Some colorectal cancer treatments lead to side effects of the skin. In this webinar, Dr. Nicole LeBoeuf will discuss these specific side effects. She will talk about why they occur, how to prepare for them, and how to manage them.

1. OUR WEBINAR WILL BEGIN SHORTLY

2. CRC TREATMENT SIDE EFFECTS OF
THE SKIN

3. TODAY’S
WEBINAR
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QUESTIONS
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medical advice, diagnoses or treatment.
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6. TODAY’S
PRESENTER
Nicole R. LeBoeuf,
MD, MPH
Dr. LeBoeuf received her medical degree from the University of Massachusetts Medical
School in 2006. She completed her residency in Dermatology at Columbia University, where
she served as Chief Resident, followed by a fellowship in Cutaneous Oncology at Brigham and
Women’s/Dana-Farber Cancer Center at Harvard. Dr. LeBoeuf joined the faculty in the
Department of Dermatology and Center for Cutaneous Oncology at Dana-Farber and
Brigham and Women’s in 2012 and earned a Masters in Public Health from the Harvard TH
Chan School of Public Health in 2015.
In addition to directing the Cutaneous Oncology and Medical Dermatology Fellowship
programs, Dr. LeBoeuf established and directs the Program in Skin Toxicities from Anticancer
Therapies at the Dana-Farber/Brigham and Women’s Cancer Center. She is the Clinical
Director for the Center for Cutaneous Oncology, where leads clinical trials in cutaneous
lymphoma and rare skin malignancies as well as interventional studies for the prevention or
management of side effects from cancer treatment. Her research focuses on understanding
the immunologic mechanisms of side effects to cancer therapeutics and implementing
therapies or other interventions to mitigate them.

7. Skin Toxicities from Therapies Used to Treat
Colorectal Cancer
Nicole R. LeBoeuf, MD, MPH
February 11, 2020
Clinical Director, The Center for Cutaneous Oncology
Director, The Program In Skin Toxicities from Anticancer Therapies
Dana-Farber Cancer Institute/Brigham and Women’s Hospital
Harvard Medical School

8. Disclosures
Nicole R. LeBoeuf, MD, MPH
Skin Toxicities from Therapies Used to Treat Colorectal Cancer
Bayer: Speaker, Consultant
Seattle Genetics: Consultant
Sanofi: Consultant
I will discuss the off label use of topical and systemic therapies for the management of
dermatologic adverse events from cancer treatment

9. Agenda
• Introduction
• Skin Toxicities from EGFR Inhibitors
• Reactions on the Hands and Feet
• Ask questions as we go – and at the end!

11. People come into my office looking for
unconditional love or complaining that their
spouse does not offer it. Now I can tell them
they already have it.
Their epidermis caresses them, contains them,
bends anyway they like, and asks nothing in
return. Maybe we hydrate it or protect it from
the sun, but that is hardly an equal partnership.
I will never take my skin for granted again.

12. 0 20 40 60 80 100
Vandetanib
Temsirolimus
Sunitinib
Sorafenib
Regorafenib
Pertuzumab
Pazopanib
Nilotinib
Lenalidomide
Ipilimumab
Everolimus
Erlotinib
Dasatinib
Cetuximab
Cabozantinib
Axitinib
Afatinib
High Grade
All Grade
Percent of patients with dermatologic adverse event
The Scope of the Skin Toxicity Problem
Incidence of
Skin Reaction
Ramirez-Fort 2014, Gomez-Fernandez 2012, Minkis 2013, Drucker 2012, Fischer 2012, Chu 2008, Chu 2009, Balagula 2012, Nardone 2013, Lacouture 2013,
Belum 2013, Shameem 2015, Rosen 2012, Jia 2009, Su 2009, Belum 2015
Drugs used to treat CRC commonly cause
problems with the skin, hair and nails
Some drug classes cause rash in 80% of patients
– or 4 out of 5 patients treated
Some drug classes cause severe issues in 20% of
patients – or 1 in 5 patients treated

