Journal of the American Academy of Dermatology
Volume 60, Issue 6 , Pages 934-943 , June 2009

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis

  • Lawrence Anderson, MD, FACP

      Affiliations

    • Dermatology Associates of Tyler, Tyler, Texas
    • Corresponding Author InformationReprint requests: Lawrence Anderson, MD, FACP, 1367 Dominion Plaza, Tyler, TX 75703.
    • ,
  • George J. Schmieder, DO

      Affiliations

    • Park Avenue Dermatology, PA, Orange Park, Florida
    • ,
  • W. Philip Werschler, MD

      Affiliations

    • Premier Clinical Research, Spokane, Washington
    • ,
  • Eduardo H. Tschen, MD

      Affiliations

    • Academic Dermatology Associates, Albuquerque, New Mexico
    • ,
  • Mark R. Ling, MD, PhD

      Affiliations

    • MedaPhase, Inc., Newnan, Georgia
    • ,
  • Dow B. Stough, MD

      Affiliations

    • Burk Pharmaceutical Research, Hot Springs, Arkansas
    • ,
  • Janelle Katsamas

      Affiliations

    • Peplin Ltd, Brisbane, Australia

References 

  1. Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007;33:1099–1101
  2. Ackerman AB, Mones JM. Solar (actinic) keratosis is squamous cell carcinoma. Br J Dermatol. 2006;155:9–22
  3. Anwar J, Wrone DA, Kimyai-Asadi A, Alam M. The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classification schemes. Clin Dermatol. 2004;22:189–196
  4. Cockerell CJ. Histopathology of incipient intraepidermal squamous cell carcinoma (“actinic keratosis”). J Am Acad Dermatol. 2000;42:11–17
  5. Lober BA, Lober CW. Actinic keratosis is squamous cell carcinoma. South Med J. 2000;93:650–655
  6. Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000;42:23–24
  7. Dinehart SM, Nelson-Adesokan P, Cockerell C, Russell S, Brown R. Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis. Cancer. 1997;79:920–923
  8. Smith ES, Feldman SR, Fleischer AB, Leshin B, McMichael A. Characteristics of office-based visits for skin cancer. Dermatologists have more experience than other physicians in managing malignant and premalignant skin conditions. Dermatol Surg. 1998;24:981–985
  9. Carlson JA, Scott D, Wharton J, Sell S. Incidental histopathologic patterns: possible evidence of ‘field cancerization’ surrounding skin tumors. Am J Dermatopathol. 2001;23:494–496
  10. Del Rosso JQ. The use of topical imiquimod for the treatment of actinic keratosis: a status report. Cutis. 2005;76:241–248
  11. Spencer JM, Hazan C, Hsiung SH, Robins P. Therapeutic decision making in the therapy of actinic keratoses. J Drugs Dermatol. 2005;4:296–301
  12. Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, et al. Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res. 2004;64:2833–2839
  13. Challacombe JM, Suhrbier A, Parsons PG, Jones B, Hampson P, Kavanagh D, et al. Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate. J Immunol. 2006;177:8123–8132
  14. Hampson P, Wang K, Lord JM. PEP-005. Drugs Future. 2005;30:1003–1005
  15. Anderson L, Welburn P. Maximum tolerated dose of PEP005 Topical Gel for the treatment of actinic keratosis [ADA Poster P1503]. Paper presented at: American Academy of Dermatology 2007 Summer Meeting, August 1-5, 2007; New York, NY.
  16. Siller G, Gebauer K, Welburn P. Treatment of actinic keratosis with PEP005 Topical Gel [AAD Poster P1900]. Paper presented at: American Academy of Dermatology 2006 Summer Meeting, July 26-30, 2006; San Diego, CA.
  17. Jorizzo J, Dinehart S, Matheson R, Moore JK, Ling M, Fox TL, et al. Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head. J Am Acad Dermatol. 2007;57:265–268
  18. Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol. 2004;50:714–721
  19. Korman N, Moy R, Ling M, Matheson R, Smith S, McKane S, et al. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol. 2005;141:467–473
  20. Jorizzo J, Weiss J, Furst K, VandePol C, Levy SF. 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;140:813–816
  21. Loven K, Stein L, Furst K, Levy S. Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. Clin Ther. 2002;24:990–1000
  22. 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;6:144–147
  23. Fariba I, Ali A, Hossein SA, Atefeh S, Atarzadeh Behbahan SA. Efficacy of 3% diclofenac gel for the treatment of actinic keratoses: a randomized, double-blind, placebo controlled study. Indian J Dermatol Venereol Leprol. 2006;72:346–349
  24. Wolf JE, Taylor JR, Tschen E, Kang S. Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol. 2001;40:709–713
  25. Rivers JK, Arlette J, Shear N, Guenther L, Carey W, Poulin Y. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol. 2002;146:94–100
  26. Wellburn P, Dosik JS. Skin sensitization potential of PEP005 topical gel. Presented at: 65th Annual AAD Meeting; February 1-5, 2007; Washington, DC.

 Funding sources: Peplin Ltd, for Clinical Research and as a member of the Scientific Advisory Committee.

 Disclosure: Dr Anderson was a clinical investigator, chairs a dose escalation committee on an unrelated clinical trial, and serves on an advisory board for Peplin Ltd. Ms Katsamas is an employee of Peplin Ltd. Dr Ling received a research grant for clinical studies from Graceway and Actavis. Dr Schmieder served as an investigator for Peplin, Genentech, Novum, and Astellas. Dr Werschler has served as an investigator for Peplin, Graceway, and Valent/ICN and as an investigator, speaker, consultant, and on an advisory board for Dermik. Drs Stough and Tschen report no conflicts of interest.

 A list of all clinical investigators participating in the study is found at the end of the article.

PII: S0190-9622(09)00033-4

doi: 10.1016/j.jaad.2009.01.008

Journal of the American Academy of Dermatology
Volume 60, Issue 6 , Pages 934-943 , June 2009

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