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An Interdisciplinary Consensus on Managing
Skin Reactions Associated With Human
Epidermal Growth Factor Receptor Inhibitors
Beth Eaby, MSN, CRNP, OCN®, Ann Culkin, RN, OCN®, and Mario E. Lacouture, MD
The use of human epidermal growth factor receptor (HER1/EGFR) inhibitors, such as erlotinib, cetuximab, and panitumumab,
often is accompanied by the development of a characteristic spectrum of skin toxicities. Although these toxicities rarely are life
threatening, they can cause physical and emotional distress for patients and caregivers. As a result, practitioners often withdraw
the drug, potentially depriving patients of a beneficial clinical outcome. These reactions do not necessarily require any alteration
in HER1/EGFR-inhibitor treatment and often are best addressed through symptomatic treatment. Although the evidence for
using such therapies is limited, an interdisciplinary HER1/EGFR-inhibitor dermatologic toxicity forum was held in October 2006
to discuss the underlying mechanisms of these toxicities and evaluate commonly used therapeutic interventions. The result was
a proposal for a simple, three-tiered grading system for skin toxicities related to HER1/EGFR inhibitors to be used in therapeutic
decision making and as a framework for building a stepwise approach to intervention.
T
he use of HER1/EGFR-targeted therapies, such as erlotinib (Tarceva®, OSI Pharmaceuticals, Inc.), cetuximab
(Erbitux®, Bristol-Myers Squibb), and panitumumab
(VectibixTM, Amgen Inc.), often is accompanied by
the development of a characteristic spectrum of skin
toxicities (Rhee, Oishi, Garey, & Kim, 2005). Although these
events rarely are life threatening, they can cause physical and
emotional distress for patients and caregivers. Often, the rash
may be mistaken as an uncontrollable adverse effect rather than a
treatable side effect. As a result, practitioners withdraw the drug,
potentially depriving patients of a beneficial clinical outcome.
Oncology nurses often are the first point of contact for patients
who are receiving treatment; therefore, understanding the clinical
basis for such skin reactions and offering effective and appropriate
assessments and interventions are critical.
On October 29, 2006, an interdisciplinary forum was held in
Chicago, IL, to discuss skin toxicities associated with HER1/EGFRtargeted therapies. Oncologists, dermatologists, pharmacists, and
nurses shared their knowledge on the underlying mechanisms
of these events and evaluated existing practices in the hope of
reaching a consensus strategy on how best to manage them. This
article provides an overview of their discussions.
Human Epidermal Growth Factor
Receptor–Targeted Therapies
As a result of an increased understanding of the underlying molecular causes of cancer, biologic targeted agents have
At a Glance

The use of human epidermal growth factor receptor (HER1/
EGFR) inhibitors often is accompanied by the development
of a characteristic class-specific spectrum of skin toxicities.
Skin toxicities related to HER1/EGFR inhibitors do not necessar
ily require alteration in HER1/EGFR-inhibitor treatment and often are addressed best through symptomatic management.
Evidence-based treatment recommendations for skin tox
icities related to HER1/EGFR inhibitors are not available
because no data from controlled clinical studies have been
published.
Beth Eaby, MSN, CRNP, OCN®, is a nurse practitioner at the University of
Pennsylvania in Philadelphia; Ann Culkin, RN, OCN®, is a clinical nurse at
Memorial Sloan-Kettering Cancer Center in New York, NY; and Mario E.
Lacouture, MD, is a dermatologist in the Department of Dermatology at
SERIES Clinic and the Robert H. Lurie Comprehensive Cancer Center at
Northwestern University in Chicago, IL. Eaby is a member of the Tarceva®
speakers bureau and Culkin is a member of the Advisory Board and speakers bureau, both for Genentech. Lacouture received an honorarium from
Genentech and is a speaker for Genentech, ImClone, and OSI Pharmaceuticals. Mention of specific products and opinions related to those products
do not indicate or imply endosement by the Clinical Journal of Oncology
Nursing or the Oncology Nursing Society. (Submitted July 2007. Accepted
for publication September 1, 2007.)
