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White Paper
Managing Skin Toxicities
Skin toxicities from chemotherapy and radiation in patients with cancer
A
survey by CancerCare, a leading source for
treatment-related patient information,1 confirmed
that although only two in five people with cancer
were concerned about experiencing skin-related
toxicities when they started treatment, almost 80%
were troubled by the actual skin effects they experienced during
and after treatment. The survey, conducted in early 2008, involved
345 patients who participated in a CancerCare Telephone
Education Workshop. Survey respondents reported having either
breast, ovarian, lung, colon/rectal, prostate, bladder, or kidney
cancer and were undergoing or had completed various treatment
regimens. Survey results showed that 63% of respondents agreed
with the statement: “The effect or impact on my skin was worse
than I thought.” Further, one in three respondents said the skinrelated side effects had negatively affected their lives.
Oncology nurses must be prepared to help their patients
manage skin toxicities, and an important starting point is knowing
what types of treatment cause skin-adverse events. In recent
years, perhaps the greatest attention has been focused on the
skin effects of targeted therapies, including epidermal growth
factor receptor (EGFR) inhibitors, vascular endothelial growth
factor inhibitors (VEGFR), and mammalian target of rapamycin
(mTOR) inhibitors. Agents in these categories can be either
tyrosine kinase inhibitors or monoclonal antibodies.
Rash in response to EGFR inhibitor. Photo provided by Pamela
Hallquist Viale, RN, MS, ANP, AOCNP ®.
Hand foot skin reaction, patient on capecitabine for 10 weeks.
Lucid Smog, photo in public domain.
1
Managing Skin Toxicities with Lindi Skin Products • April 2014
Table 1. Selected Targeted Agents
That May Cause Skin Effects
Agent
Axitinib2
Cabozantinib2
Cetuximab
Skin
Effect(s)
Type
Target
TKI
VEGFR 1,2,3;
PDGFR, c-kit
HFSR
TKI
VEGFR2, c-Met
HFSR
MoAB
EGFR
Rash
TKI
EGFR
Rash
Everolimus4
TKI
mTORcomplex-1
Rash
Lapatinib
TKI
EGFR
Rash
EGFR
Rash
3
Erlotinib3
3
Panitumumab3 MoAB
2,5
Pazopanib
TKI
VEGFR, PDGFR, and
c-kit tyrosine kinases
HFSR
Regorafinib2
TKI
Stromal and oncogenic
receptor tyrosine
kinase (RTK)
HFSR
Sorafenib2
TKI
ATP-competitive multitargeted kinase inhibitor
(MKI); Raf kinase, VEGFR 2-3, PGDFR-β, c-kit,
Fms-like tyrosine kinase
3 (Flt-3), and Ret
HFSR
VEGFR 1-3, PDGF
α and β, stem cell factor receptor c-kit, Flt-3,
colony-stimulating factor
receptor type 1, and Ret
HFSR
Sunitinib2
TKI
Chemotherapy of a variety of types may also cause skin-adverse
events. For example, macular-papular rashes of varying severity
have been observed in patients receiving high-dose chemotherapy
as induction, consolidation, or conditioning therapy prior to stem
cell or bone marrow transplant.8 In one study, the primary offender
was cytarabine,8 but other agents such as docetaxel, doxorubicin,
fluorouracil, cyclophosphamide, and vincristine can also cause
hyperpigmentation, photosensitivity, onycholysis (shedding of
nails), alopecia, hand foot skin reaction (HFSR), dry skin and
itching, and radiation recall and enhancement.9
Table 2. Selected Chemotherapy Agents
That May Cause Skin Effects9
Agent
Type
Skin Effect(s)
Polypeptide
antibiotic
Rash
Azathioprine
Antimetabolite
Eccrine squamous
metaplasia
Bleomycin
Glycopeptide
antibiotic
neutrophilic eccrine
