a
result, more of the active anticancer agent 5-FU is
produced where it is needed (i.e. within cancer
cells rather than in healthy tissues).
Oral capecitabine is being increasingly accepted
into clinical practice as it permits convenient
administration in a home-based setting. Capecitabine tablets are taken orally twice daily approximately 12 h apart (after breakfast and after dinner)
for 2 weeks followed by a 1-week, treatment-free
period. After this 1-week ‘rest’ period, the patient
starts the next cycle. The normal recommended
dosage is 1250 mg/m2 twice daily, unless dose
reduction is indicated because of adverse events.
At this dosage, capecitabine is generally well
tolerated, with a low incidence of grade 3/4
adverse events (see article 2 in this supplement).
One of the most common adverse events associated
with its use in clinical trials and in clinical practice
is hand-foot syndrome (HFS), which is rarely serious
and never life-threatening (Cassidy et al., 2002).
However, HFS can significantly interfere with the
activities of normal daily living.
The aim of the current paper is to describe the
occurrence of HFS in capecitabine-treated patients, its nature, recognition, and severity, and
the role of the oncology nurse in managing HFS
optimally.
HFS, which is also known as palmar-plantar
erythrodysesthesia (or PPE), was first described in
the literature in 1974 in patients receiving mitotane therapy for hypernephroma (Burgdorf et al.,
1982; Baack and Burgdorf, 1991; Nagore et al.,
2000). In the early 1980s, it was referred to as
chemotherapy-induced acral erythema, and appeared to be associated with continuous exposure
to various chemotherapy drugs (Baack and Burgdorf, 1991).
Description/classification
In early reports, acral erythema was characterised
by erythema, numbness, tingling, dysesthesia,
and/or paraesthesia on the palms or soles; the
condition can also rarely affect the trunk, neck,
chest, scalp, and extremities (Baack and Burgdorf,
1991). In advanced cases, patients experience pain
with swelling of the skin, and even desquamation,
ulceration or blistering.
HFS has been defined more recently as a distinct
and specific presentation (Nagore et al., 2000).
Most patients present with dysesthesia, usually
with a tingling sensation of the palms and soles,
which can progress in 3–4 days to burning pain plus
well-defined symmetric swelling and erythema
(Fig. 1a). The hands tend to be more commonly
affected than the feet, and might even be the only
area affected in some patients. Erythema is
uncommon outside these areas, although occasionally a mild erythema or morbiliform eruption on the
trunk, neck, chest and extremities can accompany
the acral response (Baack and Burgdorf, 1991; Kroll
et al., 1989). Blistering and desquamation (shedding of scales or small sheets of skin) may also
ARTICLE IN PRESS
Management of hand-foot syndrome
S33
a protocol-specific, 3-grade system has generally
been applied (Blum et al., 1999), which is a
practical guide in clinical practice for dose reduction/interruption of capecitabine (Table 1).
Mechanism of HFS
Figure 1 Appearance of HFS. (a) Characteristic erythema
associated with moderate HFS. (b) Without appropriate
management, HFS can progress to an extremely painful
and debilitating condition
develop, particularly when the causative agent is
not promptly discontinued.
Dose reduction or discontinuation of the causative agent usually leads to a rapid reversal of signs
and symptoms without long-term consequences.
Nevertheless, HFS can interfere with the general
activities of daily living, especially when blistering,
moist desquamation, severe pain or ulceration
occurs (Jucgla and Sais, 1997). Without prompt
management, HFS can progress to an extremely
painful and debilitating condition (Fig. 1b).
Although HFS is not life threatening, as a cutaneous
condition affecting the hands and feet, it can cause
significant discomfort and impairment of function,
potentially leading to worsened quality of life in
patients receiving cytotoxic chemotherapy.
Different systems have been used for the
classification of HFS. The National Cancer Institute
(NCI) has a general 3-grade classification system
(Table 1). There are no grade 4 events in this HFS
classification. There is also a World Health Organisation (WHO) classification system based on 4
grades (Table 1). In clinical trials of capecitabine
5-FU was the first agent to be consistently
identified as a causative agent for HFS (Lokich
and Moore, 1984) and, until the 1990s, was the
agent most frequently associated with HFS, particularly when administered by continuous infusion
(Bellmunt et al., 1988; Fabian et al., 1990; Leo et
al., 1994; Ng et al., 1994). More recently, HFS has
become recognised as one of the most common
adverse events with capecitabine.
