ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Dog Diseases , Mast Cells , Animals , Dog Diseases/drug therapy , Dogs , Neoplasm Recurrence, Local/veterinary , Surgical Wound Infection/veterinary , Wound HealingABSTRACT
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.