13. EGFR Inhibitor in Colorectal Cancer:
Rash is Associated with Response and Survival
Vincenzi B, et al. Br J Cancer. 2006;94:792-797; Saltz LB, et al. J Clin Oncol. 2004;22:1201-1208;
Hecht JR, et al. Cancer. 2007;110:980-988. Figure courtesy of M.E.
Lacouture
Vincenzi 2006[1]
P = .06
Saltz 2004[2]
P = .02
Hecht 2007[3]
HR: 0.72; 95% CI: 0.54-0.97
Grade 0-1
Grade 2-4
Grades 0-2
Grade 3
Grade 0
Grade 3
Median OS
(Months)
0 5 10
Cetuximab
Cetuximab
Panitumumab
RashGrade
9.1 months
10.3 months
1.9 months
9.5 months
6.1 months
10.5 months
EGFR Inhibitor rash is associated with the
therapy working better and with longer survival.
The worse the rash, the better the response to
treatment.
Treating the rash does not reverse the benefit.

14. Capecitabine-Hand Foot Syndrome in CRC
• Capecitabine-induced HFS is associated with
better survival in CRC patients
CRC, colorectal cancer; HFS, hand-foot-skin; HR, hazard ration; OS, overall survival;
PFS, progression-free survival
Hofheinz RD et al. Br J Cancer. 2012;107(10):1678-83.
PFS OS
CRC patients who get hand foot syndrome with
capecitabine, live longer.

15. Targeted Therapies and Quality of Life
• Patients on targeted therapies experience
more dermatologic side effects than those on
non-targeted therapies
• Patients with EGFRi rash suffer with more
symptoms, are affected emotionally and have
issues with daily functioning
Rosen AC et al. Am J Clin Dermatol 2013; 14:327-33.

16. Burden
Dose
Adherence
Cost
Quality of life
Prognosis
Balagula, et al. J Am Acad Dermatol. 2011 Sep;65(3):624-35
Dermatologic side effects are common in CRC
cancer treatment
They cost time and money treat
The are associated with better cancer outcomes
They affect well being, privacy and quality of life
You are not alone.
A whole subspecialty of dermatology has been
developed just for this.

17. Dana-Farber Cancer Institute/Brigham and
Women’s Hospital Skin Toxicities Team

19. Effect of EGFRi on Skin
• Hair follicle inflammation
• Dry skin
• Bacterial overgrowth
• Sensitivity to sunlight

20. Figure: LeBoeuf
Papulopustular (Acne-like) Reaction

21. Figure: LeBoeuf
Papulopustular (Acne-like) Reaction

22. Papulopustular (Acne-like) Reaction
Figure: LeBoeuf

23. Papulopustular (Acne-like) Reaction
Figure: LeBoeuf

24. Papulopustular (Acne-like) Reaction
Figure: LeBoeuf

25. Papulopustular (Acne-like) Reaction
Figure: LeBoeuf

26. Figure: LeBoeuf
Papulopustular (Acne-like) Reaction

27. Clin Colorectal Cancer. 2018 Jun;17(2):85-96.
Papulopustular (Acne-like) Reaction

28. Can I Prevent the Acne-Like Rash?
Grade ≧ 2 skin toxicities in the 6
week
treatment period was 29% vs
62% for
pre-emptive versus reactive
group
1Lacouture ME, et al. J Clin Oncol. 2010;28(8):1351-7.
Using a prevention regimen
decreased the likelihood of a
moderate rash by 33%

29. Can I prevent this rash?
• Minimize dryness
– Bathe or shower in warm, not hot, water
– Gentle cleanser, fragrance free
– Apply bland, thick moisturizer twice a day
• Broad spectrum UVA/UVB SPF 30+ at all times
• Prescription topical steroids to face, upper back and
chest twice a day
• Oral antibiotics (doxycycline or minocycline)
UVA, Ultraviolet A; UVB, ultraviolet B; SPF, sun protection factor
1Lacouture ME, et al. J Clin Oncol. 2010;28(8):1351-7.
Most of the time. If not, you can make it less severe.