The mechanism of HFS is unclear. In patients
receiving 5-FU, HFS is dose-dependent and probably related to drug accumulation in the skin
(Bellmunt et al., 1988; Leo et al., 1994), possibly
of 5-FU metabolites (Diasio, 1998). Interestingly,
HFS induced by 5-FU appears to be more common in
elderly female patients (Meta-Analysis Group in
Cancer, 1998), although no such age or gender
association has been observed with capecitabine
(Abushullaih et al., 2002; Cassidy et al., 2002).
Neither the frequency nor severity of HFS appears
to correlate with plasma concentrations of various
capecitabine metabolites (Cassidy et al., 2002;
Gieschke et al., 2002, 2003).
One theory relating to capecitabine-associated
HFS is that specialised skin cells (keratinocytes)
might have upgraded levels of the enzyme thymidine phosphorylase (Asgari et al., 1999), which
could be a cause of capecitabine metabolite
accumulation, and hence result in an increased
likelihood of developing HFS. Another theory is that
capecitabine may be eliminated by the eccrine
system (sweat secretion), resulting in HFS caused
by an unknown mechanism relating to the increased
number of eccrine glands on the hands and feet
(Mrozek-Orlowski et al., 1999). HFS may also result
from increased vascularisation and increased pressure and temperature in the hands and feet. In
addition, long-term alcohol intake and strenuous
physical activity may increase the likelihood of
developing HFS.
When examined under the microscope, tissues
affected by HFS show general inflammatory
changes, dilated blood vessels, oedema and white
blood cell infiltration, although nothing really
stands out as a clear marker for the condition
(Abushullaih et al., 2002; Nagore et al., 2000).
Consequently, there is no ideal diagnosis for HFS. In
addition, HFS appears to differ according to the
ARTICLE IN PRESS
S34
Y. Lassere, P. Hoff
Table 1 HFS grading according to National Cancer Institute (NCI) (Nagore et al., 2000), World Health
Organisation (WHO) criteria (Nagore et al., 2000), and as used in capecitabine clinical trials (Blum et al., 1999).
NCI grade
NCI definition
1
2
3
Skin changes or dermatitis without pain, e.g. erythema, peeling
Skin changes with pain, not interfering with function
Skin changes with pain interfering with function
WHO
grade
WHO definition
Clinical lesion
Histological findings
1
Dysesthesia/paraesthesia, tingling in
the hands and feet
Discomfort in holding objects and upon
walking, painless swelling or erythema
Painful erythema and swelling of palms
and soles, periungual erythema and
swelling
Desquamation, ulceration, blistering,
severe pain
Erythema
Dilated blood vessels of the
superficial dermal plexus
2
3
4
1+oedema
2+fissuration
Isolated necrotic keratinocytes in
higher layer of the epidermis
3+blister
Complete epidermal necrosis
Clinical
trial
grade*
Clinical domain
Functional domain
1
Numbness, dysesthesia/paraesthesia,
tingling, painless swelling or erythema
Painful erythema, with swelling
Moist desquamation, ulceration,
blistering, severe pain
Discomfort that does not disrupt normal activities
2
3
*
Discomfort that affects activities of daily living
Severe discomfort, unable to work or perform
activities of daily living
Note: Grade to correspond to high intensity on either clinical or functional domain.
type of cytotoxic agent used. High rates of severe
HFS have been reported with pegylated liposomal
doxorubicin (D’Agostino et al., 2003), and the
condition appears to be more common and severe
(including infection and septicaemia) than in
patients receiving capecitabine.
Frequency of HFS with capecitabine
HFS (all grades) occurred in approximately 50% of
patients in early phase II studies of capecitabine
single-agent therapy in metastatic breast cancer
(MBC) (Blum et al., 1999) and metastatic colorectal
cancer (MCRC) (Abushullaih et al., 2002; Van
Cutsem et al., 2000), with 10% of patients
experiencing severe (grade 3) HFS. A higher rate
of severe HFS (52%, 12/23 cases) was reported in a
Korean study of capecitabine in combination with
docetaxel (Park et al., 2003), although this may be
related to the ability of docetaxel to cause both
HFS and nail toxicity.
Because HFS is subjectively reported, standardisation is a challenge and cross-study comparison is
difficult. A reliable appraisal of the frequency and
severity of HFS has been obtained in phase III trials
of capecitabine because of the larger numbers of
patients enrolled.
Colorectal cancer
As discussed in the previous two articles in this
Supplement, capecitabine has demonstrated a
superior safety profile compared with 5-FU/LV in
phase III trials of patients with MCRC (Cassidy et al.,
2002); HFS was the only side effect occurring
significantly more frequently on capecitabine (54%
vs. 6%) with grade 3 HFS affecting only 17% of
capecitabine-treated patients (Table 2). In addition, the lower dose of capecitabine used in
combinations with oxaliplatin (XELOX/CAPOX) or
irinotecan (XELIRI/CAPIRI) appears to result in a
reduced rate of HFS compared with single-agent
therapy (Cassidy et al., 2004a; Patt et al., 2004).
