Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

J Vet Intern Med. 2018 Nov;32(6):2045-2053. doi: 10.1111/jvim.15335. Epub 2018 Oct 11.

Abstract

Background: Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting.

Objectives: To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value.

Animals: Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib.

Methods: Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs.

Results: Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs.

Conclusions and clinical importance: Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

Keywords: DOG1; KIT; immunohistochemistry; mutation; progression-free interval; tyrosine kinase inhibitor.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Dog Diseases / diagnosis
  • Dog Diseases / drug therapy*
  • Dog Diseases / pathology
  • Dogs
  • Female
  • Gastrointestinal Neoplasms / diagnosis
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / veterinary*
  • Gastrointestinal Stromal Tumors / diagnosis
  • Gastrointestinal Stromal Tumors / drug therapy
  • Gastrointestinal Stromal Tumors / pathology
  • Gastrointestinal Stromal Tumors / veterinary*
  • Indoles / therapeutic use*
  • Male
  • Mitotic Index / veterinary
  • Prognosis
  • Progression-Free Survival
  • Pyrroles / therapeutic use*
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • toceranib phosphate