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Dermatologie 16. November 2010

From weed to cancer cure

An Australian discovery

The sap from Euphorbia Peplus, a member of the Euphorbiaece species has been used as an ancient medicinal remedy for centuries to treat cancer and warts from the time of Hippocrates 400 BC. More recently, this plant known as Petty Spurge, radium weed or cancer weed, has been used in the treatment of basal cell carcinoma and actinic keratoses. Several therapies are available for BCC and AK, however their limitations, most notably relating to prolonged treatment schedules, treatment-related pain or discomfort and poor cosmetic outcomes, have stimulated interest in the development of new therapies.


In 1999, a formal, EC approved, open design, pilot clinical trial was completed using the raw sap of E. peplus to treat a range of difficult to treat non-melanoma skin cancers and AK’s. A total of 61 clinically or histologically diagnosed lesions were treated: 28 basal cell carcinomas, 16 intraepidermal carcinomas, 4 squamous cell carcinomas and 12 AK’s. Treatment involved 3 consecutive days application of the raw sap. A complete clinical response rate (CCR) of 88 % was observed (mean 14 month follow-up) after 3 daily applications (6 lesions received a second course of 3 applications) of E. peplus sap. For AK, the CCR was 66 %. This trial confirmed anecdotal observations of the sap’s efficacy.


Following the results of this trial, further research using bio-activity guided fractionation led to the identification of the active principle of E. peplus sap known as ingenol mebutate (PEP005), a multicyclic diterpene ester. The mechanism of action against skin cancer was determined to be novel, involving a direct cytotoxic action (induction of necrosis) and the recruitment of an innate immune response (characterized by neutrophil mediated, antibody-dependent cellular cytotoxicity). A formal development program for ingenol mebutate was initiated, which established a suitable manufacturing process and drug product formulation, and culminated in the filing of an Investigational New Drug application with the FDA in 2004. Between 2004 and 2010, clinical trials using ingenol mebutate gel were conducted, resulting in the completion of the phase II and III program. Results of these trials will be presented.

The Author
Dr Gregory Siller, M.B.B.S. (Qld) F.A.C.D.
Central Brisbane Dermatology
9th Floor, Silverton Place
101 Wickham Terrace
Brisbane, Qld 4000
Fax: ++61/7/3831 4387

Greg Siller, Brisbane, Australia, Wiener Medizinische Wochenschrift Skriptum 11/2010

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