Your SlideShare is downloading. ×
Gp ak feb22-leo
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Introducing the official SlideShare app

Stunning, full-screen experience for iPhone and Android

Text the download link to your phone

Standard text messaging rates apply

Gp ak feb22-leo

280
views

Published on

Published in: Health & Medicine

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
280
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
2
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide
  • This slide must be visually presented to the audience AND verbalized by the speaker.Instructions for completing this slide:If you have no relationships to disclose, simply indicate ‘‘Not Applicable’’ under the heading ‘‘Relationships with Commercial Interests’’
  • This slide must be visually presented to the audience AND verbalized by the speaker.Instructions for completing this slide:Where a program has received no commercial support (this includes monies for food, logistics assistance such as registration, AV set-up, etc.), simply indicate ‘‘No Commercial Support’’
  • This slide must be visually presented to the audience AND verbalized by the speaker.Instructions for completing this slide:Where there are no potential biases identified in Slides 2 AND 3, simply indicate ‘‘Not Applicable’’
  • ReferencesCriscione VD, Weinstock MA, Naylor MF, et al; Department of Veteran Affairs Topical Tretinoin Chemoprevention Trial Group. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523-30.Lober BA, Lober CW. Actinic keratosis is squamous cell carcinoma. South Med J. 2000;93:650-5.Rogers HW, Weinstock, MA, Harris, AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146(3):283-7.Chen J, Ruczinski I, Jorgenson TJ. Nonmelanoma skin cancer and risk for subsequent malignancy. J Natl Cancer Inst. 2008;100:1215-22.
  • Those SCC lesions that do not arise from or near an AK lesion are de novo lesions.ReferencesCriscione VD, Weinstock MA, Naylor MF, et al; Department of Veteran Affairs Topical Tretinoin Chemoprevention Trial Group. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523-30.Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87(4):201-7.Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet. 1988;1(8589):795-7.Mittelbronn MA, Mullins DL, Ramos-Caro FA, et al. Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma. Int J Dermatol. 1998;37:677-81.Dinehart SM, Nelson-Adesokan P, Cockerell C, et al. Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis. Cancer. 1997;79:920-3.
  • ReferencesDiepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol.2002;146(suppl 61):1-6.Berman B, Bienstock L, Kuritzky L, et al. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006;55(5):suppl 1-8.Hemminki K, Zhang H, Czene K. Time trends and familial risks in squamous cell carcinoma of the skin. Arch Dermatol. 2003;139:885-9.Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87(4):201-7.Goldberg LH, Mamelak AJ. Review of actinic keratosis. Part I: etiology, epidemiology and clinical presentation. J Drugs Dermatol. 2010;9(9):1125-32.
  • ReferencesUlrich M, Krueger-Corcoran D, Roewert-Huber J, et al. Reflectance confocal microscopy for non-invasive monitoring of therapy and detection of subclinical actinic keratoses. Dermatology. 2010;220(1):15-24.Berman B, Amini S, Valins W, et al. Pharmacotherapy of actinic keratosis. Expert Opin Pharmacother. 2009;10(18):3015-31.Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000;42(1 Pt 2):4-7.Berman B, Bienstock L, Kuritzky L, et al. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006;55(5):suppl 1-8.
  • AK is often described as a field disease and not limited to single clinically visible lesions. Patients presenting with multiple visible AKs may also have non-visible changes to a larger area of the sun exposed skin. These lesions will appear subsequently at a later time, which is why high recurrence rates are often seen. The understanding of AK pathophysiology, particularly in terms of its close relationship and parallels to SCC in situ, has grown substantially, further heightening the importance of treating AKs at all levels of its severity/progression.1In the past few years, the therapeutic algorithm for AK has changed and topical applied treatments are now preferred compared to lesion-directed therapy. The concept of field cancerisation and the classification of AK as an early SCC in situ have contributed to these developments.2Considering that AK lesions represent a step in the continuous process from keratinocyte atypia to invasive SCC, we currently aim to clear the whole actinically damaged field. Furthermore, topical management with clearance of all AK and also clinically not visible so-called “subclinical” lesions may significantly reduce recurrence rates.2ReferencesMartin G. The impact of the current United States guidelines on the management of actinic keratosis: is it time for an update? J Clin Aesthet Dermatol. 2010;3(11):20-5.Ulrich M, Drecoll U, Stockfleth E. Emerging drugs for actinic keratosis. Exp Opin Emerg Drugs. 2010;15(4):545-55.