hidradenitis, Hyperpigmentation, itching
Capecitabine
Antimetabolite
Eccrine squamous
metaplasia
Chlorambucil
Nitrogen mustard
Eccrine squamous
metaplasia
Cyclophosphamide
Nitrogen mustard HSFR, eccrine squamous metaplasia
Cytarabine
Nucleoside Metabolic Inhibitor
HSFR, neutrophilic
eccrine hidradenitis
Actinomycin D
Temsirolimus4
TKI
mTORcomplex-1
Rash
Dacarbazine
Alkylating agent
Photosensitivity
Vandetinib
TKI
EGFR
Rash
Daunorubicin
TKI
V600E mutated BRAF
HFSR
Anthracycline
Topoisomerase
Inhibitor
HSFR, hyperpigmentation
Taxane
HSFR, alopecia, recall
reaction, nail changes
Doxorubicin
Anthracycline
HSFR, alopecia, recall
reaction, eccrine squamous metaplasia, nail
changes
Epirubicin
Anthracycline
Alopecia, eccrine
squamous metaplasia,
nail changes
Etoposide
Topoisomerase
inhibitor
HSFR, recall reaction
Fluorouracil
Antimetabolite
HSFR, photosensitivity, eccrine squamous
metaplasia
Gemcitabine
Nucleoside Metabolic Inhibitor
Recall reaction
Hydroxyurea
Antineoplastic
Nail changes
3
Vemurafinib
2
HFSR=Hand foot skin reaction causes redness, swelling, and pain on
the hands and/or the soles of the feet, sometimes with blisters. It can
occur on other areas of the skin, such as the knees and the elbows. It
can cause discomfort, pain on grasping or using hands, and difficulty
walking.2 TKI=tyrosine kinase inhibitor; MoAB=monoclonal antibody;
VGFR=vascular endothelial growth factor receptor; PDGFR=plateletderived growth factor receptor; c-kit=gene for transmembrane kinase
related to colony-stimulating factor type 1 and PDGFR; Raf=serine/
threonine-specific protein kinase related to retroviral oncogenes; Flt3=receptor tyrosine kinase with important roles in hematopoietic stem/
progenitor cell survival and proliferation; V600E mutated BRAF=
determinant of sensitivity to proteasome inhibitors; mTOR= mammalian
target of rapamycin; EGFR=epidermal growth factor receptor.
The rash most commonly seen with EGFR inhibitors has been
variously described as macular-papular or acneiform, and it usually
affects the head and neck, face, upper chest, and upper back. It
can vary widely in severity, but severity has been associated with
drug efficacy for several agents.6 It can be potentially disfiguring
and painful, and it may lead to dose reduction or interruption. No
uniform method of assessing the EGFR-related rash has been
created, nor has a uniform technique of assessing the psychological
impact of the rash on patients. It is widely recognized that the
rash can have a profound psychological effect; some patients may
refuse to leave their homes or to participate in social activities
because of it.7
Docetaxel
2
Managing Skin Toxicities with Lindi Skin Products • April 2014
Table 2. Selected Chemotherapy Agents
That May Cause Skin Effects9 (cont.)
Agent
Type
Skin Effect(s)
Idarubicin
Anthracycline
Alopecia, eccrine
squamous metaplasia,
nail changes
Melphalan
Nitrogen mustard
Eccrine squamous
metaplasia
Thiopurine
HSFR
Methotrexate
Antimetabolite
HSFR, photosensitivity, recall reaction,
eccrine squamous
metaplasia
Mitoxantrone
Anthracycline
Alopecia
Taxane
Alopecia, nail changes
Mercaptopurine
Paclitaxel
Vinblastine
Vinca alkaloid
HSFR
Vincristine
Vinca alkaloid
HSFR
Vinorelbine
Vinca alkaloid
Hyperpigmentation
Neutrophilic eccrine hidradenitis=fever and skin eruptions. Recall
reaction= recu r rence of sy mptoms af ter sunbu r n or radiation.
Photosensitivity=increased reactivity to sun exposure. Alopecia=hair loss.
Eccrine squamous metaplasia=noninflammatory metaplasia of the cuboidal
epithelial cells of the eccrine sweat ducts. Hyperpigmentation=increase in
and darkening of skin color.10
Finally, among the most frequently seen skin effects are the
toxic results of radiation therapy. Schnur, Ouellette, DiLorenzo,
et al. found that radiation dermatitis affects multiple dimensions
of quality of life. It can cause physical discomfort, body image
disturbance, emotional distress, and impair both day-to-day
functioning and satisfaction with radiation treatment in women
with breast cancer.11 In fact, up to 90% of patients with breast
cancer or head and neck cancer who are treated with radiation may
experience radiation dermatitis.12
How can oncology nurses help their patients manage these
effects in order to maximize outcomes? Experts have developed
recommendations for the management of skin reactions, especially
those related to EGFR inhibitors. Dr. Mario Lacouture and others
published clinical practice guidelines for the prevention and
treatment of EGFR inhibitor-associated dermatologic reactions in
2011.13 In addition, the Multinational Association for Supportive
Care in Cancer (MASCC) issued a patient guide based on one
developed at Memorial Sloan Kettering Cancer Center.14 These
two statements have important commonalities. They identify
the most frequent skin effects as rash, itching, dry skin, and nail
and hair changes. For rash, they suggest antibiotics (topical and
systemic) and hydrocortizone with moisturizers and sun screen
and discourage acne medications. For dry skin, they recommend
moisturizers and sun screen. For itching, they suggest gentle skin
care, antihistamines, topical steroids, and creams with menthol.
For hair loss, if scarring, they suggest the same treatment as
for rash; if not scarring, minoxidyl may help. For paronychia,
they call for diluted bleach or vinegar soaks, mild skin care, and
corticosteroids – antibiotics may be needed in case of infection.
The one thread that runs through all the recommendations
is skin hygiene and care that includes mild cleansing agents,
moisturizers, and sun screen. Similar suggestions are made for
HSFR, including moisturizers and avoidance of harsh chemical
products, by Cancer.Net.2
Lindi Skin products
Fortunately for patients with cancer and their caregivers,
a line of skin care products has been specially created for them.
It was developed with the counsel of leading dermatologists and
oncologists for those suffering the skin side effects of specific
cancer therapies. This extensive collection of mild and luxurious
serums, lotions, and balms is the only full line of skincare
products developed to improve the lives of individuals undergoing
chemotherapy and radiation therapy. They are formulated to be
non-irritating and hypo-allergenic, and they have been laboratory
tested. In addition, an advisory panel of leading medical and
scientific experts that includes prominent oncologists helps to
insure that Lindi Skin products are safe and effective.
Oncology nurses asked Lindi Skin for evidence of the products’
effectiveness.15 The company initiated a clinical trial, conducted
at Northwestern University, in which 99 patients with cancer who
were receiving systemic anticancer therapies and/or radiation
therapy were evaluated for skin reactions. The National Cancer
Institute Common Terminology Criteria for Adverse Events
version 3.0 (NCI-CTCAE v 3.0) and the Skindex-16 self-reported
quality of life instrument were used. Each participant received three
test products and was instructed to use them once daily for four
weeks. The products included a skin moisturizer, face moisturizer,
and face wash. All were formulated based on surveys of patients
with cancer for their skin product preferences. At four weeks,
the remaining patients (n=77) were reassessed and tolerability
questionnaires were administered for each product used. Dry skin,
HFST, and rash decreased significantly from baseline to follow-up.
Participants had a significantly lower mean overall Skindex-16
score compared to baseline (16.19 vs. 25.05; p=0.0003). Most
patients rated their overall experience with the products as good
or very good. Most found the products to be better tolerated than
others previously tried and to be more soothing. Satisfaction with
the products did not vary by skin type. These findings suggested
that quality of life improved with product use, and three critical
forms of skin toxicity were decreased with the use of the products
within four weeks.16
“We started using
your face serum
[Lindi Skin] on our
daughter ’s face
(she’s a 2-yearBEFORE
AFTER
old with Acute
Lymphoblastic Leukemia) at the end of January. We had
tried numerous other things that hadn’t helped clear up
her rash. Within the first 2 weeks of using the face serum,
we watched the rash fade and nearly disappear. She
has gone from screaming and trying to hide with other
products to asking if it is time for her ‘cream that makes
my face feel better.’ It is nothing short of a miracle.”
