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  Table of Contents  
Year : 2015  |  Volume : 52  |  Issue : 2  |  Page : 249-250

Could ingenol mebutate be useful in managing nonmelanoma skin cancers?

1 Department of Pharmacology, S. D. M. College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
2 Department of Dermatology, S. D. M. College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India

Date of Web Publication5-Feb-2016

Correspondence Address:
P R Bhandari
Department of Pharmacology, S. D. M. College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.175820

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How to cite this article:
Bhandari P R, Pai V V. Could ingenol mebutate be useful in managing nonmelanoma skin cancers?. Indian J Cancer 2015;52:249-50

How to cite this URL:
Bhandari P R, Pai V V. Could ingenol mebutate be useful in managing nonmelanoma skin cancers?. Indian J Cancer [serial online] 2015 [cited 2021 Aug 5];52:249-50. Available from: https://www.indianjcancer.com/text.asp?2015/52/2/249/175820


Of all nonmelanoma skin cancers, basal cell carcinoma and squamous cell carcinoma, comprising of 75 and 20%, respectively, are most frequent types of cancer in United States. However, incidence of nonmelanoma skin cancers in India is not known. Actinic keratosis (AK) is the early stage of intraepidermal manifestation of abnormal keratinocyte proliferation with the potential of progression to squamous cell carcinoma (SCC). Cryotherapy, surgery and electrodessication with or without curettage, represent the lesion-directed treatment modalities. Whereas, field-directed treatment modalities include nonablative/ablative laser resurfacing, dermabrasion, chemical peels topical immunomodulators (imiquimod, 5-fluorouracil, diclofenac) and photodynamic therapy. However, topical field therapy currently requires weeks or months of treatment. Hence, there is a need for improved medical approaches to the treatment of actinic keratosis.[1]

For centuries for skin conditions, including warts, corns and cancers of the skin, the sap of Euphorbia peplus [Figure 1], commonly known as 'petty spurge', 'radium weed' or 'milkweed' or “cancer weed” or “wart weed” has been used as a traditional treatment. This plant is native to Europe, West Asia, and North Africa. It is now a common weed in North America, Australia and New Zealand. The prevalent constituents of this plant latex are diterpenes from the Inganen types (ingenol esters) [Figure 2] as well as the tigliane (phorbol esters).[2]
Figure 1: Euphorbia peplus plant

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Figure 2: Chemical structure of ingenol

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Presently topical agents for field therapy of actinic keratoses have single mechanism of action with a drawback that it must be applied for weeks. However, Ingenol mebutate gel, a novel drug for field therapy of actinic keratoses, appears to have a dual mechanism of action: (1) rapid lesion necrosis and (2) specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Due to the rapid destruction of actinic keratosis lesions after application of ingenol mebutate gel, treatment is required for only two or three days. Any residual dysplastic epidermal cells are subsequently targeted by immune-mediated response. Thus, this dual mechanism of action provides efficacy similar to that of current topical agents but with substantially shorter treatment duration.[3]

Ramsay JR et al., demonstrated that complete clinical response rates at one month were 82% for BCC, 94% for intraepidermal carcinomas (IEC) and 75% for SCC.[4] Anderson et al. demonstrated that partial clearance rate (primary efficacy end point) for patients of actinic keratosis treated with ingenol mebutate gel ranged from 56.0 to 75.4% compared with 21.7% for vehicle gel. The complete clearance rate was also significantly higher for patients in the ingenol mebutate gel treatment groups (range: 40.0 to 54.4%) compared with vehicle (11.7%).[5]

Data from clinical studies demonstrate that ingenol mebutate treatment for weeks to months has a favorable safety profile and has not produced any serious adverse events.

Based on available data, ingenol mebutate appears to be as efficacious and safe as other non-surgical modalities. Furthermore, the two to three day course of therapy is an added advantage, thus shortening the treatment duration and improving compliance. More studies need to be conducted in India as well, especially comparing ingenol mebutate with currently available therapies. Additionally, data of long-term safety and recurrence risk too needs to be generated.

  References Top

Amini S, Viera MH, Valins W, Berman B. Nonsurgical innovations in the treatment of nonmelanoma skin cancer. J Clin Aesthet Dermatol 2010;3:20-34.  Back to cited text no. 1
Ogbourne SM, Hampson P, Lord JM, Parsons P, De Witte PA, Suhrbier A. Proceedings of the First International Conference on PEP005. Anticancer Drugs 2007;18:357-62.  Back to cited text no. 2
Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: Rapid lesion necrosis followed by lesion-specific immune response. J Am Acad Dermatol 2012;66:486-93.  Back to cited text no. 3
Ramsay JR, Suhrbier A, Aylward JH, Ogbourne S, Cozzi SJ, Poulsen MG, et al. The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol 2011;164:633-6.  Back to cited text no. 4
Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, et al. Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol 2009;60:934-43.  Back to cited text no. 5


  [Figure 1], [Figure 2]


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