Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
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Retrospective evaluation of toceranib phosphate (Palladia) for treatment of different tumor types in 31 dogs

  • Choi, Seo-In (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University) ;
  • Nam, Ye-Lim (Haemaru Referral Animal Hospital) ;
  • Kim, Jin-Kyoung (Haemaru Referral Animal Hospital) ;
  • Park, Hyung-Jin (Sungsim Animal Medical Center) ;
  • Song, Kun-Ho (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University) ;
  • Seo, Kyoung Won (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University)
  • Received : 2020.12.18
  • Accepted : 2021.02.25
  • Published : 2021.03.31
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Abstract

The purpose of this retrospective study was to provide additional data on the use of toceranib in a wide variety of tumor types in small breed dogs, especially < 8 kg (except 5 dogs). This was a retrospective study of 31 dogs with malignant tumors treated with a 2.5 mg/kg median dose of toceranib (Palladia; Zoetis, USA) on a Monday-Wednesday-Friday schedule. Clinical benefit was observed in 13 of 15 dogs (86.7%, 3 with complete response, 4 with partial response, 6 with stable disease) with gross disease. Distant metastasis, response to treatment, and treatment setting were significantly associated with survival time. Negative prognostic factors were multiple chemotherapy and distant metastasis (affecting progression-free survival [PFS]), surgery, regional enlarged lymph nodes, underlying disease, and toxicity (affecting median survival time [MST]). Positive prognostic factors were epithelial and round cell tumor (affecting PFS), epithelial tumor, microscopic disease, no evidence of disease response, and stable disease (MST). In conclusion, a clinical benefit from toceranib treatment was noted in most of the dogs with gross disease in our study. This study suggested that the toceranib is probably selective treatment to various tumor types in small breed dogs.