  • Product monograph indications related to AK:5-FU: Topical treatment of premalignant keratosesImiquimod 3.75%: The topical field (area) treatment of multiple clinically typical, visible or palpable actinic keratoses (AK), whether presenting at the start of therapy or revealed during therapy, of the face or balding scalp in adults.Imiquimod 5%: Treatment of clinically typical, non-hyperkeratotic, non-hypertrophic actinic keratosis on the face or balding scalp.Ingenol mebutate 0.015%: Topical treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis (AK) on the face and scalp in adults.Ingenol mebutate 0.05%: Topical treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis (AK) on the trunk and extremities in adults.Aminolevulinic acid with PDT: Treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp.Methyl aminolevulinate with PDT: Treatment of thin or non-hyperkeratotic and non-pigmented actinic keratosis on the face and scalp when other therapies are considered less appropriate.ReferencesValeant Canada Ltd. Product monograph. EFUDEX® (fluorouracil) Topical Cream. December 15, 2004.Medicis Canada Ltd. Product monograph. ZYCLARA® (imiquimod) Cream, 3.75%. May 17, 2012.Medicis Canada Ltd. Product monograph. ALDARA® (imiquimod) Cream, 5%. February 20, 2012.LEO Pharma Inc. Product monograph. PICATO® (ingenol mebutate) Topical Gel, 0.015% and 0.05%. January 30, 2013.DUSA Pharmaceuticals, Inc. Product monograph. Levulan Kerastick® (aminolevulinic acid hydrochloride). March 30, 2004.Galderma Canada Inc. Product monograph. METVIX™ (methyl aminolevulinate). February 26, 2009.
  • ReferencesJorizzo J, Steward D, Bucko A, et al. Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis. Cutis. 2002;70(6):335-9.Weiss J, Menter A, Hevia O, et al. Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. Cutis. 2002;70(2 Suppl):22-9.Tanghetti E, Werschler P. Comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp. J Drugs Dermatol. 2007;6(2):144-7.Krawtchenko N, Roewert-Huber J, Ulrich M, et al. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007;157(Suppl 2):34-40.Medicis Canada Ltd. Product monograph. ZYCLARA® (imiquimod) Cream, 3.75%. May 17, 2012.Hanke CW, Swanson N, Bruce S, et al. Complete clearance is sustained for at least 12 months after treatment of actinic keratoses of the face or balding scalp via daily dosing with imiquimod 3.75% or 2.5% cream. J Drugs Dermatol. 2011 Feb;10(2):165-70.Medicis Canada Ltd. Product monograph. ALDARA® (imiquimod) Cream, 5%. February 20, 2012.Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012;366(11):1010-9.Tschen EH, Wong DS, Pariser DM, et al. Photodynamic therapy using aminolevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: phase IV multicentre clinical trial with 12-month follow up. Br J Dermatol. 2006;155(6):1262-9.Piacquadio DJ, Chen DM, Farber HF, et al. Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials. Arch Dermatol. 2004;140(1):41-6.Pariser DM, Lowe NJ, Stewart DM, et al. Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial.J Am Acad Dermatol. 2003;48(2):227-32.
  • Referencede Berker D, McGregor JM, Hughes BR. Guidelines for the management of actinic keratoses. Br J Dermatol. 2007;156:222-30.
  • Use of field-base therapy improves outcomes in reducing number of AK lesions whether used before or after cryosurgery. In a study by Jorizzo et al. in 2010, field-based therapy (imiquimod in this study) improved clearance of cryotherapy-treated lesions in addition to clearing AKs on its own.References1. Jorizzo J, Weiss J, Furst K, et al. Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial.Arch Dermatol. 2004;140(7):813-6.2. Jorizzo J, Markowitz O, Lebwohl MG, et al. A randomized, double-blinded, placebo-controlled, multicenter, efficacy and safety study of 3.75% imiquimod cream following cryosurgery for the treatment of actinic keratoses. J Drugs Dermatol. 2010;9:1101-8.
  • Note that ingenol mebutate 0.05% is the only topical therapy indicated for the treatment of AK lesions on the extremities or trunk.
  • ReferenceBerman B, Bienstock L, Kuritzky L, et al. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract. 2006;55(5):suppl 1-8.
  • In recent years, the therapeutic algorithm for AK has changed such that topical treatments are preferred compared to lesion-directed therapy. The concept of field cancerisation and the classification of AK as an early SCC in situ have contributed to these developments.3Considering that AK lesions represent a step in the continuous process from keratinocyte atypia to invasive SCC, the aim should be to clear the whole actinically damaged field. Topical management with clearance of all visible lesions and non-visible lesions may significantly reduce recurrence rates.3Referencesde Berker D, McGregor JM, Hughes BR. Guidelines for the management of actinic keratoses. Br J Dermatol. 2007;156:222-30.Martin G. The impact of the current United States guidelines on the management of actinic keratosis: is it time for an update? J Clin Aesthet Dermatol. 2010;3(11):20-25.Ulrich M, Drecoll U, Stockfleth E. Emerging drugs for actinic keratosis. Exp Opin Emerg Drugs. 2010;15(4):545-555.LEO Pharma. Market research data on file. 2011.