Clinical Journal of Oncology Nursing • Volume 12, Number 2 • Managing Skin Reactions
Digital Object Identifier:10.1188/08.CJON.283-290
283
emerged since the mid-1990s as a new strategy in the treatment of various malignancies. These targeted agents interact
with specific molecules that are pivotal in tumor growth and
development. Traditional “cytotoxic” chemotherapies not
only kill tumor cells by affecting processes that commonly are
overactive or enhanced in cancerous tissue but also may be
important in affecting normal cells. Targeted agents can exert
their influence by, among other things, inhibiting tumor-cell
proliferation, inducing programmed cell death, inhibiting
angiogenesis, and enhancing antitumor immune responses
(Hoang & Schiller, 2002). Common targets for these agents
include growth factors such as the vascular endothelial growth
factor (VEGF); intracellular signaling molecules, including
cyclooxygenase-2 and the BCR-ABL tyrosine kinase; and cellsurface receptors (e.g., members of the HER family, which
includes HER1/EGFR).
The HER1/EGFR is an attractive target for new biologic
targeted agents because it has been implicated in the development of a range of tumor types (Greatens et al., 1998; Ohsaki
et al., 2000; Salomon, Brandt, Ciardiello, & Normanno, 1995).
Overexpression of the receptor also has been correlated with
disease progression, poor prognosis, and a reduced sensitivity
to chemotherapy (Cooke, Reeves, Lannigan, & Stanton, 2001;
Nicholson, Gee, & Harper, 2001). Several HER1/EGFR inhibitors
are in clinical development, and three (erlotinib, cetuximab,
and panitumumab) have demonstrated efficacy in a range of
indications and received U.S. Food and Drug Administration
(FDA) approval. Erlotinib is an oral, reversible, tyrosine kinase
inhibitor (TKI), whereas cetuximab and panitumumab are IV
administered anti-HER1/EGFR monoclonal antibodies (MAbs).
MAbs prevent ligands, such as the EGF, from binding to the
receptor, whereas TKIs block the activity of the receptor’s
tyrosine kinase (Yarden & Sliwkowski, 2001). Both prevent
the initiation of cell-signaling pathways that normally promote
tumor-cell proliferation, migration, adhesion and angiogenesis,
and inhibit apoptosis (Arteaga, 2001). A fourth agent, the TKI
gefitinib (Iressa®, AstraZeneca Pharmaceuticals), initially was
approved in patients with non-small cell lung cancer (NSCLC)
for third-line use, based on the results of a randomized phase II
trial (Kris et al., 2003). However, data from a phase III confirmatory trial failed to show a survival benefit and its use now is
restricted to patients currently or previously benefiting from it
or to patients enrolled in a clinical study (FDA, 2005).
Skin Reactions Associated
With Human Epidermal Growth Factor
Receptor–Targeted Therapies
Largely because of their specificity of action, biologic targeted
agents often are considered to have a more favorable toxicity profile than traditional chemotherapy. This also is true for
HER1/EGFR-targeted therapies, which generally are associated
with fewer hematologic adverse events than chemotherapy.
However, patients treated with HER1/EGFR-targeted therapies
often do present with a unique group of skin reactions (Rhee et
al., 2005), which occur in more than 50% of patients receiving
these treatments (Segaert & Van Cutsem, 2005).
Clinical trials with HER1/EGFR-targeted inhibitors have
revealed a spectrum of skin toxicities of varying severity (see
Table 1 and Figure 1). The most commonly reported reactions
are mild-to-moderate skin rashes that occur most frequently
on the face and upper trunk. Other common dermatologic
reactions include xerosis (dry skin), pruritus, nail changes
Table 1. Spectrum of Dermatologic Reactions Associated With Human Epidermal Growth Factor Receptor
Inhibitors
Adverse event
Description
Frequency (%)
Time Course
Rash (follicular-pustular)
Monomorphous erythematous maculopapular, follicular,
or pustular lesions, which may be associated with mild
pruritus
60–80
Onset: one to three weeks of treatment;
maximum: three to five weeks of treatment;
resolution: within four weeks of treatment
cessation but may wax and wane
Paronychia and fissuring
Painful periungual granulation-type or friable pyogenic
granuloma-like changes associated with erythema,
swelling and fissuring of lateral nailfolds, and/or distal
finger tufts
16–25
Onset: after two to four months of treatment; resolution: persistent, several months
after withdrawal
Hair changes
Curlier, finer, and more brittle hair on scalp and extremities; also extensive growth and curling of eyelashes and
eyebrows
15–6
Variable onset: after 7–10 weeks to many
months
Dry skin
Diffuse fine scaling
14–35
Occurs after appearance of rash
Hypersensitivity reactions
Flushing, urticaria, and anaphylaxis
12–3
Occurs on the first day of initial dosing
Mucositis
Mild to moderate mucositis, stomatitis, aphthous ulcers
12–36
Onset during treatment, not related to dose or
schedule; resolution without specific measures
Note. From “Epidermal Growth Factor Receptor Inhibitor–Associated Cutaneous Toxicities: An Evolving Paradigm in Clinical Management,” by T.J. Lynch, Jr., E.S.