Breast cancer
In a large phase III trial comparing capecitabine in
combination with i.v. docetaxel vs. i.v. docetaxel
alone, the capecitabine/docetaxel combination
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Management of hand-foot syndrome
S35
Table 2 Frequency of HFS (all grades and grade 3) with oral capecitabine vs. i.v. comparators in large phase II/
phase III trials.
Capecitabine
HFS (%)
Comparator
All grade Grade 3 All grade Grade 3
Colorectal cancer
Capecitabine single-agent vs. 5-FU/LV (Cassidy et al., 2002)
XELOX (Cassidy et al., 2004a) vs. FOLFOX-4 (de Gramont et al., 2000)
XELIRI (Patt et al., 2004) vs. FOLFIRI (Douillard et al., 2000)
CAPOX vs. FUFOX (Arkenau et al., 2004)
Breast cancer
Capecitabine+docetaxel vs. docetaxel (O’Shaughnessy et al., 2002)
54
36
41
30
17
3
6
1
6
29
17
27
1
0
0
0
64
24
8
1
CAPOX=oxaliplatin on days 1&8+capecitabine on days 1–14, every 3 weeks; FOLFIRI=irinotecan on day 1+bolus 5-FU/LV, followed
by 5-FU (22-hour infusions) on days 1&2, every 2 weeks; FOLFOX=oxaliplatin on day 1+bolus 5-FU/LV, followed by 5-FU (22-hour
infusions) on days 1&2, every 2 weeks; FUFOX=oxaliplatin+bolus 5-FU/LV on days 1, 8, 15 and 22, every 5 weeks;
XELIRI=irinotecan on day 1+capecitabine on days 1–14, every 3 weeks; XELOX=oxaliplatin on day 1+capecitabine on days 1–14,
every 3 weeks.
was generally as well tolerated as docetaxel singleagent therapy, with HFS being the only notable
exception (O’Shaughnessy et al., 2002). The overall
rate of HFS was 64% in patients receiving capecitabine/docetaxel, with 24% of patients experiencing grade 3 HFS (Table 2). These rates of HFS are
similar to those previously noted during capecitabine single-agent therapy in patients with other
solid tumour types.
Therefore, although the overall tolerability of
oral capecitabine was good, the majority of
patients developed HFS, which was severe in
17–24% of patients. It is important that the
syndrome is well managed to prevent progression
to a more severe grade of HFS, to avoid capecitabine dose reductions and to limit the need for
discontinuation of capecitabine therapy.
Management of HFS
Dose interruption followed, if necessary, by dose
reduction should be the mainstay of HFS management. Reducing the capecitabine dose without
interruption at the first signs of HFS is likely to
result in progression of the syndrome. To deliver
capecitabine therapy as effectively as possible
requires that patients become active, educated
participants in their own treatment, and that side
effects be prevented, recognised and managed
adeptly (Gerbrecht, 2003). An example of managing a patient with MCRC who develops HFS while
receiving capecitabine is shown in Fig. 2.
Patients should, therefore, be made aware of the
first signs and symptoms of HFS and instructed,
upon development of grade 2 or 3 symptoms, to
interrupt treatment until improved to grade 0 or 1.
Treatment can be re-initiated at that time, providing that the patient is not beyond day 14 of the
cycle, in which case dosing would resume after the
scheduled 7-day rest period. If the symptoms
persist or appear during the rest period, dosing
for the next cycle is delayed until symptoms have
resolved to grade 0 or 1. Doses are adjusted as
directed in the capecitabine package insert.
While HFS is manageable, if left untreated it can
progress rapidly. Reacting quickly to the signs and
symptoms of HFS should prevent development of
grade 2/3 symptoms and, therefore, reduce the
impact on dose intensity. Nurses play a key role in
educating the patient how to recognise HFS, when
to interrupt treatment and giving instructions on
adjusting the dose to maintain effective therapy
with capecitabine over the long term. It is
particularly important that patients and nurses
are fully aware that dose interruption/reduction
does not affect the overall antitumour efficacy of
capecitabine (Cassidy and Twelves, 2000; Cassidy et
al., 2002).
