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.

A survey of evidence in the Journal of Veterinary Internal Medicine oncology manuscripts from 1999 to 2007.

OBJECTIVES: To survey and monitor trends in evidence for oncology manuscripts published in the Journal of Veterinary Internal Medicine (JVIM) between 1999 and 2007 based on an evidence-based medicine (EBM) standard. METHODS: All veterinary oncology-related articles published in JVIM and 7 other high-impact journals from 1999 to 2007 were collected by database searches. Relevant manuscripts then were characterized including investigator affiliation, subject matter investigated, retrospective or prospective study design, manuscript type, and classifications of manuscripts using an EBM standard. RESULTS: A total of 172 relevant veterinary oncology manuscripts were identified in JVIM between 1999 and 2007. The proportion of oncology manuscripts published each year rose with the total number of manuscripts published in JVIM (mean, 13%; range, 8-15%). The author affiliations and subject matter were similar during this evaluation period. Case series represented the most common manuscript type (40%). With the exception of a progressive increase in prospective manuscripts and a reduction in case reports, no significant changes in the classification of manuscripts using EBM standards were seen. During this same period, veterinary oncology manuscripts published in 7 high-impact journals were associated with higher standards of evidence including prospective studies and randomized trials. CONCLUSIONS: The standards of evidence for veterinary oncology manuscripts published in JVIM have remained static between 1999 and 2007. This survey provides an informative benchmark for the state of evidence in previous JVIM oncology manuscripts and may be useful in identifying specific opportunities that may raise the standards of evidence in future publications in JVIM.