Kim, B. Eaby, J. Garey, D.P. West, and M.E. Lacouture, 2007, Oncologist, 12(5), p. 614. Copyright 2007 by AlphaMed Press. Reprinted with permission.
284
April 2008 • Volume 12, Number 2 • Clinical Journal of Oncology Nursing
Severity
To view this image,
please see the print version.
Figure 1. Dermatologic Toxicities Secondary
to Human Epidermal Growth Factor Receptor
Inhibitors
Note. From “Mechanisms of Cutaneous Toxicities to EGFR Inhibitors,”
by M.E. Lacouture, 2006, Nature Reviews Cancer, 61(1), p. 804. Copyright 2006 by Nature Publishing Group. Reprinted with permission.
(usually manifested as paronychia), and hair changes (usually
manifested as mild hair loss) (Lacouture, 2006; Segaert & Van
Cutsem, 2005). These adverse events are observed during
treatment with all HER1/EGFR-targeted agents, MAbs, and
TKIs, and their etiology suggests that such skin toxicities are
a class effect of HER1/EGFR-targeted therapies. However, differences may exist in the incidence and manifestation of these
events with different treatments.
The papulopustular rash generally develops along a characteristic course. Within the first week, patients experience
a sensory disturbance on the face with erythema and edema,
followed by a papulopustular eruption (in weeks 1–3). In
week 4, a crusting of the rash develops. Provided that the rash
is treated successfully, patients may continue to experience
erythema and dry skin in the areas previously affected by the
papulopustular eruption.
Incidence
Directly comparing the incidence of skin toxicities (and, in
particular, rash) for different agents is challenging. Descriptive
terms often differ in gradation schemes between trials, and in
some instances skin toxicities are recorded as a single event
(e.g., dermatitis), whereas in others, they may be broken down
into separate categories (e.g., rash, acne, dry skin).
The severity of rash also appears to vary between agents. In
general, rash associated with the use of anti-HER1/EGFR MAbs
tends to be more severe than that observed with TKIs, presenting as a more purulent and pustular reaction, which may require
more aggressive interventions (Sipples, 2006).
The different modes of administration for these agents might
be one reason: TKIs (e.g., erlotinib, gefitinib) are administered
orally on a daily basis, whereas MAbs (e.g., cetuximab, panitmumumab) are given intravenously once a week or every two
weeks. The pharmacokinetic properties of these agents are
therefore different, with potentially greater differences in peak
and trough concentrations for MAbs than for TKIs. This may explain the differing incidence and manifestation of rash observed
with these agents, particularly because preclinical data support
a correlation between the appearance of rash and concentration
for these agents (Bruno, Mass, Jones, Lu, & Winer, 2003).
Some evidence suggests that the appearance of skin rash may
be useful as a marker of efficacy for HER1/EGFR-targeted agents.
Several studies with erlotinib have demonstrated a relationship
between severity of skin reaction and treatment efficacy. Phase II
studies in NSCLC, head and neck cancer, and ovarian cancer suggest that survival rates are significantly increased in patients with
skin reactions, compared to those without (Clark, Perez-Soler,
Siu, Gordon, & Santabarbara, 2003; Perez-Soler et al., 2004). This
observation was repeated in the pivotal phase III trial of erlotinib
monotherapy for NSCLC, in which the patients who developed
a rash (75%) survived significantly longer than those who did
not: 8.5 months for patients with grade 1 rash and 19.6 months
for patients with grade 2 or 3 rash versus 1.5 months for patients
who did not develop any rash (p < 0.0001) (Perez-Soler, 2006).
Overall, these observations support the consensus that patients
who develop rash should be treated for the reaction while being
maintained on anti-HER1/EGFR therapy; those patients may obtain the greatest benefit from the drugs.