  • ReferencesValeant Canada Ltd. Product monograph. EFUDEX® (fluorouracil) Topical Cream. December 15, 2004.Medicis Canada Ltd. Product monograph. ZYCLARA® (imiquimod) Cream, 3.75%. May 17, 2012.Medicis Canada Ltd. Product monograph. ALDARA® (imiquimod) Cream, 5%. February 20, 2012.LEO Pharma Inc. Product monograph. PICATO® (ingenol mebutate) Topical Gel, 0.015% and 0.05%. January 30, 2013.DUSA Pharmaceuticals, Inc. Product monograph. Levulan Kerastick® (aminolevulinic acid hydrochloride). March 30, 2004.Galderma Canada Inc. Product monograph. METVIX™ (methyl aminolevulinate). February 26, 2009.
  • Note to speaker: While some of these adverse events may be described as local or application site reactions, the term "Local Skin Reaction" refers to an FDA-approved definition that comprises only 6 attributes: erythema, flaking/scaling, crusting, vesiculation/pustulation, swelling, and erosion. This definition was developed to assess expected skin reactions with AK topical treatment numerically in trials. While other events like pain, pruritus, and irritation are local, and are skin reactions, they can not be called "local skin reactions" as per the FDA definition in relation to AK.ReferencesValeant Canada Ltd. Product monograph. EFUDEX® (fluorouracil) Topical Cream. December 15, 2004.Cheigh NH. Dermatologic drug reactions and self-treatable skin disorders. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw-Hill Inc;2008:1584-5.Medicis Canada Ltd. Product monograph. ZYCLARA® (imiquimod) Cream, 3.75%. May 17, 2012.Medicis Canada Ltd. Product monograph. ALDARA® (imiquimod) Cream, 5%. February 20, 2012.LEO Pharma Inc. Product monograph. PICATO® (ingenol mebutate) Topical Gel, 0.015% and 0.05%. January 30, 2013.DUSA Pharmaceuticals, Inc. Product monograph. Levulan Kerastick® (aminolevulinic acid hydrochloride). March 30, 2004.Galderma Canada Inc. Product monograph. METVIX™ (methyl aminolevulinate). February 26, 2009.
  • ReferencesValeant Canada Ltd. Product monograph. EFUDEX® (fluorouracil) Topical Cream. December 15, 2004.Medicis Canada Ltd. Product monograph. ZYCLARA® (imiquimod) Cream, 3.75%. May 17, 2012.Medicis Canada Ltd. Product monograph. ALDARA® (imiquimod) Cream, 5%. February 20, 2012.LEO Pharma Inc. Product monograph. PICATO® (ingenol mebutate) Topical Gel, 0.015% and 0.05%. January 30, 2013.
  • ReferencesValeant Canada Ltd. Product monograph. EFUDEX® (fluorouracil) Topical Cream. December 15, 2004.Cheigh NH. Dermatologic drug reactions and self-treatable skin disorders. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw-Hill Inc;2008:1584-5.
  • ReferencesMedicis Canada Ltd. Product monograph. ZYCLARA® (imiquimod) Cream, 3.75%. May 17, 2012.Medicis Canada Ltd. Product monograph. ALDARA® (imiquimod) Cream, 5%. February 20, 2012.
  • ReferenceLEO Pharma Inc. Product monograph. PICATO® (ingenol mebutate) Topical Gel, 0.015% and 0.05%. January 30, 2013.
  • Transcript

    • 1. Actinic Keratosis: New Solutions for the Primary Care Physician Actinic Keratosis: New Solutions for The Primary Care Physician Marcie Ulmer MD FRCPC FAAD Clinical Instructor Department of Dermatology & Skin Science University of British Columbia
    • 2. Actinic Keratosis: New Solutions for the Primary Care Physician Faculty/Presenter Disclosure • Faculty: Marcie Ulmer MD FRCPC FAAD • Relationships with commercial interests: – Speakers Bureau/Honoraria: Valeant Canada, Leo Pharma, Inc. – Consulting Fees: Valeant Canada, Leo Pharma, Inc.
    • 3. Actinic Keratosis: New Solutions for the Primary Care Physician Disclosure of Commercial Support • This program has received financial support from Leo Pharma, Inc. in the form of an educational grant • This program has received in-kind support from Leo Pharma, Inc. in the form of logistical support • Potential for conflict(s) of interest: – Dr. Marcie Ulmer has received funding from Leo Pharma, Inc. and Valeant Canada whose products are being discussed in this program. – Leo Pharma, Inc. and Valeant Canada benefit from the sale of products that will be discussed in this program: ingenol mebutate, 5-fluorouracil and Imiquimod.
