Early-stage skin tumors in horses were reduced in size over 13 weeks through regular application of a cream containing betulinic acid, researchers report.
Melanomas are skin tumors of the pigment-producing melanocytes. Equine melanomas are among the most commonly diagnosed tumors affecting grey horses. Melanocytic tumors progress to malignancy in more than two-thirds of cases.
Previous laboratory work using the naturally occurring betulinic acid, extracted from the bark of some tree species, and its derivative NVX-207 have shown promising results.
Lisa Weber and her fellow researchers have now carried out a feasibility study to gain first insights into the effects and safety of betulinic acid and NVX-207 in 18 Lipizzaner mares with early-stage melanocytic tumors.
The horses were divided into three groups for the 13-week experiment. One group received twice-daily applications of a placebo cream, after which a dressing was applied. The second group was treated the same way, but instead received a cream containing 1% betulinic acid. The third group was treated with 1% NVX-207.
A total of 29 small melanomas were treated in the study: Eight had the placebo cream applied, 12 received the betulinic acid cream, and nine were treated with NVX-207.
Blood tests and general clinical examinations were performed to assess the effects and safety of the medications. The skin around the tumors was also regularly checked.
The topical treatment proved to be convenient and safe, the researchers reported in the journal Animals.
The volumes of the tumors treated with betulinic acid were significantly reduced from day 80 of the 91-day study when compared to tumors treated with the placebo. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance.
Overall, the results suggest a positive treatment effect from topical application of both treatments on equine melanomas toward the end of the treatment period, they said, but the study time period was too short to conclusively prove this.
The findings must be regarded as preliminary, they said, because of the limited group size. The work needs to be replicated in a larger group of horses with modified formulations. “Accordingly, the treatment protocol cannot yet be recommended in its current form.”
The researchers were encouraged by the results.
Discussing their findings, they said: “The topical therapy resulted in part in clinically visible and measurable changes in small melanocytic lesions, which were reflected in skin depigmentation and reduction in tumor diameters and volumes.
“A significant beneficial treatment effect could be shown after treatment with betulinic acid towards the end of the treatment period.”
Although most melanocytic tumors in horses show a slow growth pattern for many years, a significant number are thought to progress to malignancy. “For this reason, and because smaller tumors are easier to treat than large ones, even early (pre-cancerous) stages of equine melanoma should be subjected to therapy.”
They said changes to the test formulation, such as increasing the amount of active ingredient or adding permeation enhancers that transport large amounts of the compound through the fibrous tumor capsule, could also aid tumor volume regression and may reduce treatment time.
The treatment may represent — after modification of the pharmaceutical test formulations — an alternative to the frequently practiced approach of benign neglect of small solitary masses, the study team wrote.
They said further work could lead to an effective, topical and marketable novel drug that helps equine skin cancer patients, reducing the health risks associated with the possible malignant degeneration of the tumors.
The study team comprised Weber, Julien Delarocque, Karsten Feige, Manfred Kietzmann and Jessica Meißner, all with the University of Veterinary Medicine Hannover, Foundation, in Germany; Jutta Kalbitz, with Biosolutions Halle GmbH; Reinhard Paschke, with Biozentrum at Martin-Luther-University Halle-Wittenberg; and and Jessika-M. V. Cavalleri, with the University of Veterinary Medicine Vienna in Austria.
Weber, L.A.; Delarocque, J.; Feige, K.; Kietzmann, M.; Kalbitz, J.; Meißner, J.; Paschke, R.; Cavalleri, J.-M.V. Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses. Animals 2021, 11, 3250. https://doi.org/10.3390/ani11113250
The study, published under a Creative Commons License, can be read here.