Pathobiology of Skin Reactions
Associated With Human Epidermal
Growth Factor Receptor Inhibitors
Although the pathobiology of HER1/EGFR-targeted inhibitorassociated skin reactions is not understood fully, drug-induced
inhibition of the HER1/EGFR is believed to affect keratinocyte
proliferation, differentiation, migration, and attachment (Jost,
Kari, & Rodeck, 2000; Woodworth et al., 2005). HER1/EGFR is
expressed in epidermal keratinocytes, sebaceous and eccrine
glands, and the epithelium of the hair follicle (Nanney, Stoscheck, King, Underwood, & Holbrook, 1990). Such expression
is particularly high in proliferating and undifferentiated keratinocytes, which commonly are found in the basal and suprabasal
layers of the epidermis, and in the outer root sheath of the hair
follicle (Fox, 2006). Inhibition of the HER1/EGFR signaling
pathway is believed to play a critical role in inflammatory cell
recruitment and subsequent cutaneous injury, which can lead
to the development of dry skin, papulopustules, and periungual
inflammation (Lacouture, 2006). The potential effects of HER1/
EGFR inhibition in the skin are illustrated in Figure 2.
Clinical Journal of Oncology Nursing • Volume 12, Number 2 • Managing Skin Reactions
285
Guidelines for the Treatment
of Skin Reactions Associated
With Human Epidermal Growth Factor
Inhibitors
To view this image,
please see the print version.
a. Normal expression of HER1/EGFR-dependent molecular markers. Before treatment, the basal layer shows expression of phosphorylated
HER1/EGFR, MAPK (mitogen-activated protein kinase) and the proliferation marker KI67, and suprabasal expression of phopsphorylated
HER1/EGFR, the cyclin-dependent-kinase inhibitor p27, KRT1 (keratin
1) and STAT3 (signal transducer and activator of transcription 3).
b. During HER1/EGFR inhibitor therapy, phosphorylated HER1/EGFR
is abolished in all epidermal cells and the expression of MAPK is
reduced. Inhibition of HER1/EGFR in basal keratinocytes leads to
growth arrest and premature differentiation, as demonstrated by
upregulated p27 KIP1, KRT1 and STAT3 in the basal layer.
c. Subsequently, the release of inflammatory cell chemoattractants
(such as CXCLs and CCLs) recruits leukocytes that release enzymes,
causing apoptosis and tissue damage, with consequent apoptotic
keratinocytes and ectatic (dilated) vessels.
d. A decrease in epidermal thickness is observed, with a thin stratum
corneum that lacks its characteristic basket weave configuration,
indicating abnormal differentiation.
Figure 2. The Effects of Human Epidermal Growth
Factor Receptor (HER1/EGFR) Inhibition in Skin
Note. From “Mechanisms of Cutaneous Toxicities to EGFR Inhibitors,”
by M.E. Lacouture, 2006, Nature Reviews Cancer, 61(1), p. 806. Copyright 2006 by Nature Publishing Group. Reprinted with permission.
286
As yet, no data from controlled clinical studies investigating
treatment options for HER1/EGFR-targeted inhibitor-associated
skin reactions have been published; therefore, no peer-reviewed,
evidence-based treatment recommendations are available. To
date, proposed treatments are based mostly on qualitative rather
than quantitative evidence (Lacouture, Basti, Patel, & Benson,
2006; Rhee et al., 2005). However, patients still require treatment
and advice for skin reactions, and in the absence of suitable clinical data, best practice offers the best treatment advice.
The aim of the forum in Chicago was to bring a number of
experts together in an attempt to amalgamate their interdisciplinary knowledge (published or otherwise) as well as to distill
the common practices employed by their institutions into a
consensus approach for the treatment of dermatologic adverse
events associated with HER1/EGFR-targeted inhibitor therapy.
Discussion at the forum focused primarily on the clinical management of cutaneous toxicities; however, the experts also
advocated a proactive approach for patients that could minimize
the occurrence and severity of toxicities.
Practical Guidelines for Patients
Two key patient education recommendations were made at the
forum: Patients should regularly use a thick, alcohol-free emollient
for dry skin (alcohol can dry the skin). A number of recommended
emollients are listed in Table 2. Application of high-sun protection
factor (≥ 15) physical sunscreen (i.e., containing zinc oxide or titanium dioxide) each morning and prior to sun exposure is recommended for all patients receiving HER1/EGFR-targeted agents.
Based on the existing literature, a range of other practical
guidelines also might be considered to help prevent rash and
other cutaneous toxicities, which include the following (Herbst, Fox, Viele, & Messner, 2006; O’Keeffe, Parrilli, & Lacouture,
2006; People Living With Cancer, 2006).
• Patients should take care to remain hydrated.
• Patients should ensure that they apply an adequate amount
of sunscreen: more than half a teaspoon of sunscreen to
each arm, the face, and neck, and a little more than one
teaspoon to the chest and abdomen, back, and each leg. The
use of a broad-brimmed hat also is advised if going outside.
• Patients should avoid long, hot showers. Instead, patients
should use lukewarm water and mild (preferably scent-free)
soap, ensuring that genital, rectal, and skin-fold areas are
cleaned thoroughly. A moisturizer should be applied within 15
minutes of showering or bathing (to prevent skin drying).
• Patients should avoid laundry detergent with strong perfumes and use only hypoallergenic makeup.
• The use of saline nasal spray followed by petroleum jelly
may reduce risk of nosebleeds.
• Patients should use personal lubricant for intercourse.
• To prevent nail problems, patients should keep finger and toenails clean and trimmed; avoid biting of nails, pushing back cuticles, tearing the skin around the nail bed, or applying artificial
nails; and avoid tight-fitting shoes. Patients also are advised to
April 2008 • Volume 12, Number 2 • Clinical Journal of Oncology Nursing
Table 2. Recommended Agents for Dry Skin,
Itching, and Sun Exposure
Condition
Dry skin
Recommended agents
Emollients
• Vanicream® (Pharmaceutical Specialties, Inc.),
Eucerin® (Beiersdorf AG), Aquaphor® (Beiersdorf
AG), Aveeno® (Johnson & Johnson Consumer Companies, Inc.), and Cutemol® (Summers Laboratories
Inc.) as needed
Exfoliants (for scaly areas)
• Ammonium lactate12% (Am-Lactin®, Upsher-Smith
Laboratories, Inc.) for body
• Urea 20%–40% cream for palms, soles, and fissures
Itching
Sun exposure
Topical agents
• Body: Sarna Ultra® (PharmaDerm) cream and Regenecare® (MPM Medical, Inc.) gel as needed
• Scalp: Fluocinonide 0.05% shampoo or clobetasol
foam daily
Oral agents
• Antihistamines (diphenhydramine 25–50 mg twice
daily and/or cetirizine 10–20 mg per day)
• Pregabalin (Lyrica®, Pfizer) 75–100 mg twice daily
• Any broad-spectrum sunscreen containing zinc oxide or titanium dioxide
wear gloves when washing dishes or using chemical cleaning agents. Hands and feet should be moisturized frequently;
petroleum jelly is particularly effective and should be applied
to the skin around the nails periodically throughout the day.
At night, applying a thick coat to hands and feet and covering
with white cotton gloves and socks may be helpful.
• If a patient develops trichomegaly (i.e., excessive eyelash
growth) or eye complaints, the eyelashes should be trimmed
and the patient should have an ophthalmologic consultation.
Most importantly, patients should be educated to call a healthcare professional as soon as they develop any symptoms of
cutaneous toxicity. Early intervention is critical in the clinical
management of these events, so an early (< 14 days from EGFRinhibitor therapy onset) follow-up is advisable.
Clinical Management
The treatment algorithm presented in Figure 3 represents the
key output from the forum. The effective treatment of skin rashes
associated with HER1/EGFR-targeted inhibitors depends largely
on accurate grading of skin reactions to allow for appropriate
intervention. The National Cancer Institute (2006) Common
Toxicity Criteria (NCI-CTC) is used most commonly to grade
adverse events in clinical trials with HER1/EGFR-targeted agents
(see Table 3); it is designed, primarily, as a surveillance tool and
is of limited use as an aid to selecting intervention. Although certain categories are relevant to events associated with HER1/EGFR
inhibitors, including rash and desquamation, they often are not
sufficiently specific. For example, within the NCI-CTC, rash severity is based on body surface area coverage; this can be misleading
because rash associated with HER1/EGFR inhibitors generally
are confined to the face and upper trunk. For the purposes of
therapeutic decision making, forum attendees felt that a simple,
more specific grading system would be the most appropriate rash
associated with HER1/EGFR-targeted inhibitors. Thus, classifying
skin reactions as mild, moderate, or severe was believed to be the
most effective system for assigning therapeutic intervention.
