Dogs receiving concurrent medications with the potential Navitoclax clinical trial to alter gastrointestinal toxicosis, such as prednisone or nonsteroidal anti-inflammatory drugs, were excluded unless they had received this medication for a minimum of 2 weeks (1 week for prednisone) before scheduled doxorubicin administration with no reported gastrointestinal adverse effects, and they were anticipated to stay on these medications for the duration of the study period. Dogs with gastrointestinal tract involvement, suspicion of

gastrointestinal ulceration or brain metastasis, or pre-existing chronic gastrointestinal diseases such as inflammatory bowel disease or pancreatic insufficiency were also excluded. All included dogs were intended to receive two doses of doxorubicin at either 30 mg/m2 or 1 mg/kg as is standard of care, depending on patient weight. Doxorubicin treatments were administered at least 3 weeks apart. Dogs check details that remained on the study for their second doxorubicin treatment received the same total milligram dose as the first treatment. Doxorubicin was administered as a 20-minute IV infusion. Pre-medication was given as is standard at UC Davis at least 30 minutes

before doxorubicin and included dexamethasone (0.2 mg/kg, IV) for dogs not receiving Phosphatidylinositol diacylglycerol-lyase oral prednisone and diphenhydramine (2 mg/kg, IM or subcutaneously [SQ]) for all dogs. At the time of enrollment, dogs were randomized into one of two feeding protocols (A or B). Randomization was performed by selecting a blank envelope containing the dog’s assignment from a shuffled pile. A crossover design was used such that dogs in group A were fed normally before their first dose of doxorubicin and then fasted for their second dose. Conversely, dogs randomized to group B were fasted for their first dose and then fed normally before their second dose. When dogs

were scheduled to fast, no food was given for 24 hours beginning at 6 P.M. the night before doxorubicin administration. All dogs were treated within an hour before or after 12 P.M., and the time of infusion was recorded. A time discrepancy of less than 2 hours between each of the treatments for each dog was necessary for inclusion in the study. A CBC with differential counts was scheduled 7 to 10 days after each dose of doxorubicin. Additional hematologic and biochemical parameters on each patient were measured throughout the study as clinically indicated (CBC, chemistry panel, and urinalysis). Concomitant medications for supportive care or other ongoing medical conditions were allowed for patients enrolled in the study except for prophylactic antiemetic or antidiarrheal drugs.