Dose reduction after interruption of therapy
Discontinuation of capecitabine usually leads to
recovery over several days/weeks, depending on
severity (Abushullaih et al., 2002). Following
discontinuation, the guidelines for dose reduction
should be the same as those applied to the general
management of any adverse events occurring
during capecitabine therapy (Table 3) and provided
in the package insert. HFS tends to resolve rapidly,
often without recurrence, but if it does recur and
the patient is still benefiting from therapy, the
physician may decide to change the treatment
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S36
Y. Lassere, P. Hoff
55-year old woman with MCRC
Initiate treatment with oral capecitabine
(1250 mg/m2 twice daily on days 1–14, every 3 weeks)
1st episode of grade 3 HFS OR
2nd episode of grade 2 HFS
1st episode of grade 2 HFS
Interrupt capecitabine treatment
Maintain
Interrupt capecitabine treatment
Maintain
interruption
interruption
Does HFS resolve to grade 0/1?
Does HFS resolve to grade 0/1?
NO
NO
YES
YES
Reintroduce capecitabine
Reintroduce capecitabine
at 1250 mg/m twice daily
at 1000 mg/m twice daily
2nd episode of grade 3 HFS
OR 3rd episode of grade 2 HFS
Discontinue drug permanently
Interrupt capecitabine treatment
OR
Interrupt until resolved to grade 0/1
(at the discretion of the clinician)
Maintain
interruption
Does HFS resolve to grade 0/1?
NO
YES
1st episode of grade 4 HFS OR
Reintroduce capecitabine
3rd episode of grade 3 HFS
at 625 mg/m twice daily
Figure 2 Example of managing a patient with MCRC who develops HFS during treatment with capecitabine single-agent
therapy.
Table 3
Capecitabine dose-modification scheme for all adverse events.
NCI-CTC toxicity
grade
Appearance of
toxicity
Adjustment during therapy
Adjustment for
next cycle
(relative to
initial dose)
2
1st
2nd
3rd
4th
Interrupt until resolved to grade 0/1
Interrupt until resolved to grade 0/1
Interrupt until resolved to grade 0/1
Discontinue drug permanently
100%
75%
50%
3
1st
2nd
3rd
Interrupt until resolved to grade 0/1
Interrupt until resolved to grade 0/1
Discontinue drug permanently
75%
50%
4a
1st
Discontinue drug permanently or interrupt until
resolved to grade 0/1b
50%
NCI-CTC, National Cancer Institute Common Toxicity Criteria.
a
Not applicable to HFS.
b
At discretion of the clinician.
cycle. An example would be increasing the interval
between cycles to 2 weeks or changing the cycle
length (e.g. 10 days on, 11 days off).
When the guidelines for dose interruption and
dose reduction are followed, hospitalisations are
rare. In a recently presented study of capecitabine
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Management of hand-foot syndrome
vs. 5-FU/LV (Mayo Regimen) as adjuvant therapy for
patients with Dukes’ C colon cancer, only two
capecitabine-treated patients required hospitalisation (for 1 day) (Cassidy et al., 2004b;
Scheithauer et al., 2003).
Supportive measures
There are few supportive measures that have
proven effectiveness in controlling symptoms. Use
of topical emollients and creams would appear to
be a prudent prophylactic and symptomatic treatment at the first signs of grade 1 HFS (Gerbrecht,
2003). Regular use of a topical petroleum-lanolin
based ointment with antiseptic hydroxyquinoline
sulphate applied 3-times daily has been reported to
alleviate the symptoms of HFS induced by various
chemotherapeutic agents (including capecitabine)
(Chin et al., 2001). It should be noted that,
anecdotally, some people are allergic to lanolinbased products. Nevertheless, dose interruption
and, if necessary, dose reduction should remain the
primary tool in HFS management.
As a general recommendation, symptoms can
often be relieved by:
immersing the hands and feet in cool water
avoiding extremes of temperature, pressure, and
friction on the skin
cushioning sore skin with soft pads
topical wound care and consultation with a
dermatologist for any blistering or ulceration
(Gerbrecht, 2003).
S37
et al., 1989, 1993). One study in dogs showed that
prophylactic pyridoxine significantly delayed the
onset and severity of HFS induced by liposomal
pegylated doxorubicin, allowing a higher cumulative dose to be delivered (Vail et al., 1998). As
pyridoxine is a safe nutritional supplement, its
prophylactic use might appear appealing, although
efficacy needs to be proven prospectively in
controlled trials before routine treatment can be
recommended. Such studies need to confirm no
effect on capecitabine efficacy and whether effective prophylaxis might permit administration of a
higher cumulative dose of capecitabine.
