Researching New Treatments for Canine Hemangiosarcoma

06/05/2020
Author: Sharon M. Albright, DVM, CCRT

Hemangiosarcoma is a deadly cancer of the cells that line blood vessels. It most commonly affects the spleen, heart, and skin of dogs. While skin tumors can often be cured by surgical removal, the prognosis for splenic hemangiosarcoma is poor due to microscopic spread of cancer cells throughout the body by the time it is diagnosed. The average survival time for dogs with splenic hemangiosarcoma following surgical removal of the spleen (splenectomy) is only 2 months, and only 10% of these dogs will be alive one year following surgery. The average survival time increases to six to eight months when dogs are treated with splenectomy and chemotherapy. There has been little improvement in our ability to treat canine hemangiosarcoma over the past several decades. However, there is reason for hope. The AKC Canine Health Foundation (CHF) and its donors have supported studies on a promising new treatment for this dreaded cancer.

Dr. Daniel Vallera, a professor at the University of Minnesota Medical School and Masonic Cancer Center, invented a drug known as eBAT, which stands for epidermal growth factor (EGF) bispecific ligand targeted angiotoxin. The goal of using targeted toxins is to selectively kill tumor cells, while minimizing damage to normal cells. eBAT is particularly suited to treat hemangiosarcoma because it targets tumor cells and the blood vessels that support them. With CHF funding (Grant 01889-G: Innovations in Prevention, Diagnosis, and Treatment of Cancer - Goldens Lead the Way and Grant 02234-MOU: A Novel Approach for Prevention of Canine Hemangiosarcoma), a research team at the University of Minnesota College of Veterinary Medicine studied the use of eBAT to treat canine splenic hemangiosarcoma.

Results from the first clinical trial were published in the journal Molecular Cancer Therapeutics.1 Twenty-three dogs participated and received eBAT via slow intravenous infusion every other day for three treatments after splenectomy and before starting standard chemotherapy with doxorubicin. Chemotherapy in this trial was delayed until three weeks after the first dose of eBAT. Results showed that eBAT was safe and potentially effective against canine hemangiosarcoma. The six-month survival rate improved from less than 40% in a comparison group to approximately 70% in the treatment group (meaning 70% of dogs were still alive 6 months after diagnosis). Six dogs lived more than 450 days (approximately 15 months). Unfortunately, half of the dogs eventually developed metastatic disease. This left investigators wondering if modifying the dosing schedule for eBAT could improve clinical outcomes.

A second clinical trial was conducted using eBAT to treat splenic hemangiosarcoma with a modified dosing schedule. For this trial, dogs received three cycles of eBAT (three rounds of three every other day infusions) and chemotherapy with doxorubicin was started on day 8 of the trial. Results recently published in Veterinary and Comparative Oncology2 showed that the increased dosing of eBAT resulted in more and worse adverse effects such as low blood pressure, liver enzyme elevation, vomiting, and allergic reaction. There was also no statistically significant improvement in survival time. Additional study is needed to answer questions such as how many cycles of eBAT treatment offer the best outcome and what is the optimal timing interval between eBAT dosing and starting standard chemotherapy.

While there are many variables to explore while refining the use of eBAT to treat splenic hemangiosarcoma in dogs, CHF and its donors are committed to supporting promising studies like these so that veterinarians may soon have new and more effective tools to treat this deadly cancer. CHF is also supporting a multi-institution clinical trial (CHF Grant 02534: Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma) studying if the drug propranolol, commonly used to treat heart disease, is helpful in treating canine hemangiosarcoma. Propranolol has been associated with better outcomes when used to treat human angiosarcoma, a cancer similar to hemangiosarcoma. This collaborative approach examining potential treatment tools for dogs and humans with cancer will speed our progress and improve outcomes for both species.

Learn more and join CHF in our fight against hemangiosarcoma at akcchf.org/hemangiosarcoma.

 

References:

  1. Borgatti, A., Koopmeiners, J. S., Sarver, A. L., Winter, A. L., Stuebner, K., Todhunter, D., … Vallera, D. A. (2017). Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR. Molecular Cancer Therapeutics16(5), 956–965. 
    https://doi.org/10.1158/1535-7163.MCT-16-0637
  2. Borgatti, A., Fieberg, A., Winter, A. L., Stuebner, K., Taras, E., Todhunter, D., Masyr, A., Rendhal, A., Vallera, D. A., Koopmeiners, J. S., & Modiano, J. F. (2020). Impact of Repeated Cycles of EGF Bispecific Angiotoxin (eBAT) Administered at a Reduced Interval from Doxorubicin Chemotherapy in Dogs with Splenic Hemangiosarcoma. Veterinary and Comparative Oncology
    https://doi.org/10.1111/vco.12590

 

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