30. What If I Don’t Start the Prevention Regimen?
Sheu J, et al. Clin Breast Cancer. 2015;15:e77-81.
Reacting Works Too!

31. Dry Skin and Eczema Like Rash
Figures: LeBoeuf
 Aggressive thick, bland moisturizers at least twice a day
 Topical steroids for inflammation and dermatitis

32. Skin Fissures
Figures: LeBoeuf
 High potency topical steroids for
inflammation
 Thick ointment based moisturizers
 Skin glue for fissure pain

33. Bacterial Overgrowth
Figure: LeBoeuf
 Bleach baths: ¼ cup in 40 gallon tub
 Your doctor may prescribe mupirocin (antibiotic) ointment to open or
crusted areas and inside nostrils
 You may need oral antibiotics if you are not already on them

34. Hair Changes
 May cause hair loss
 May cause hair curling
 May be brittle and dry
 Increased hair growth on
the face may occur
Figures: LeBoeuf

35. Hair Changes
 Gentle hair care
 Processing and coloring can
lead to scalp irritation or
breakage of brittle hair
 Coloring can be ok
 If your scalp is inflamed or
itchy, speak to your doctor first
Figure: LeBoeuf

36. Hair Changes
 Eflornithine is ok, but can be irritating
 Laser hair removal is ok
 Electrolysis is ok
 If you develop irritation or inflammation speak to your oncologist
or dermatologist for additional tips and tricks
Figure: LeBoeuf

37. Trichomegaly: Overgrown Eyelashes
EGFRi, EGFR inhibitor.
Figures: LeBoeuf.
 Trim lashes to prevent corneal
scratching

38. Paronychia: Inflammation Around Nails
 Your doctor may culture if there is pus
 Oral antibiotics
 Dilute vinegar soaks
 Topical high potency steroids

39. Excess Tissue Around Nails
Figure: LeBoeuf
 Treat paronychia
 Silver nitrate for granulation tissue
 Tape to pull lateral nail fold away
 Wide toe box in shoes

40. Wide Toe Box Shoes
https://www.northernrunner.com/shoes-c133/natural-or-midfoot-running-shoes-c238
https://www.somfootwear.com/blogs/news/wide-shoes-vs-wide-toe-box-what-keeps-feet-comfortable

41. Tape the skin away from the nail
https://bpac.org.nz/BPJ/2014/December/ingrown-toenails.aspx

42. Sun Sensitivity
Figure: LeBoeuf

43. • Photosensitivity:
– UVA Mediated
Sun Sensitivity
Dummer et al. NEJM. 2012. 366; 480-481
 Broad spectrum, high SPF suncreen DAILY
 Reapply every 2 hours if outdoors
 UVA penetrates window glass

44. Key Reminders
When Starting and EGFR Inhibitor:
• Bathe or shower in lukewarm or cool water
• Topical steroid daily to face, chest upper back
• Broad spectrum UVA/UVB SPF 30+ at all times
• Bland thick moisturizer (ointment or cream)
• Consider oral antibiotics (Minocycline or
Doxycycline)
UVA, Ultraviolet A; UVB, ultraviolet B; SPF, sun protection factor

46. NOT ALL REACTIONS ON THE HANDS AND FEET ARE THE
SAME
Reactions on the Hands and Feet
Figures: LeBoeuf

47. NOT ALL REACTIONS ON THE HANDS AND FEET ARE THE
SAME
Reactions on the Hands and Feet
• Dorsal hand-foot syndrome
– Taxanes
• Hand-foot syndrome/Palmoplantar erythrodysesthesia
– From classic chemotherapy
• Hand-foot skin reaction
– Targeted therapies
– Callous and inflammation over sites of pressure and friction
• Immune mediated disorders affecting the hands and feet