The following is a stepwise approach to intervention, employing the suggested three-tiered grading system developed by the
consensus group.
Mild Skin Toxicity
Mild skin toxicity (papulopustular rash) is defined as generally
localized, minimally symptomatic, with no sign of superinfection,
and no impact on daily activities. Some attendees suggested that,
in many instances, no intervention was necessary, whereas others
felt that intervention of either topical hydrocortisone (1% or 2.5%
cream) or clindamycin (1% gel) would be beneficial. Dose reduction of the HER1/EGFR-targeted agent was not recommended.
Moderate Skin Toxicity
Moderate rash is defined as papulopustules with mild pruritus
or tenderness, with minimal impact on activities of daily living
and no signs of superinfection. The suggested therapeutic intervention is hydrocortisone (2.5% cream), clindamycin (1% gel), or
pimecrolimus (Elidel®, Novartis) (1% cream), with the addition of
doxycycline (100 mg PO BID) or minocycline (100 mg PO BID)
(Micantonio et al., 2005; Molinari, De Quatrebarbes, Andre, &
Aractingi, 2005; Sapadin & Fleischmajer, 2006). Dose reduction
of the HER1/EGFR-targeted agent was not recommended.
Severe Skin Toxicity
Severe skin toxicity is defined as a rash that may be generalized
and accompanied by severe pruritus or tenderness; this level of
toxicity has a significant impact on activities of daily living and
has the potential for superinfection. The dose of the HER1/EGFR
inhibitor should be reduced (according to the principal investigator). The skin toxicity should be treated the same as for moderate
rash but with the addition of a methylprednisolone dose pack. In
the event that severe rash symptoms fail to respond to the abovementioned interventions, interruption of the HER1/EGFRI-targeted therapy is recommended. However, treatment may resume
(most likely at a lower dose) once skin reactions have diminished
in severity at a recommended follow-up of two weeks.
The use of pimecrolimus or tacrolimus (Protopic®, Astellas
Pharma, Inc.) for HER1/EGFR-associated skin reactions is being
investigated at a number of institutions; however, it is an immunosuppressant, which should be taken into account when considering treatment options (Novartis, 2006). Although a causal
relationship has not been established, rare cases of skin malignancies and lymphoma have been observed in patients treated
with calcineurin inhibitors, such as pimecrolimus (Novartis).
Such incidences most likely are associated with long-term usage;
pimecrolimus is not recommended, however, in immunosuppresed patients (Novartis). As a result, great care should be
taken when considering its use in patients with cancer.
Conclusion
The skin toxicities associated with HER1/EGFR-targeted
inhibitors can cause patients physical and psychological symp-
Clinical Journal of Oncology Nursing • Volume 12, Number 2 • Managing Skin Reactions
287
•
•
•
•
Employ a proactive approach in managing skin reactions.
Suggest patients use a thick, alcohol-free emollient cream.
Suggest patients use a sunscreen of SPF 15 or higher, preferably containing zinc oxide or titanium dioxide.
If a patient presents with rash, verify appropriate administration and follow the proceeding algorithm in a step-wise manner.
Rash Severity
Intervention
Mild
• Generally localized
• Minimally symptomatic
• No impact on ADL
• No sign of superinfection
Continue EGFR inhibitor at current dose and monitor for change in severity.
No treatment
or
Topical hydrocortisone 1% or 2.5% cream* and/or clindamycin 1% gel
Reassess after 2 weeks (either by healthcare professional or patient self-reported); if reactions
worsen or do not improve, proceed to next step.
Moderate
• Generalized
• Mild symptoms (e.g.,
pruritus, tenderness)
• Minimal impact on ADL
• No sign of superinfection
Continue EGFR inhibitor at current dose and monitor for change in severity; continue treatment of
skin reaction with the following:
Hydrocortisone 2.5% cream* or Clindamycin 1% gel or pimecrolimus 1% cream PLUS doxycycline
100 mg BID or minocycline 100 mg BID
Reassess after 2 weeks (either by healthcare professional or patient self-reported); if reactions
worsen or do not improve, proceed to next step.