    • 4. Actinic Keratosis: New Solutions for the Primary Care Physician Mitigating Potential Bias • Information will be presented supporting multiple therapeutic options for the treatment of actinic keratoses
    • 5. Case 1: Denise Diagnosis and Treatment of Actinic Keratosis Lesions
    • 6. Learning Objectives After attending this session, participants will be able to: • Explain the link between actinic keratosis (AK) and non-melanoma skin cancers (NMSC) • Identify the clinical signs and symptoms of actinic keratosis lesions • Describe current treatment options for actinic keratosis
    • 7. Patient Profile • Female, age 63 years • Non-smoker • Spends time outdoors gardening, swimming, and golfing in the summer, cross-country skiing in the winter • History of sunburn as both a child and adult • Conscientious about using sunscreen and wearing a hat for past 10+ years
    • 8. Prior Medical History • History of AK lesions 12 months ago (2 on back of right hand, 2 on right forearm) – Treated successfully with cryosurgery by family physician • History of basal cell carcinoma over past 15 years (3 on chest, 2 on back) – Excised/biopsied by dermatologist
    • 9. Discussion Question 1. True or false: There is a link between actinic keratosis and non-melanoma skin cancer. A. True B. False
    • 10. Actinic Keratoses and Non-melanoma Skin Cancer • AK is pre-cancerous skin lesion1,2 • Non-melanoma skin cancer (NMSC) includes squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) – NMSC is the most common type of cancer3 – A history of NMSC increases the risk for malignant melanoma and other types of cancer, including colon, lung, and breast cancer4 1. Criscione VD, et al. Cancer. 2009;115(11):2523-30. 2. Lober BA, et al. South Med J. 2000;93:650-5. 3. Rogers HW, et al. Arch Dermatol. 2010;146(3):283-7. 4. Chen J, et al. J Natl Cancer Inst. 2008;100:1215-22.
    • 11. Actinic Keratoses and NMSC SCC • AK lesions may progress to SCC1-3 – Progress less often to BCC4 • AK lesions and SCC are frequently contiguous as they share the same genetic alterations and morphology5,6 1. Marks R, et al. Lancet. 1988;1:795-7. 2. Mittelbronn MA, et al. Int J Dermatol. 1998;37:677-81. 3. Dinehart SM, et al. Cancer. 1997;79:920-3. 4. Criscione VD, et al. Cancer. 2009;115(11):2523-30. 5. Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8. 6. Feldman SR, et al. Cutis. 2011; 87:201-7. © Diepgen TL, Yihune G, et al. Dermatology Online Atlas. AK
    • 12. Natural History of AK Lesions • Natural course of AK lesions is unpredictable1-5 – Estimates of 40 to 80% of cutaneous SCCs arise from, or near, an AK lesion2-5 • AK lesions may persist, regress, or progress1,3 – Some lesions that regress will recur, from 32% within 1 year to 92% within 5 years – Progression identified as hypertrophic AK, SCC in situ (Bowen’s disease), and/or invasive SCC 1. Criscione VD, et al. Cancer. 2009;115(11):2523-30. 2. Feldman SR, et al. Cutis. 2011;87(4):201-7. 3. Marks R, et al. Lancet. 1988;1(8589): 795-7. 4. Mittelbronn MA, et al. Int J Dermatol. 1998;37:677-81. 5. Dinehart SM, et al. Cancer. 1997;79:920-3.
    • 13. Discussion Question 2. Which of the following is not a risk factor for development of actinic keratosis lesions? A. B. C. D. E. F. G. Male gender Light-coloured eyes and hair Cumulative exposure to UV radiation Excessive/habitual alcohol consumption Fair skin Immunosuppression All of the above are risk factors
    • 14. General Risk Factors for AK • • • • High intensity or cumulative exposure to UV radiation1,2 Use of tanning beds or sunlamps3 Prior history of AKs or other skin cancer4 Clinical signs of photodamage, such as solar/senile lentigines, facial telangiectasia, and actinic elastosis of the neck4 • Immunosuppression5 • Human papillomaviruses may play a role in etiology of AKs5 1. Diepgen TL, et al. Br J Dermatol.2002;146(suppl 61):1-6. 2. Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8. 3. Hemminki K, et al. Arch Dermatol. 2003;139:885-9. 4. Feldman SR, et al. Cutis. 2011;87(4):201-7. 5. Goldberg LH, et al. J Drugs Dermatol. 2010;9(9):1125-32.
    • 15. Red or blond hair Male gender Light-coloured eyes Fair skin Older age, especially those age 50 years and older … But also seen in individuals aged 20 to 50 years Individual Susceptibility Factors for AK Salasche SJ. J Am Acad Dermatol. 2000;42(1 Pt 2):4-7.