February 2014
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Managing Skin Toxicities with Lindi Skin Products • April 2014
Lindi Skin now offers eleven products for use with sensitive or
compromised skin:
1. Cooler roll – non-adhesive dressing for post-radiation relief
2. Lavender face serum, including proprietary LSA ®
complex
3. Citrus face serum
4. Body wash
5. Soothing balm – useable on body, but particularly
for dry, cracked hands and feet
6. Face moisturizer
7. Lip balm
8. Eye hydrator gel
9. Reusable cooler pad
10. Body lotion
11. Face wash
Patients can also purchase sets of products in sample sizes or to
comprise regimens designed for radiation therapy, chemotherapy,
and combined therapy.
As word of the effectiveness and tolerability of Lindi Skin
products has spread, they have been made available in at least 100
cancer centers across the county. Genentech, GlaxoSmithKline,
and Merck included them in starter packs and as aids for patients
receiving their agents that cause skin effects.
Lindi Skin products can be ordered directly from the Lindi Skin
website, and now they are widely available in pharmacies. In 2014,
CVS joined the growing list of distributors.
For more information or to place an order,
go to: www.Lindi Skin.com.
To find a store near you and your patients,
go to: www.linkiskin.com/retail-locator.
Note: T his White Paper was prepared by ONS:Edge in collaboration
with Lindi Skin.
References
Retrieved March 31, 2014, from www.cancercare.org.
Hand-Foot Syndrome or Palmar-Plantar Erythrodysesthesia. Cancer.
Net. Retrieved April 1, 2014, from http://www.cancer.net/navigatingcancer-care/side-effects/hand-foot-syndrome-or-palmar-plantarerythrodysesthesia.
3
EGFR Inhibitors. Drugs.com. Retrieved April 1, 2014, from http://www.
drugs.com/drug-class/egfr-inhibitors.html.
4
Balagula Y, Rosen A, Tan BH, et al. Clinical and histopathologic
characteristics of rash in cancer patients treated with mammalian target
of rapamycin inhibitors. Cancer. 2012;118:5078–83.
5
Balagula Y, Wu W, Su X, et al. The risk of hand foot skin reaction to
pazopanib, a novel multikinase inhibitor: a systematic review of literature
and meta-analysis. Invest New Drugs. 2012; 30:1773–1781.
6
Ortega-Parra C, Donath E, Garcia SR, Jacobson RJ. Correlation between
development of rash and efficacy of EGFR inhibitors: a meta-regression
analysis. J Clin Oncol. 2013;31 (suppl; abstr e13539).
7
White KJ, Roydhouse JK, Scott K. Psychosocial impact of cutaneous
toxicities associated with epidermal growth factor receptor-inhibitor
treatment. Clin J Oncol Nurs. 2001;15:88-96.
8
Wright LG. Maculopapular skin rashes associated with high-dose
chemotherapy: Prevalence and risk factors. ONF. 2007;33:1095-1103.
9
Skin Toxicity of Chemotherapy Drugs. Derm Net NZ. Retrieved March
31, 2014, from http://dermnetnz.org/reactions/chemotherapy-toxicity.html.
10
Kufe DW, RE, Pollock RE Weichselbaum RR, et al., eds. Holland-Frei
Cancer Medicine. 2003: Hamilton, ON: BC Decker.
11
Schnur JB, Ouellette SC, DiLorenzo TA, et al. A qualitative analysis
of acute skin toxicity among breast cancer radiotherapy patients.
Psychooncology. 2011;20:260-268.
12
Balagula Y, Hensley JR, Gerami P, Lacouture ME. Acneiform rash as a
reaction to radiotherapy in a breast cancer patient. JSCO. 2010; 8: 268-271.
13
Lacouture ME, Anadkat MJ, Bensadoun R-J, et al., for the MASCC Skin
Toxicity Study Group. Clinical practice guidelines for the prevention and
treatment of EGFR inhibitor-associated dermatologic toxicities. Support
Care Cancer. 201;19:1079–1095.
14
Multinational Association of Supportive Care in Cancer (MASCC).
Caring for Your Skin, Hair and Nails when on “Targeted Therapies.”
Retrieved March 31, 2014, from http://www.mascc.org.
15
ONS:Edge Advisory Board, 2008.
16
Haley AC, Calahan C, Gandhi M, et al. Skin care management in cancer
patients: an evaluation of quality of life and tolerability. Support Care
Cancer. March 25, 2010: published online.
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Managing Skin Toxicities with Lindi Skin Products • April 2014