Severe
• Generalized
• Severe symptoms (e.g.,
pruritus, tenderness)
• Significant impact on
ADL
• Potential for
superinfection
Reduce EGFR-inhibitor dose as per label and monitor for change in severity; continue treatment of
skin reaction with the following:
Hydrocortisone 2.5% cream* or clindamycin 1% gel or pimecrolimus 1% cream PLUS doxycycline
100 mg BID or minocycline 100 mg BID PLUS medrol dose pack
Reassess after 2 weeks; if reactions worsen, dose interruption or discontinuation may be necessary.
* The use of topical steroids should be employed in a pulse manner based on your institution’s guidelines.
ADL—activities of daily living; BID—twice daily; EGFR—epidermal growth factor receptor; SPF—sun protection factor
Figure 3. Proposed Therapy Algorithm for the Management of Skin Reaction Associated
With Human Epidermal Growth Factor Receptor Inhibitors
Note. From “Epidermal Growth Factor Receptor Inhibitor–Associated Cutaneous Toxicities: An Evolving Paradigm in Clinical Management,” by T.J. Lynch, Jr., E.S.
Kim, B. Eaby, J. Garey, D.P. West, and M.E. Lacouture,” 2007, Oncologist, 12(5), p. 618. Copyright 2007 by AlphaMed Press. Reprinted with permission.
toms, particularly given that rash characteristically occurs
on exposed areas such as the face. Although the concerns of
patients (and caregivers) must be addressed sympathetically,
in most cases, these adverse events can be managed without
the need for dose modification or interruption to the HER1/
EGFR-inhibitor regimen. Moreover, in refractory cases, the
suspension of HER1/EGFR inhibitor therapy is temporary,
allowing for appropriate intervention and diminution of skintoxicity severity.
288
The algorithm suggested by the consensus group and presented in this article represents current best practice for the
treatment of rash associated with HER1/EGFR inhibitors. Controlled studies remain necessary to fully evaluate the efficacy
of the strategies presented in the algorithm, but this approach
hopefully will be a useful guide for nurses and other healthcare
professionals, ensuring that patients receive the maximum possible clinical benefits from the continued and uninterrupted use
of the HER1/EGFR inhibitors.
April 2008 • Volume 12, Number 2 • Clinical Journal of Oncology Nursing
Table 3. Classification of Dermatologic Toxicities Associated With Human Epidermal Growth Factor
Receptor Inhibitors
Grade
Adverse event
1
2
3
4
5
Dry skin
Asymptomatic
Symptomatic, not interfering with
ADL
Interfering with ADL
–
–
Nail changes
Discoloration, ridging,
pitting
Partial or complete loss of nails;
pain in nailbed(s)
Interfering with ADL
–
–
Pruritus/itching
Mild or localized
Intense or widespread
Intense or widespread and interfering with ADL
–
–
Rash/
desquamation
Macular or papular
eruption or erythema
without associated
symptoms
Macular or papular eruption or
erythema with pruritus or other
associated symptoms; localized
desquamation or other lesions
covering < 50% BSA
Severe, generalized erythroderma or macular, papular, or
vesicular eruption; desquamation
covering > 50% BSA
Generalized exfoliative, ulcerative, or
bullous dermatitis
Death
Rash: acne/
acneform
Intervention not
indicated
Intervention indicated
Associated with pain, disfigurement, ulceration, or desquamation
–
Death
Dermatology/
skin—other
Mild
Moderate
Severe
Life threatening;
disabling
Death
ADL—activities of daily living; BSA—body surface area
Note. From Common Terminology Criteria for Adverse Events (CTCAE) [v.3.0], by National Cancer Institute, 2006. Retrieved February 20, 2008, from
http://ctep.cancer.gov/forms/CTCAEv3.pdf. Adapted with permission.
The authors gratefully the participants of the October 2006 interdisciplinary forum: Jean Pierre DeLord, Jody Gary, Giuseppe Giaccone,
Patricia LoRusso, Thomas J. Lynch, Barbara Melosky, Martin Reck,
Roman Perez-Soler, Jennifer Temel, and Dennis P. West. The authors
also acknowledge third-party medical writing support from Gardiner
Caldwell US, funded by Genentech, Inc., OSI Pharmaceuticals, Inc.,
and F. Hoffmann-La Roche Ltd.
Author Contact: Beth Eaby, MSN, CRNP, OCN®, can be reached at eabyb@
uphs.upenn.edu with copy to editor at [email protected].
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April 2008 • Volume 12, Number 2 • Clinical Journal of Oncology Nursing