A randomized trial comparing simultaneous vs. sequential field treatment of actinic keratosis with ingenol mebutate on two separate areas of the head and body

G Pellacani, K Peris, C Guillen, F Clonier, T Larsson, R Venkata, S Puig, G Pellacani, K Peris, C Guillen, F Clonier, T Larsson, R Venkata, S Puig

Abstract

Background: Actinic keratoses (AKs) are precursors to invasive squamous cell carcinoma and can progress if untreated. Limited data support the use of ingenol mebutate to treat AKs on more than one area of the body simultaneously.

Objective: To investigate safety, efficacy and treatment satisfaction when treating separate areas simultaneously or sequentially with different concentrations of ingenol mebutate gel.

Methods: In this phase IIIb study (NCT01787383), patients with clinically visible, non-hyperkeratotic AKs on two separate treatment areas (face/scalp and trunk/extremities) were randomized to simultaneous or sequential treatment with ingenol mebutate gel (0.015% and 0.05%). Endpoints included composite local skin response (LSR) score 3 days after first application, complete AK clearance and percentage reduction in AKs at week 8.

Results: There were no statistically significant differences between simultaneous (n = 101) and sequential (n = 98) groups in composite LSR score (10.4 vs. 9.7), complete clearance (52.7% vs. 46.9%) or percentage reduction in AKs (83.4% vs. 79.1%). Mean composite LSR scores on face/scalp and trunk/extremities were similar for both groups. Adverse event (AE) incidence was comparable between groups, the most common treatment-related AEs being pruritus and pain at the application site.

Conclusion: Treating AKs with ingenol mebutate simultaneously or sequentially gave similar results in terms of tolerability (LSR score, AEs) and efficacy (complete clearance). Therefore, the physician and patient can select the most convenient treatment regimen, with confidence in achieving a similar outcome.

© 2015 LEO Pharma A/S. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons, Ltd. on behalf of European Academy of Dermatology and Venereology.

Figures

Figure 1
Figure 1
Study design and treatment schedule. AK, actinic keratosis; LSR, local skin response; SAE, serious adverse event; STA, selected treatment area; TSQM, Treatment Satisfaction Questionnaire for Medication.
Figure 2
Figure 2
Patient flow. AE, adverse event.
Figure 3
Figure 3
Composite LSR profiles for (a) face and scalp and (b) trunk and extremities. LSR, local skin response; SE, standard error.
Figure 4
Figure 4
Mean composite LSR score 3 days after treatment by anatomical location: LSR safety set. LSR, local skin response.
Figure 5
Figure 5
Complete clearance of AKs 8 weeks after treatment. AKs, actinic keratoses.

References

    1. Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH. A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 2003; 63: 1727–1730.
    1. Jonason AS, Kunala S, Price GJ et al Frequent clones of p53‐mutated keratinocytes in normal human skin. Proc Natl Acad Sci U S A 1996; 93: 14025–14029.
    1. Vanharanta S, Massague J. Field cancerization: something new under the sun. Cell 2012; 149: 1179–1181.
    1. Hu B, Castillo E, Harewood L et al Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling. Cell 2012; 149: 1207–1220.
    1. Lebwohl M. Actinic keratosis: epidemiology and progression to squamous cell carcinoma. Br J Dermatol 2003; 149(Suppl 66): 31–33.
    1. Rosen T, Lebwohl MG. Prevalence and awareness of actinic keratosis: barriers and opportunities. J Am Acad Dermatol 2013; 68: S2–S9.
    1. Criscione VD, Weinstock MA, Naylor MF, Luque C, Eide MJ, Bingham SF. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115: 2523–2530.
    1. Einspahr JG, Stratton SP, Bowden GT, Alberts DS. Chemoprevention of human skin cancer. Crit Rev Oncol Hematol 2002; 41: 269–285.
    1. Vatve M, Ortonne JP, Birch‐Machin MA, Gupta G. Management of field change in actinic keratosis. Br J Dermatol 2007; 157(Suppl 2): 21–24.
    1. Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol 2013; 169: 502–518.
    1. Berman B, Cockerell CJ. Pathobiology of actinic keratosis: ultraviolet‐dependent keratinocyte proliferation. J Am Acad Dermatol 2013; 68(Suppl 1): S10–S19.
    1. Stockfleth E, Ferrandiz C, Grob JJ, Leigh I, Pehamberger H, Kerl H. Development of a treatment algorithm for actinic keratoses: a European Consensus. Eur J Dermatol 2008; 18: 651–659.
    1. Berman B, Goldenberg G, Hanke CW et al Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12‐month results. J Drugs Dermatol 2014; 13: 741–747.
    1. Krawtchenko N, Roewert‐Huber J, Ulrich M, Mann I, Sterry W, Stockfleth E. 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.
    1. Rigel DS, Stein Gold LF. The importance of early diagnosis and treatment of actinic keratosis. J Am Acad Dermatol 2013; 68(Suppl 1): S20–S27.
    1. Flohil SC, van der Leest RJ, Dowlatshahi EA, Hofman A, De Vries E, Nijsten T. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol 2013; 133: 1971–1978.
    1. Green AC, Harwood CA, Lear J. Skin cancer prevention: recent evidence from randomized controlled trials. Curr Derm Rep 2012; 1: 123–130.
    1. Harvey I, Frankel S, Marks R, Shalom D, Nolan‐Farrell M. Non‐melanoma skin cancer and solar keratoses II analytical results of the South Wales Skin Cancer Study. Br J Cancer 1996; 74: 1308–1312.
    1. He W, Zhu F, Ma X et al Actinic skin damage and mortality ‐ the First National Health and Nutrition Examination Survey Epidemiologic Follow‐up Study. PLoS ONE 2011; 6: e19907.
    1. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988; 1: 795–797.
    1. Naldi L, Chatenoud L, Piccitto R, Colombo P, Placchesi EB, La Vecchia C. Prevalence of actinic keratoses and associated factors in a representative sample of the Italian adult population: results from the Prevalence of Actinic Keratoses Italian Study, 2003–2004. Arch Dermatol 2006; 142: 722–726.
    1. Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012; 366: 1010–1019.
    1. Lebwohl M, Shumack S, Gold LS, Melgaard A, Larsson T, Tyring SK. Long‐term follow‐up study of ingenol mebutate gel for the treatment of actinic keratoses. JAMA Dermatol 2013; 149: 666–670.
    1. Anderson L, Jarrett M, Schmieder G, Schumack S, Katsamas J, Welburn P. Tolerability and pharmacokinetics of ingenol mebutate 0.05% gel applied to treatment areas up to 100 cm2 on the forearm(s) of patients with actinic keratosis. J Clin Aesthet Dermatol 2014; 7: 19–29.
    1. Atkinson MJ, Sinha A, Hass SL et al Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes 2004; 2: 12.
    1. Rosen R, Marmur E, Anderson L, Welburn P, Katsamas J. A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy. Dermatol Ther 2014; 4: 207–219.
    1. Shergill B, Zokaie S, Carr AJ. Non‐adherence to topical treatments for actinic keratosis. Patient Prefer Adherence 2013; 8: 35–41.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner