Multicenter, randomized, double-blinded, placebo-controlled study of rabacfosadine in dogs with lymphoma.

BACKGROUND: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. HYPOTHESIS/OBJECTIVES: To determine the efficacy and safety of RAB in dogs with lymphoma. ANIMALS: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. METHODS: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. RESULTS: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%). CONCLUSIONS AND CLINICAL IMPORTANCE: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo.

Long-term delivery of ivermectin by use of poly(D,L-lactic-co-glycolic)acid microparticles in dogs.

OBJECTIVE: To evaluate the potential utility of poly(D,L-lactic-co-glycolic)acid (PLGA) as a long-acting biodegradable drug delivery matrix for ivermectin used in the prevention of heartworm disease in dogs. ANIMALS: 30 adult female dogs. PROCEDURE: Microparticle formulations containing 25 weight percent (wt%), 35 wt%, and 50 wt% ivermectin were prepared by an oil-in-water emulsion technique with solvent extraction into excess water. A fourth formulation, consisting of a mixture of 15 wt% and 50 wt% ivermectin microparticles, was blended in a 1:1 ratio to result in a 32.5 wt% ivermectin formulation. Formulations were administered once on Day 0 to groups of 6 dogs at a dose of 0.5 mg of ivermectin/kg, s.c. Half of the dogs in each treatment group and 3 untreated control dogs were infected with Dirofilaria immitis larvae 121 and 170 days after treatment. Six months after infection, dogs were euthanatized and necropsies were performed. Pharmacokinetics and efficacy were investigated. RESULTS: Analysis of pharmacokinetic data revealed sustained release of ivermectin during at least 287 days in 3 distinct phases: a small initial peak, followed by release of drug through diffusion, and polymer degradation. Untreated control dogs were all infected with heartworms. Heartworms were not found in any of the dogs in the ivermectin-PLGA treated groups. Adverse clinical signs were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: All formulations were 100% effective in preventing development of adult heartworms. Results indicate that PLGA microparticles are a promising drug delivery matrix for use with ivermectin for the prevention of heartworm disease for at least 6 months after treatment.