Prospective study of thrombospondin-1 mimetic peptides, ABT-510 and ABT-898, in dogs with soft tissue sarcoma.

BACKGROUND: Exposure to anti-angiogenic thrombospondin-1 (TSP-1) mimetic peptides (MPs) has resulted in sporadic anti-tumor activity in humans and dogs. HYPOTHESIS: Novel TSP-1 MPs formulations will be safe, tolerated, and clinically active in soft tissue sarcoma (STS) in dogs. ANIMALS: Sixty-two client-owned dogs with measurable STS were enrolled, excluding hemangiosarcoma. METHODS: A prospective, single agent, multicenter, open-label study assessing ABT-510 bolus, ABT-898 bolus, or ABT-898 depot formulations of TSP-1 in dogs. Endpoints included tolerability, antitumor activity, and the assessment of ability of clinical covariates and circulating endothelial cells (CEC) concentration to predict tumor response. RESULTS: Two non-dose-limiting toxicoses possibly attributed to treatment were observed (keratitis and osteoarthritis). Antitumor activity (10/44 = 23% responses) was observed in study subjects who received treatment for >28 days (n = 44) including both partial (7) and minimal responses (3). Responses were disproportionately seen in dogs receiving ABT-898 formulations (9/28 = 32%) versus those receiving ABT-510 (1/16 = 6%; P < .045). Disease stabilization for >84 days was also documented (8/44 = 18%). Slow rates of tumor progression before study entry correlated with anti-tumor activity in treated dogs, whereas no significant association was found between changes in total CEC concentration and tumor response (P = .28) or time to progression (P = .42). CONCLUSIONS AND CLINICAL IMPORTANCE: Safely achieved antitumor activity was documented with TSP-1 MPs in dogs with STS. The most notable activity was achieved with the ABT-898 formulations.

A randomized trial investigating the efficacy and safety of water soluble micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast cell tumors in dogs.

BACKGROUND: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. HYPOTHESIS/OBJECTIVES: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was µ(p) = µ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). ANIMALS: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. METHODS: Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). RESULTS: Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7). CONCLUSIONS AND CLINICAL IMPORTANCE: Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.