    • 16. Individual Susceptibility Factors for AK 1 1 2-4 Classification Response to UV rays Skin colour I Never tans, always burns White II Tans with difficulty, usually burns White III Average tanning, sometimes burns White IV Easily tans, rarely burns Moderate Brown V Very easy to tan, very rarely burns Hispanic, Latin, African, Asian, Indian VI Never burns Black 1. Fitzpatrick TB. J Med Esthet. 1975;2:33034. 2. Sng J, et al. J Am Acad Dermatol. 2009;61(3):426-32. 3. Ahluwalia J, et al. J Drugs Dermatol. 2012;11(4):484-6. 4. Davis SA, et al. J Drugs Dermatol. 2012;11(4):466-73.
    • 17. Denise’s Recent History • 2 months ago, Denise returned to her physician because she found a “suspicious spot” on her forehead • The lesion had the appearance of an AK lesion • The physician also noted a small rough patch next to the more visible lesion that he concluded was also an AK lesion
    • 18. Discussion Question 3. Which of the following is not a clinical sign or symptom of actinic keratosis lesions? A. Lesions are usually less than 1 cm in diameter B. Lesions are generally found on sun-exposed areas of the body C. Visible lesions are usually brown to dark brown D. Lesions may be rough and/or scaly to the touch
    • 19. Clinical Signs of Actinic Keratosis Lesions • Visible/detectable lesions are reddish to reddish brown, rough, scaly patches less than 1 cm in diameter1 • Non-visible, non-palpable lesions occur up to 10 times more often than visible lesions, particularly in sundamaged skin2 – >80% of all AK lesions are found on sun-exposed areas of the body3 1. Ulrich M, et al. Dermatology. 2010;220(1):15-24. 2. Berman B, et al. Expert Opin Pharmacother. 2009;10(18):3015-31. 3. Salasche SJ. J Am Acad Dermatol. 2000;42(1 Pt 2):4-7. 4. Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8. Courtesy of Dr. Kirk Barber . When one AK is seen, assume that other, perhaps non-visible, AK lesions exist4
    • 20. Clinical Signs of Actinic Keratosis Lesions • Lesions can often be felt more easily than seen1 • Red, rough, scaling spots2 • White scale over a pink macule or papule1 • Pinhead to 4–5 mm in diameter1 • Distribution: solitary, clustered, or disseminated1 • Generally asymptomatic1,2 © DermNet NZ; dermnetnz.org. 1. Stulberg D, et al. Am Fam Physician. 2004;70(8):1481-8. 2. Canadian Dermatology Association. Actinic keratoses fact sheet. 2012.
    • 21. Examples of AK Lesions Photos: © DermNet NZ; dermnetnz.org.
    • 22. Differential Diagnosis of AK Lesions Bowen’s disease (SCC in situ) Keratoacanthoma BCC Invasive SCC Duncan KO, et al. In: Wolff K, et al. Fitzpatrick's Dermatology in General Medicine: 7th ed. 2008:Chapter 113. Photos, top and bottom left, top and bottom right, © Danderm; www.danderm-pdv.is.kkh.dk. Photo, centre, © DermNet NZ; dermnetnz.org. Lentigo maligna
    • 23. The Differential Diagnosis of AK Lesions Verruca vulgaris Solar lentigo Seborrheic keratosis Lichen planus Discoid lupus erythematosus Duncan KO, et al. In: Wolff K, et al. Fitzpatrick's Dermatology in General Medicine: 7th ed. 2008:Chapter 113. Photos: Top left, bottom right, © Danderm; www.danderm-pdv.is.kkh.dk. Top centre and right, © DermNet NZ; http://dermnetnz.org. Bottom left, © DermAtlas; www.DermAtlas.org.
    • 24. Discussion Question 4. Which of the following factors should be considered when selecting treatment for actinic keratosis lesions? A. Number of lesions B. Location of lesions C. Potential for presence of subclinical (non-visible, non-palpable) lesions D. All of the above E. A and B only
    • 25. Actinic Keratosis Is a Field Disease • Field of cancerisation surrounds clinical AK lesions and is partially or completely clinically invisible – multifocal, paraneoplastic, subclinical changes1 • Histopathology of AKs is found in surrounding skin2 • Clinical lesions Subclinical (non-palpable, nonvisible) AK lesions occur ~10 times more often than clinical AK lesions in sun-damaged skin3 Subclinical lesions 1. Vatve M, et al. Br J Dermatol. 2007;157(Suppl 2):21-4. 2. Berman B, et al. Exp Opin Pharmacother. 2009;10(18):3015-31. 3. Braakhuis BJM, et al. Cancer Res. 2003;63(8):1727-30.
    • 26. Is Field Treatment the Necessary Approach? • It is impossible to know which AK lesions will progress to invasive SCC, so it is recommended that all AK lesions be treated1 • The ultimate goal of treatment is to clear the entire actinically damaged field2 – Addressing both clinical and non-visible lesions may significantly reduce recurrence rates of AK2 • Early diagnosis and treatment of the field of actinic damage decreases overall disease burden and helps to prevent development of invasive SCC1,2 1. Martin G. J Clin Aesthet Dermatol. 2010;3(11):20-5. 2. Ulrich M, et al. Exp Opin Emerg Drugs. 2010;15(4):545-55.
