The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma

Abstract

In dogs, inflammatory mammary carcinoma is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Reported median survival time is short, with no effective treatment options. The aims of this prospective, noncontrolled clinical trial were to investigate outcome variables and safety profile of toceranib, thalidomide and piroxicam with or without hypofractionated radiation therapy in dogs with measurable histologically confirmed inflammatory mammary carcinoma that underwent a complete staging. Eighteen dogs were enrolled: 14 received medical treatment, and 4 were treated with hypofractionated radiation therapy and medical therapy. Overall, median time to progression was 34 days and median survival time was 109 days. In dogs treated with medical therapy, overall response rate was 21%, and clinical benefit rate (CBR) was 64%; median time to progression was 28 days and median survival time was 59 days. In dogs receiving medical therapy and undergoing radiation therapy, overall response rate and clinical benefit rate were 100%, with significantly longer time to progression (156 days) and survival time (180 days). Overall, treatment was well tolerated, with mild gastrointestinal and dermatological adverse events. Although the optimal treatment to this disease remains uncertain, the current approach consisting of systemic anti-angiogenic drugs with or without hypofractionated radiation therapy, provided clinical benefit in a significant proportion of dogs and should, therefore, be further explored.

Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009‐2018)

“…Gastrointestinal AEs were the most commonly reported in this population of dogs, which is consistent with previous reports of toceranib administration in dogs 36–49 . No novel AEs were reported in our study.…”

“…Gastrointestinal AEs were the most commonly reported in this population of dogs, which is consistent with previous reports of toceranib administration in dogs. [36][37][38][39][40][41][42][43][44][45][46][47][48][49] No novel AEs were reported in our study. One concern was the development of iatrogenic hypothyroidism.…”

“…Additionally, responses were observed for a spectrum of solid tumour histotypes in a phase 1 study 36 . Subsequent off‐label investigations further supported a role for toceranib in the management of numerous canine malignancies 38–49 . Moreover, the expression of multiple receptor tyrosine kinases (RTKs), including KIT, VEGFR, and PDGFR‐α and ‐β, as well as activation of their downstream effector pathways, has been demonstrated in canine thyroid carcinoma 50–53 …”

“…36 Subsequent off-label investigations further supported a role for toceranib in the management of numerous canine malignancies. [37][38][39][40][41][42][43][44][45][46][47][48][49] Moreover, the expression of multiple receptor tyrosine kinases (RTKs), including KIT, VEGFR, and PDGFR-α and -β, as well as activation of their downstream effector pathways, has been demonstrated in canine thyroid carcinoma. [50][51][52][53] The primary objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both a naïve disease setting and in dogs that received prior therapies.…”

Adjuvant Thalidomide and Metronomic Chemotherapy for the Treatment of Canine Malignant Mammary Gland Neoplasms

“…Recently, a multimodal protocol including toceranib, piroxicam and thalidomide with hypofractionated radiation therapy demonstrated clinical benefit in dogs with inflammatory mammary carcinoma (40); clinical benefit was also described in dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide (41). The addition of continuous thalidomide after surgical excision of splenic hemangiosarcoma in dogs was considered beneficial and suggested as a relevant therapy protocol for the disease (42).…”