Treatment of multiple synchronous canine mast cell tumours using intratumoural tigilanol tiglate.

Mast cell tumours (MCTs) are common canine skin neoplasia. While they generally occur as single tumours, multiple synchronous MCTs (msMCTs) of de novo/non-metastatic origin are reported in a proportion of the patient population. Where there is no evidence of metastasis or lymphatic spread, MCTs are effectively controlled by surgery and other local therapies. However, treatment of de novo msMCTs can be more challenging, especially when they occur in surgically difficult locations. Here, we report the use of tigilanol tiglate, a novel small molecule registered as a veterinary pharmaceutical for the local treatment of non-metastatic MCTs, in the treatment of patients with msMCTs presenting at three Australian specialist referral centres. We also present a meta-analysis of the literature to provide a better understanding of the prevalence of canine msMCTs. Notably, nine patients with a total of 32 MCTs were treated during the study. A complete response was recorded in 26 (81%) of the individual MCTs on Day 28 after a single tigilanol tiglate injection. Of the 6 initially non-responsive MCTs, one achieved a complete response after a further tigilanol tiglate treatment. A complete response was reported at 6 months in all 22 of the tumours that were evaluable and that had recorded a complete response at Day 84. For the literature meta-analysis, 22 studies were found with prevalence estimates of msMCTs ranging from 3 to 40%; when combined, these studies yielded 3,745 patients with a prevalence of 13% (95% CI 10; 16). Overall, the results demonstrate the utility of intratumoural tigilanol tiglate as an option for the treatment of multiple MCTs where multiple surgical resections would have been required.

Intratumoural Treatment of 18 Cytologically Diagnosed Canine High-Grade Mast Cell Tumours With Tigilanol Tiglate.

Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT. The TT dose was based on tumour volume (0.5 mg TT/cm3 tumour volume) and delivered intratumourally using a Luer lock syringe and a fanning technique to maximise distribution throughout the tumour mass. Efficacy was assessed on the presence/absence of a complete response (CR) to therapy at days 28 and 84 using response evaluation criteria in solid tumours (RECIST). For dogs not achieving a CR after 28 days, the protocol was repeated with a second intratumoural TT injection. Ten out of 18 dogs (56%) in this study achieved and maintained a CR to at least 84 days after their first or second treatment. Six patients were alive and available for evaluation at 2 years, three of those were recurrence free, and a further three patients were recurrence free following a second treatment cycle. Tigilanol tiglate shows efficacy for local treatment of HGMCT, with higher efficacy noted with a second injection if a CR was not achieved following the first treatment. In the event of treatment site recurrence (TSR), the tumour may be controlled with additional treatment cycles. Tigilanol tiglate provides an alternative local treatment approach to dogs with HGMCT that would either pose an unacceptable anaesthetic risk or the tumour location provides a challenge when attempting surgical excision.

Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate.

BACKGROUND: Tigilanol tiglate (TT) is a novel small molecule for intratumoral treatment of nonmetastatic mast cell tumors (MCTs) in dogs. In a randomized controlled clinical study, 75% of dogs that received a single TT treatment achieved complete resolution of the MCT by 28 days, with no recurrence in 93% of dogs at 84 days. Critical to TT's efficacy was the area of the wound (tissue deficit) after slough of the necrotic tumor relative to pretreatment tumor volume. OBJECTIVES: To analyze data collected during the previous study to (a) describe wounds after slough of treated MCTs and (b) identify determinants of wound area and speed of wound healing. METHODS: Wound presence, condition, and area were determined from clinical records of 117 dogs over 84 days after a single intratumoral TT treatment. RESULTS: Tumor slough occurred 3 to 14 days after treatment, exposing granulation tissue in the wound bed. Wound area after tumor slough in general was related to pretreatment tumor volume, with maximal recorded wound area fully evident in 89% of dogs by day 7. In dogs achieving complete tumor resolution, all wounds were left to heal by secondary intention. Bandaging and other wound management interventions only were required in 5 dogs. Time to healing (ie, full re-epithelialization of treatment site) depended on wound area and location on the body, with most wounds being fully healed between 28 and 42 days after treatment. CONCLUSIONS: Wound area and healing after slough of TT-treated tumors follow a consistent clinical pattern for most dogs.

Recurrence-free interval 12 months after local treatment of mast cell tumors in dogs using intratumoral injection of tigilanol tiglate.

BACKGROUND: Tigilanol tiglate (TT) is a novel small molecule approved by the European Medicines Agency for intratumoral treatment of mast cell tumors (MCTs) in dogs. In a randomized controlled clinical efficacy and safety study in the United States, 85 of 116 dogs that received a single TT injection achieved complete response (CR) of the treated MCT by day 28. OBJECTIVE: To evaluate the durability of the TT treatment response achieved at day 28 in the U.S. study by assessing MCT recurrence at the treatment site 6 and 12 months after TT administration. ANIMALS: Eighty-five dogs previously treated with TT. METHODS: Dogs that achieved CR at day 28 were assessed retrospectively for the presence or absence of MCT at the treatment site using records from clinical visits and telephone interviews with owners. Dogs unavailable at an assessment time were considered lost-to-follow-up and data for their last assessment used in the final analysis. RESULTS: By 12 months after TT treatment, 64 dogs remained evaluable, with 21 unavailable. Of evaluable patients, 57 (89%) remained tumor free at the treatment site and 7 (11%) had developed recurrence. All recurrences occurred within the first 6 months, predominantly (5/7, 71%) within the first 12 weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Tigilanol tiglate provided a durable long-term local response for the treatment of MCT in dogs.

Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate (EBC-46).

OBJECTIVE: To evaluate the efficacy and safety of tigilanol tiglate (TT) for local intratumoral treatment of mast cell tumors (MCTs) in dogs. METHODS: A randomized controlled clinical study in 2 phases involving 123 dogs with cytologically diagnosed MCT. Phase 1 compared 81 TT-treated dogs with 42 control dogs; phase 2 allowed TT treatment of control dogs and retreatment of dogs that failed to achieve tumor resolution after TT treatment in phase 1. Tigilanol tiglate (1 mg/mL) was injected intratumorally with dose based on tumor volume. Concomitant medications were used to minimize potential for MCT degranulation. Modified response evaluation criteria in solid tumors were used to evaluate treatment response at 28 and 84 days. Adverse events and quality of life were also assessed. RESULTS: A single TT treatment resulted in 75% complete response (CR) (95% confidence interval [CI] = 61-86) by 28 days, with no recurrence in 93% (95% CI = 82-97) of dogs by 84 days. Eight TT-treated dogs that did not achieve CR in phase 1 achieved CR after retreatment, increasing the overall CR to 88% (95% CI = 77-93). Control dogs had 5% CR (95% CI = 1-17) at 28 days. Wound formation after tumor slough and wound size relative to tumor volume were strongly associated with efficacy. Adverse events typically were low grade, transient, and directly associated with TT's mode of action. CONCLUSIONS: Tigilanol tiglate is efficacious and well tolerated, providing a new option for the local treatment of MCTs in dogs.