    • 27. Discussion Question 5. Which of the following topical medications is not indicated for field-directed treatment of AK lesions? A. B. C. D. E. Imiquimod 3.75% Tretinoin cream 0.025% Ingenol mebutate 0.015% 5-fluorouracil B and C
    • 28. Field-directed Topical Treatment Options Treatment Dosing Duration of treatment 5-fluorouracil (5-FU)1 Twice daily Usual duration: 2-4 weeks Imiquimod 3.75% (face, balding scalp)2 Up to 2 packets once daily 6 weeks (2 treatment cycles of 2 weeks, separated by a 2-week no-treatment period) Imiquimod 5% (face, balding scalp)3 Twice weekly 16 weeks Ingenol mebutate 0.015% (face, scalp)4 Once daily 3 consecutive days Ingenol mebutate 0.05% (trunk, extremities)4 Once daily 2 consecutive days Aminolevulinic acid5 or methyl aminolevulinate6 with PDT Agents applied a day5 or a few hours6 before light treatment 15 to 26 treatment cycles May be retreated 8+ weeks5 or 3+ months6 after initial treatment 1. EFUDEX® product monograph, 2004. 2. ZYCLARA® product monograph, 2012. 3. ALDARA® product monograph, 2012. 4. PICATO® product monograph, 2013. 5. Levulan Kerastick® product monograph, 2004. 6. METVIX™ product monograph, 2009.
    • 29. Efficacy of Field-directed Topical Therapies Treatment Complete clearance, % patients Follow-up period Patients with sustained clearance, % Follow-up period 5-FU 48–58%1-3 4 weeks 54%4 12 months Imiquimod 3.75%* 36%5 8 weeks 41%6 12 months Imiquimod 5%7* 45% 8 weeks 43% 12-18 months Ingenol mebutate 0.015%*8 42% 57 days 46% 12 months Ingenol mebutate 0.05%8 34% 57 days 50% 12 months 47–82%9-11 1–3 months 40%9 12 months Photodynamic therapy (PDT) Between-study comparisons are not intended due to differences in patient demographics and other study parameters. *Indicated for face and scalp only. 1. Jorizzo J, et al. Cutis. 2002;70(6):335-9. 2. Weiss J, et al. Cutis. 2002;70(2 Suppl):22-9. 3. Tanghetti E, et al. J Drugs Dermatol. 2007;6(2):144-7. 4. Krawtchenko N, et al. Br J Dermatol. 2007;157(Suppl 2):34-40. 5. ZYCLARA® product monograph, 2012. 6. Hanke CW, et al. J Drugs Dermatol. 2011;10(2):165-70. 7. ALDARA® product monograph, 2012. 8. Lebwohl M, et al. New Engl J Med. 2012;366(11):1010-9. 9. Tschen EH, et al. Br J Dermatol. 2006;155(6):1262-9. 10. Piacquadio DJ, et al. Arch Dermatol. 2004;140(1):41-6. 11. Pariser DM, et al. J Am Acad Dermatol. 2003;48(2):227-32.
    • 30. Lesion-directed Treatment Options • Physically destructive methods – Cryosurgery – Laser ablation • Surgical removal – Shave excision – Curettage – Electrodessication de Berker D, et al. Br J Dermatol. 2007;156:222-30.
    • 31. Combination/Sequential Therapy • Cryosurgery to treat visible AK lesions + topical treatment to treat underlying field cancerisation: – 5-FU followed by cryosurgery1 – Cryosurgery followed by 3.75% imiquimod2 1. Jorizzo J, et al. Arch Dermatol. 2004;140:813-6. 2. Jorizzo J, et al. J Drugs Dermatol. 2010;9:1101-8.