48. • Tops of hands and feet
• From paclitaxel or
docetaxel
• Starts within days to
weeks
• Associated with nail pain
and lifting
Housholder AL and Adams BB. J Am Acad Dermatol. 2012; 67(3):e116-117.
Dorsal Hand-Foot Syndrome
Figures: LeBoeuf

49. Taxanes: Dorsal Hand-Foot Syndrome
Figures: LeBoeuf

50. Toxicity Prevention With
Frozen Gloves
Toxicity
Grade
Control Hands (N=45) Frozen Glove-Protected
Hands (n=45)
P
% 95% CI % 95% CI
Nail Toxicity
0 49 34-64 89 76-96 0.0001
1 29 16-44 11 4-24
2 22 11-37 0
Skin Toxicity
0 38 26-58 67 57-86 0.0001
1 44 33-65 22 12-40
2 9 3-23 2 0.1-13
Incomplete
Data
9 3-21 9 3-21
CI, confident interval
Scotte F, et al. J Clin Oncol. 2005;23(19):4424-9.

51. Frozen Gloves and Socks
“Elasto-gel Chemotherapy Hypothermia Slippers and Mitts”
Source figures: amazon.com

52. Matsumoto K, et al. Cancer Res 2009;69(24 Suppl):Abstract nr 1114.
http://iamnotcancer.blogspot.com/2012/07/on-finishing-chemotherapy.html

53. Taxanes:
Dorsal Hand-Foot Syndrome
Figures: LeBoeuf
Before and after cooling with ice packs wrapped
on feet but not toes

54. Hand Foot Syndrome
• Acral erythema/palmoplantar erythrodysesthesia (PPE)
• Seen most commonly with capecitabine, cytarabine
doxorubicin/liposomal doxorubicin and 5-Fluorouracil
• Onset weeks to months
• Palms and soles
• Tingling and burning pain
• Sharply demarcated redness and swelling
– May develop into blistering, ulcers or wounds
5-FU, fluorouracil

55. Hand Foot Syndrome
Figure courtesy of Stephanie Liu, MD

56. Hand Foot Syndrome
Figures: LeBoeuf

57. Hand Foot Syndrome
Figures: LeBoeuf

58. Capecitabine HFS
HFS, hand-foot syndrome
Hoesly FJ, et al. Arch Dermatol. 2011;147(12):1418-23.
Complicated by infection, sepsis and death

59. Capecitabine HFS
After 19 Months
HFS, hand-foot syndrome
Figures: LeBoeuf

60. HFS: Management Strategies
• Grade 0: None
– Gentle skin care
– Capecitabine: Celecoxib 200mg twice a day
• Grade 1: Mild
– Topical high potency steroid twice a day
– Capecitabine: Celecoxib 200mg twice a day
• Grade 2: Moderate
– Topical high potency steroid twice a day
– Pain control
– Capecitabine: Celecoxib 200mg twice a day
• Grade ≥3: Severe
– All of the above
– Hold therapy until grade 1
– Then as above for grade 2
Rosen A, et al. (2013) Management Algorithms, in Dermatologic Principles and Practice in Oncology: (ed M. E. Lacouture),
John Wiley & Sons, Ltd, Oxford, UK

61. Hand-Foot Skin Reaction
• Starts between days 2 and 24 days (average 15)
with scaling, swelling, redness then dryness and
peeling
– Pain may be worse than the appearance
• Tender thickened lesions, with or without blisters,
surrounding rim of redness
• More pronounced on areas with increased
pressure and friction
• Most common with multikinase inhibitors
Lacouture ME, et al. Ann Oncol. 2008;19(11):1955-61
Lipworth AD, et al. Oncology 2009;77(5):257-71

62. Incidence of HFSR (%)
0
10
20
30
40
50
60
70
Axitinib Cabozatinib Pazopanib Regorafenib Sorafenib Sunitinib
All grade High grade
High-grade = Grade 3 (severe) according to the NCI-CTCAE (National Cancer Institute’s Common Terminology Criteria for Adverse
Events ) v3.0 or V4.03= ulcerative dermatitis or skin changes with pain interfering with function.
Belum VR, et al. Invest New Drugs. 2013;31:1078-1086. Belum VR, et al. Clin Exp Dermatol. 2016 Jan;41(1):8-15.