An interesting adjunctive treatment with capecitabine might be concurrent use of celecoxib, a
COX-2 antagonist used incidentally for control of
pain and arthritis. In a retrospective series of 67
patients receiving capecitabine, the addition of
celecoxib appeared to reduce the rate of
HFS4grade 1 (from 34% with capecitabine alone
to 13% with capecitabine plus celecoxib), as
well as diarrhoea4grade 2 (from 29% to 3%) (Lin
et al., 2002). However, in this series, most patients
required dose reductions. This retrospective
study has generated a hypothesis that needs to
be tested in a prospective randomised setting.
Until then, there is insufficient evidence to
recommend the use of celecoxib in the prophylaxis
of HFS.
Conclusions
Topical (Esteve et al., 1995; Gordon et al., 1995;
Komamura et al., 1995; Vakalis et al., 1998; Vukelja
et al., 1989) or systemic (Brown et al., 1991; Esteve
et al., 1995; Hellier et al., 1996; Hoff et al., 1998;
Titgan, 1997) corticosteroids have been reported to
be useful for prophylaxis and treatment of HFS
induced by a range of different drugs, although
their use in capecitabine-associated HFS is unproven. While steroids are capable of reducing
inflammation, their long-term use can lead to
thinning of the skin, which is likely to cause
more symptoms. Diemethysulfoxide 99% 4-times
daily has been reported to be of benefit in
patients receiving liposomal doxorubicin (Lopez et
al., 1999) but is again unproven with capecitabineinduced HFS.
The use of pyridoxine (vitamin B6), at a highly
variable dose, has been anecdotally reported to be
useful for prophylaxis and treatment of HFS
induced by various agents, e.g. capecitabine, 5FU, docetaxel (Andres et al., 2003; Beveridge et
al., 1990; Fabian et al., 1990; Lauman and
Mortimer, 2001; Van Cutsem et al., 2000; Vukelja
While HFS is a common and inconvenient side effect
with capecitabine, the condition is easily managed
with dose interruption and, if necessary, dose
reductions. Prompt intervention means that patients do not need to interrupt treatment for long
periods and can, therefore, continue to benefit
from capecitabine therapy.
Oncology nurses, through patient education and
close clinical assessment, play a crucial role in the
early identification and prevention of progressive
pain, loss of the skin’s integrity, and disability. In
addition, once HFS is identified, the nurses’ role in
patient education, support, and symptom management is essential to maintain effective patient care
and, in some cases, the patient’s willingness to
continue therapy. Table 4 summarises some of the
key preventative and management techniques
for HFS.
Patient education needs to highlight the need for
reporting side effects and interrupting therapy
when required. Written materials should be provided for the patient to reinforce the teaching
ARTICLE IN PRESS
S38
Table 4
Y. Lassere, P. Hoff
Summary of preventative and management techniques for HFS.
1
Ensure patient is able to recognise HFS (and other adverse events) by education and use of written
information available from the manufacturer or otherwise.
2
Recommend preventative emollient use (e.g. hand cream).
3
Ensure that the patient follows dose interruption/reduction guidelines carefully, which apply to all
adverse events. Make sure the patient understands the importance of this prior to starting treatment
and has written information available from the manufacturer or otherwise.
4
Ensure the patient has telephone access to a key person, e.g. oncology nurse, during office hours in the
event of need to answer questions or concerns.
5
Follow up with the patient (by phone) to determine the outcome of HFS and provide other supportive
advice.
6
Reassure the patient that there are no permanent complications once adverse events have resolved.
7
Advise patients to use topical emollients and creams to keep the skin moist.
8
Recommend patients to avoid extremes in temperature, pressure, and friction of skin.
9
Mention that relief can be achieved by submerging hands and feet in cool water.
10
Suggest cushioning sore skin with soft pads or socks and keeping the skin exposed to air whenever
possible to prevent excess sweating.
11
Refer patients to a dermatologist if blistering or ulceration occurs.
12
As a last resort, if treatment is of benefit, change the dosing regimen.
13
Discontinue treatment if HFS is severe and unresolved by dose interruption/reduction.
completed at clinic visits. These materials should
incorporate:
1. Instructions on dosing, including how many
tablets to take with each dose and information
on the timing and importance of fluid intake
with medication.
2. A diary or calendar to track dosing and side
effects.
3. Reminders stressing the importance of calling
promptly and interrupting treatment at the first
signs of grade 2 toxicity.
4. Contact numbers for oncology nurses and physicians.
These materials should be accompanied by
weekly follow-up phone calls for the first few
weeks of therapy to ensure that patients fully
understand their role in reporting side effects and
withholding therapy, as instructed.
In conclusion, the nurses’ role in managing HFS in
capecitabine-treated patients is pivotal for both its
prevention and palliation.
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