Abstract
Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs and wide surgical resection is the current first-line treatment. However, recurrence is common and often requires more specialist and expensive therapies. Tigilanol tiglate is a novel small molecule drug delivered by intratumoral injection that is currently under development to provide a new option for treating MCT. The aim of this study was to characterize a safe and effective dose of tigilanol tiglate for canine MCT and to gather preliminary data on the drug's pharmacokinetics. A multicenter, open-label, uncontrolled, non-randomized, dose de-escalation design was used. Eligibility was MCT stage I/IIa and a tumor size of 0.1–6.0 cm3. Dosing was based on tumor size (50% v/v tumor) and 3 drug concentrations (1.0, 0.5, 0.2 mg/mL) were evaluated. Twenty-seven dogs were treated in 3 dose de-escalation cohorts (10, 10, and 7 dogs, respectively). Efficacy at 21 days was defined using international accepted solid tumor response criteria (RECIST). Greatest efficacy (90% complete response) was observed at the highest drug concentration (1.0 mg/mL) and adverse events were generally low grade, mild and transient, and directly associated with the mode of action of the drug. Hematological and serum biochemistry were generally unremarkable with plasma concentration curves typical of a non-intravenous parenteral medication. Intratumoral treatment of MCT with tigilanol tiglate at a concentration of 1.0 mg/mL was highly efficacious and well-tolerated. These results support the drug's further development for the treatment of MCT and other solid tumors.
Highlights
Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs with an estimated prevalence of 0.25–0.27% [1, 2]
Response to therapy was defined as complete response (CR) resolution of the target tumor, partial response (PR) at least 30% decrease in the longest diameter of target tumor, stable disease (SD) decrease in the longest diameter of the target tumor of
The study was terminated prior to recruiting dogs of cohort 4 (0.05 mg/mL) due to the lower response rate observed in cohort 3 (0.2 mg/mL)
Summary
Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs with an estimated prevalence of 0.25–0.27% [1, 2]. MCTs account for 16–21% of all cutaneous neoplasms in dogs [3, 4]. Up to 27% of dogs with grade 2 MCT will have recurrence following surgery [6]. When surgery is not possible, one or a combination of chemotherapy, radiation therapy or cytoreductive surgery is undertaken [5]. These therapeutic options are often costly and not readily available to dogs in remote regions. The demand for effective alternative or adjunctive therapy to surgery for MCT is high
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