A Pilot Study to Evaluate the Tolerability and Efficacy of Temozolomide in Combination with Doxorubicin for the Adjuvant Treatment of Canine Splenic Hemangiosarcoma
Fellow: Skylar Sylvester
Mentor: Cheryl Balkman
DESCRIPTION (provided by applicant):
Hemangiosarcoma is the most common splenic cancer diagnosed in dogs. The standard of care treatment is splenectomy (surgery) followed by doxorubicin chemotherapy, but long-term survival remains poor.
The combination of dacarbazine-doxorubicin adjuvant chemotherapy improved upon these survival outcomes in a recent study, but the clinical use of dacarbazine has been limited given the logistics of its administration and potential for toxicity. Dacarbazine is administered intravenously as a long infusion over 8 hours or as a bolus by slow IV injection once daily for 5 consecutive days every 3 weeks; both long infusions and intensive daily intravenous chemotherapy protocols pose logistical and financial challenges for pet owners and veterinarians, as well as increased risk to the dog receiving the drug as accidental extravasation may cause severe local irritation and pain. In addition, dacarbazine has been associated with a clinically significant and dose-limiting side effect profile including gastrointestinal tract toxicosis such as nausea, vomiting, and diarrhea, and severe to life-threatening hematologic toxicosis, including neutropenia and thrombocytopenia. Temozolomide, a drug closely related to dacarbazine, appears to be better-tolerated in dogs and its dosing route and schedule is more convenient; owners are able to administer the drug orally at home.
The first step of our research project is to perform a pilot study investigating a combination chemotherapy protocol that is a well-tolerated and commercially-available, but novel for the treatment of splenic HSA. We hypothesize that the addition of an at-home administered oral chemotherapy drug, temozolomide, to standard of care intravenous chemotherapy will improve survival for these dogs and be well-tolerated. Following completion of this pilot study we would like to perform a randomized controlled clinical trial comparing doxorubicin-temozolomide combination chemotherapy to standard of care doxorubicin to further investigate its efficacy in dogs with hemangiosarcoma.