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References

  1. Pryer NK, Lee LB, Zadovaskaya R, Yu X, Sukbuntherng J, Cherrington JM, London CA. Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast cell tumors. Clin Cancer Res 2003;9:5729-5734.
  2. Chow LQ, Eckhardt SG. Sunitinib: from rational design to clinical efficacy. J Clin Oncol 2007;25:884-896. https://doi.org/10.1200/JCO.2006.06.3602
  3. Papaetis GS, Syrigos KN. Sunitinib: a multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies. BioDrugs 2009;23:377-389. https://doi.org/10.2165/11318860-000000000-00000
  4. Vail DM, Thamm DH, Liptak JM. Withrow and MacEwen's Small Animal Clinical Oncology. 6th ed. pp. 197-198, Elsevier, St. Louis, 2020.
  5. London CA, Hannah AL, Zadovoskaya R, Chien MB, Kollias-Baker C, Rosenberg M, Downing S, Post G, Boucher J, Shenoy N, Mendel DB, McMahon G, Cherrington JM. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 2003;9:2755-2768.
  6. London CA, Malpas PB, Wood-Follis SL, Boucher JF, Rusk AW, Rosenberg MP, Henry CJ, Mitchener KL, Klein MK, Hintermeister JG, Bergman PJ, Couto GC, Mauldin GN, Michels GM. Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res 2009;15:3856-3865. https://doi.org/10.1158/1078-0432.CCR-08-1860
  7. Shin HR, Kim JS, Kim SM, Song KH, Seo KW. Metronomic chemotherapy with toceranib phosphate for treatment of a chemodectoma in a dog. J Vet Clin 2017;34:43-46. https://doi.org/10.17555/jvc.2017.02.34.1.43
  8. Musser ML, Taikowski KL, Johannes CM, Bergman PJ. Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014-2017). BMC Vet Res 2018;14:272. https://doi.org/10.1186/s12917-018-1597-7
  9. Koshino A, Mauldin GE, Dickinson RM, Mauldin GN. A clinical oncology case report. Can Vet J 2011;52:899-902.
  10. Heaton CM, Fernandes AFA, Jark PC, Pan X. Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs. J Vet Intern Med 2020;34:873-881. https://doi.org/10.1111/jvim.15706
  11. London C, Mathie T, Stingle N, Clifford C, Haney S, Klein MK, Beaver L, Vickery K, Vail DM, Hershey B, Ettinger S, Vaughan A, Alvarez F, Hillman L, Kiselow M, Thamm D, Higginbotham ML, Gauthier M, Krick E, Phillips B, Ladue T, Jones P, Bryan J, Gill V, Novasad A, Fulton L, Carreras J, McNeill C, Henry C, Gillings S. Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours. Vet Comp Oncol 2012;10:194-205. https://doi.org/10.1111/j.1476-5829.2011.00275.x
  12. de Vos J, Ramos Vega S, Noorman E, de Vos P. Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib. Vet Comp Oncol 2012;10:206-213. https://doi.org/10.1111/j.1476-5829.2011.00292.x
  13. Heishima K, Iwasaki R, Kawabe M, Murakami M, Sakai H, Maruo K, Mori T. Short-term administration of single-agent toceranib in six cases of inoperable massive canine hepatocellular carcinoma. J Am Anim Hosp Assoc 2019;55:35-41. https://doi.org/10.5326/jaaha-ms-6788
  14. Sheppard-Olivares S, Bello NM, Wood E, Szivek A, Biller B, Hocker S, Wouda RM. Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009-2018). Vet Comp Oncol 2020;18:519-527. https://doi.org/10.1111/vco.12571
  15. Koltai Z, Szabo B, Jakus J, Vajdovich P. Tyrosine kinase expression analyses in canine mammary gland tumours: a pilot study. Acta Vet Hung 2018;66:294-308. https://doi.org/10.1556/004.2018.027
  16. Laver T, London CA, Vail DM, Biller BJ, Coy J, Thamm DH. Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma. Vet Comp Oncol 2018;16:E23-E29. https://doi.org/10.1111/vco.12328
  17. Kim C, Matsuyama A, Mutsaers AJ, Woods JP. Retrospective evaluation of toceranib (Palladia) treatment for canine metastatic appendicular osteosarcoma. Can Vet J 2017;58:1059-1064.
  18. Berger EP, Johannes CM, Jergens AE, Allenspach K, Powers BE, Du Y, Mochel JP, Fox LE, Musser ML. Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs. J Vet Intern Med 2018;32:2045-2053. https://doi.org/10.1111/jvim.15335
  19. Yamazaki H, Miura N, Lai YC, Takahashi M, Goto-Koshino Y, Yasuyuki M, Nakaichi M, Tsujimoto H, Setoguchi A, Endo Y. Effects of toceranib phosphate (Palladia) monotherapy on multidrug resistant lymphoma in dogs. J Vet Med Sci 2017;79:1225-1229. https://doi.org/10.1292/jvms.16-0457
  20. Bernabe LF, Portela R, Nguyen S, Kisseberth WC, Pennell M, Yancey MF, London CA. Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose. BMC Vet Res 2013;9:190. https://doi.org/10.1186/1746-6148-9-190
  21. Nguyen SM, Thamm DH, Vail DM, London CA. Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document. Vet Comp Oncol 2015;13:176-183. https://doi.org/10.1111/vco.12032
  22. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.1. Vet Comp Oncol 2016;14:417-446. https://doi.org/10.1111/vco.283
  23. Elliott JW, Swinbourne F, Parry A, Baines L. Successful treatment of a metastatic, gastrointestinal stromal tumour in a dog with toceranib phosphate (Palladia). J Small Anim Pract 2017;58:416-418. https://doi.org/10.1111/jsap.12657
  24. Hong H, Lim S, Shin HR, Choi H, Lee H, Song KH, Seo KW. Metronomic chemotherapy with toceranib phosphate for a disseminated histiocytic sarcoma in a Miniature Schnauzer dog. J Vet Clin 2017;34:441-444. https://doi.org/10.17555/jvc.2017.12.34.6.441
  25. Jacobs TM, Poehlmann CE, Kiupel M. Injection-site sarcoma in a dog: clinical and pathological findings. Case Rep Vet Med 2017;2017:6952634.
  26. Frost D, Lasota J, Miettinen M. Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases. Vet Pathol 2003;40:42-54. https://doi.org/10.1354/vp.40-1-42
  27. Patruno R, Marech I, Zizzo N, Ammendola M, Nardulli P, Gadaleta C, Introna M, Capriuolo G, Rubini RA, Ribatti D, Gadaleta CD, Ranieri G. c-Kit expression, angiogenesis, and grading in canine mast cell tumour: a unique model to study cKit driven human malignancies. Biomed Res Int 2014;2014:730246.
  28. Kubo K, Matsuyama S, Katayama K, Tsutsumi C, Yonezawa K, Shimada T, Kotani T, Sakuma S, Ohashi F, Takamori Y. Frequent expression of the c-kit proto-oncogene in canine malignant mammary tumor. J Vet Med Sci 1998;60:1335-1340. https://doi.org/10.1292/jvms.60.1335
  29. de Araujo MR, Campos LC, Ferreira E, Cassali GD. Quantitation of the regional lymph node metastatic burden and prognosis in malignant mammary tumors of dogs. J Vet Intern Med 2015;29:1360-1367. https://doi.org/10.1111/jvim.13576
  30. Baginski H, Davis G, Bastian RP. The prognostic value of lymph node metastasis with grade 2 MCTs in dogs: 55 cases (2001-2010). J Am Anim Hosp Assoc 2014;50:89-95. https://doi.org/10.5326/JAAHA-MS-5997
  31. Yamazaki H, Tanaka T, Mie K, Nishida H, Miura N, Akiyoshi H. Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs. J Vet Intern Med 2020;34:1272-1281. https://doi.org/10.1111/jvim.15768