63. Hand Foot Skin Reaction
HFSR, hand-foot skin reaction
Lipworth AD, et al. Oncology 2009;77(5):257-71

64. SMALL STUDIES
• Clobetasol, cetirizine, cold sponging
• Topical steroids with keratolytics
• Narrow band UVB
• Topical PUVA
• Topical steroids, ‘podiatric care’ and
thermal water gel
• Pregabalin
• Topical prednicarbate ointment,
fusidic acid cream, dexpanthenol
• 10% Urea
• Hydrocolloid dressing containing
ceramide*
• Topical heparin, shock absorbers
and moisturizers
• Vitamin E 300mg/day
• Taohongsiwu (Chinese herbal)
What’s Been Studied?
CASES
UVB, Ultraviolet B; PUVA, psoralen-ultraviolet A
Summarized from McClellan B, et al. Ann Oncol. 2015;26(10):2017-26
Lots of approaches to HFSR
No homerun to date

65. HFSR: My/DFCI Approach
• Prior to starting therapy
– Skin exam and activity
assessment when possible
• Preferably with a dermatologist
– Treat pre-existing conditions
• Fungal disease (athlete’s foot)
• Dermatitis
• Calloused skin
– Pumice/friction, etc NOT
recommended after
starting therapy
HFSR, hand-foot skin reaction; DFCI, Dana-Farber Cancer Institute

66. What Can You Do to Minimize HFSR?
• Dry skin care
– Bland moisturizers
– Warm, not hot water
• 20% Urea cream twice
a day
• Avoid repetitive tasks
or vigorous exercise
• Lubricate hands and
feet in anticipation of
activity

67. What Can You Do to Minimize HFSR?
• Avoid repetitive tasks
or vigorous exercise
• Lubricate feet like a
marathoner
in anticipation of
activity
• Wear well fitting shoes
• Athletic socks
– Cotton is ok for
everyday use, but
athletic socks* better
handle moisture

68. Cotton Socks?
• “RULE #1 - Keep the cotton socks out of the
running shoes! Why? Cotton retains moisture
and when you have moisture, heat, and
friction in a running shoe you are more likely
to get blisters, calluses, and hot spots. Also,
cotton gets more abrasive when wet, again
not good in a running shoe.”
https://www.sockgeek.com/pages/running-socks-101.

69. What Can You Do to Minimize HFSR?
• Dry skin care
• 20% Urea cream twice a day
• Avoid repetitive tasks or
vigorous exercise
• Lubricate feet like a
marathoner in anticipation
of activity
• Wear well fitting shoes
• Wear athletic socks
• *Same story for scrotal
irritation

70. HFSR: My/DFCI Approach
• For severe cases, we add
therapies to treat the changes
that resemble psoriasis
• Oral retinoids can help pain and
skin thickening
• Topical retinoids are being
studied for prevention of HFSR
– https://clinicaltrials.gov/ct2/show/NC
T04071756?term=tazarotene&draw=
2&rank=1
HFSR, hand-foot skin reaction; DFCI, Dana-Farber Cancer Institute

71. Conclusions
• Side effects of the skin, hair and nails are
common in patients undergoing treatment for
colorectal cancer.
• These side effects can greatly impact patient
quality of life and are associated with response
• There is some evidence (and lots of practical
approaches based on science) that can help
minimize the impact of these toxicities
• A team approach, including a dermatologist when
possible, can help!

72. “Connor’s case stresses…to
all of us, how important the
continuation of research is
– to not only find ways to
cure cancer, but ways to
cure it humanely”.
Jennifer Shepherd Flanagan, Connor’s Mom
To learn more about Connor:
http://connorflanaganfoundation.com/

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