    • 32. Denise’s Recent Treatment • Because of concerns about field cancerisation and Denise’s desire for a non-surgical treatment on her forehead, her physician prescribed ingenol mebutate 0.015%, once daily for 3 days
    • 33. Treatment Follow-up • Two months later, Denise returns for a follow-up appointment to check on clearance of forehead lesions • At this appointment, she points out another “suspicious spot” located near the scar from removal of an earlier AK lesion on her right hand – Her physician diagnoses it as an AK lesion
    • 34. Discussion Question 6. What treatment would you recommend for this new AK lesion on Denise’s hand? A. B. C. D. E. Cryosurgery ± 5-FU 5-FU monotherapy Imiquimod 5% Ingenol mebutate 0.05% Other
    • 35. Summary • Actinic keratoses are pre-cancerous skin lesions that may progress to SCC; progression is unpredictable • Risk factors for development of AK lesions include: – – – – – Amount of cumulative/prolonged exposure to UV Fair skin Light-coloured hair/eyes Older age Male gender • AK lesions may be visible or non-visible/non-palpable • Effective treatment of AK lesions may help to prevent recurrence and/or progression to SCC
    • 36. Case 2: Frank Treating Actinic Keratosis Lesions and Counselling Patients
    • 37. Learning Objectives After attending this session, participants will be able to: • Describe the expected local skin reactions for various topical, field-directed treatment options for actinic keratosis (AK) • Identify other potential adverse effects of topical AK therapies • Discuss key messages when counselling patients about the application of topical AK therapies and potential local skin reactions
    • 38. Patient Profile • Male, age 58 years • Non-smoker (quit 15 years ago) • Sedentary lifestyle; doesn’t participate in outdoor activities or sports • History of sunburn as both a child and adult • Freckled skin on torso, arms, legs, face, and scalp • “Never” remembers to wear sunscreen unless his wife reminds him
    • 39. Frank’s Recent History • During a routine physical, Frank’s family physician noticed reddish lesions on Frank’s scalp, some of which had white scaling • Upon further examination, the physician noted 2 lesions that were palpable (rough to the touch, like grains of salt) but not readily visible, for a total of 7 lesions
    • 40. Prior Medical History • No prior history of non-melanoma skin cancer (squamous cell carcinoma and basal cell carcinoma) or AK lesions • Family history of melanoma (father, age 72 years)
    • 41. Frank’s Risk Factors for AK Lesions • Sun-damaged skin as evidenced by number and distribution of lentigines • Tans with difficulty, usually burns • History of sunburn • Male gender • Age (over 50 years) • Fair skin • Light-coloured eyes
    • 42. Discussion Question 7. What is the recommended strategy for treatment of multiple AK lesions? A. Lesion-directed therapy (cryosurgery, shave excision, curettage, etc.) B. Field-directed topical therapy C. Sequential/combination therapy (e.g., topical 5-FU followed by cryosurgery) D. Any of the above E. B or C only
    • 43. AK Treatment Strategies • Primary treatment decision point: is it a single AK lesion vs. multiple lesions? • Single lesion: – Consider lesion-directed therapy – If there is evidence of extensive photodamage, consider field-directed therapy to treat potential subclinical AK lesions • Multiple lesions: – Consider sequential/combination therapy – If there are a significant number of AK lesions in an area, consider field-directed therapy Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8.
    • 44. Other Factors to Consider When Selecting Treatment • • • • • Size of lesions1 Typical vs. atypical lesions1 Well defined vs. poorly defined lesions1 Location of lesions1 The potential for field cancerisation (non-visible lesions)2,3 • Patient’s desire to improve appearance of photoaged skin4 1. de Berker D, et al. Br J Dermatol. 2007;156:222-30. 2. Martin G. Clin Aesthet Dermatol. 2010;3(11):20-5. 3. Ulrich M, et al. Exp Opin Emerg Drugs. 2010;15(4):545-55. 4. LEO Pharma. Market research data on file. 2011.
    • 45. Discussion Question 8. What treatment would you recommend for the 7 AK lesions on Frank’s scalp? A. B. C. D. E. F. 5-FU monotherapy Imiquimod 3.75% Imiquimod 5% Ingenol mebutate 0.015% Ingenol mebutate 0.05% Other
    • 46. Field-directed Treatments: Local Skin Reactions Treatment Local skin reactions 5-FU1 • Erythema, erosion, crusting, ulceration • Significant erythema, burning, erosion, crusting, and/or ulceration can occur during treatment and may require treatment interruption Imiquimod 3.75%, 5%2,3* • Erythema, flaking/scaling/dryness, scabbing/crusting • Intense local skin reactions including erythema, scabbing/crusting, and erosion/ulceration can occur after a few applications, and may require treatment interruption Ingenol mebutate 0.015%*, 0.05%4 • Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation • Typically occur within 1 day of treatment initiation and peak in intensity up to 1 week following completion of treatment • Usually resolve within 2 weeks on face and scalp and within 4 weeks on trunk and extremities Aminolevulinic acid or methyl aminolevulinate with PDT5,6 Erythema, edema, crusting Between-study comparisons are not intended due to differences in patient demographics and other study parameters. *Indicated for face and scalp only. 1. EFUDEX® product monograph, 2004. 2. ZYCLARA® product monograph, 2012. 3. ALDARA® product monograph, 2012. 4. PICATO® product monograph, 2013. 5. Levulan Kerastick® product monograph, 2004. 6. METVIX™ product monograph, 2009.
    • 47. Additional Question • How will you explain the time course of LSRs (topical agents) with your patients?
    • 48. Examples of LSRs This LSR comprises erythema, vesiculation, and mild swelling. This LSR comprises more pronounced swelling and erythema.
