Proof of concept for low dose and delayed release of tigilanol tiglate in the treatment of equine sarcoids

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Intra-tumoural administration of tigilanol tiglate has been shown effective in local treatment of cutaneous equine neoplasias. The drug causes rapid oncolysis and tumour slough, but may also be associated with comorbidities in sensitive and/or intricate anatomical sites due to its initial pro-inflammatory mode of action. Here we describe two approaches to optimise and further de-risk treatment of equine sarcoids with tigilanol tiglate, especially in difficult locations. Firstly, we provide preliminary clinical and observational data on the efficacy of low dose administration of tigilanol tiglate (metronomic or single intra-tumoural administration). Secondly, we provide proof of therapeutic concept for tigilanol tiglate eluting calcium sulphate beads by evaluating elution characteristics and assessing clinical efficacy treating equine sarcoids. Clinical efficacy, at substantially lower than previously reported tigilanol tiglate treatment doses, was demonstrated by adopting either a single low-dose or metronomic dosing schedule or an eluting implant. Treatments resulted in complete tumour slough in all instances while evoking a perceived reduction in inflammatory responses compared to the use of previously established higher doses for equine sarcoids. While implanted calcium sulphate beads loaded with cytostatic drugs have been used previously for local treatment of equine neoplasia, their utility for local delivery of tigilanol tiglate has not been explored before. Elution analysis of tigilanol tiglate from 5 and 2.5 mm loaded calcium sulphate beads showed beads eluted ~40% and ~24% of their tigilanol tiglate content in horse serum (HS) with continued release observed from intact beads for at least 4 days. The ease of implanting absorbable tigilanol tiglate loaded calcium sulphate beads, and its clinical efficacy in sarcoid treatment, showed the potential of this approach to eliminate common challenges associated with intra-tumoural injection such as inadvertent diffusion from injection sites or the difficulty injecting fibrous tumours. This contributed to reducing the apparent extent of local inflammatory responses and limiting possible associated morbidities. Apart from mild leukotrichia that developed at some treatment sites, healing and cosmetic outcome was deemed excellent. Ongoing studies evaluating the clinical efficacy and safety of lowered tigilanol tiglate doses in a statistically relevant, representative equine population are required to further develop the reported treatment regimens.