    • 49. Field-directed Treatments: Other Adverse Events Treatment Other adverse events 5-FU1,2 Application site pain, pruritus, burning, dermatitis, soreness, tenderness, hyperpigmentation, scarring Insomnia, stomatitis, suppuration, scaling, swelling, irritability, medicinal taste, photosensitivity, and lacrimation Laboratory abnormalities (leukocytosis, thrombocytopenia, toxic granulation, eosinophilia) Imiquimod 3.75%, 5%3,4* Target site pain, tenderness, bleeding, itching, stinging, burning, tingling, irritation, photosensitivity Flu-like symptoms, including malaise, fever, nausea, myalgias, and chills Exacerbation of inflammatory skin conditions Ingenol mebutate 0.015%*, 0.05%5 Administration site pruritus, irritation, pain, infection Periorbital pain Headache Eyelid edema Aminolevulinic acid or methyl aminolevulinate with PDT6,7 Stinging and burning during light therapy Application site itching, photosensitivity Between-study comparisons are not intended due to differences in patient demographics and other study parameters. *Indicated for face and scalp only. 1. EFUDEX® product monograph, 2004. 2. Cheigh NH. In: DiPiro JT, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 2008:1584-5. 3. ZYCLARA® product monograph, 2012. 4. ALDARA® product monograph, 2012. 5. PICATO® product monograph, 2013. 6. Levulan Kerastick® product monograph, 2004. 7. METVIX™ product monograph, 2009.
    • 50. Frank’s Treatment • Frank asked his physician if he could just “zap” off the lesions to get rid of them quickly • Because of the number of AK lesions (7) and the potential for non-visible lesions, Frank’s physician prescribed 5-FU twice daily for 21 days
    • 51. Setting Treatment Expectations • It is important that your patients… – – – – Understand the importance of field therapy Know all treatment options available Know the direct effects of treatment options Know that local skin reactions are a normal and expected part of topical therapy – Understand the side effects associated with every option and how to manage them – Recognize that new/additional AKs can recur after initial treatment
    • 52. Counselling Tips for Topical AK Therapies • Wash hands before and after applying treatment • Use care if applying the medication near the eyes, nostrils, or mouth • Some local skin reactions may become visible and/or cause discomfort EFUDEX® product monograph, 2004. ZYCLARA® product monograph, 2012. ALDARA® product monograph, 2012. PICATO® product monograph, 2013.
    • 53. Patient Counselling Tips: 5-FU • Before applying, wash the area to be treated with soap and water and dry carefully1 • Apply a thin layer of medication only to the affected area1 • Apply with cotton-tipped applicator or suitable glove1 • Do not cover treated area with a bandage or other dressing 1 • If the area being treated becomes painful with continued use, stop treatment for 1–3 days1 – An over-the-counter steroid may help to alleviate swelling and soreness2 • During treatment and for 1 to 2 months after treatment has ended, stay out of direct sunlight1 1. EFUDEX® product monograph, 2004. 2. Cheigh NH. In: DiPiro JT, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 2008:1584-5.
    • 54. Patient Counselling Tips: Imiquimod • Apply a thin layer of medication only to the affected area • Avoid washing or getting the area wet for 8 hours; after 8 hours, wash the area with mild soap and water • Stop treatment and contact the office if: – You have a severe local skin reaction; wash off the medication with mild soap and water – Skin breaks down – Sores develop during the first week of treatment – You have any skin reactions that affect your daily activities or do not go away – Your develop flu-like signs and symptoms, such as malaise, fever, nausea, muscle pain, and chills • Non-visible lesions may become visible during treatment • During treatment, avoid exposure to sunlight, a sunlamp, or a tanning bed ZYCLARA® product monograph, 2012. ALDARA® product monograph, 2012.
    • 55. Patient Counselling Tips: Ingenol Mebutate • • • • Apply gel gently with the fingertip to the treatment area Allow to dry for 15 minutes Avoid washing or touching the treated skin for 6 hours Avoid applying immediately after taking a shower or less than 2 hours before bedtime • Do not cover the treated area with a bandage or other type of dressing • If a local skin reaction does not improve, contact the office • Put medication in a refrigerator (2°C to 8°C) as soon as possible after picking it up from the pharmacy and always store it in the fridge PICATO® product monograph, 2013.
    • 56. Discussion Question 9. How often would you follow-up with Frank after cessation of treatment? A. B. C. D. 8 weeks initially, then twice a year 4-8 weeks initially, then twice a year 8 weeks initially, then once a year 2 weeks initially, then once a year
    • 57. Summary • When there is a significant number of AK lesions in one area, consider field-directed therapies to help ensure adequate treatment of both visible and non-visible lesions • Set treatment expectations with patients, including potential for adverse effects/local skin reactions • Follow-up/monitor patients for recurrence or malignant transformation