Prospective Study of Thrombospondin‐1 Mimetic Peptides, ABT‐510 and ABT‐898, in Dogs with Soft Tissue Sarcoma

• Published in: Journal of veterinary internal medicine Vol. 26; no. 5; pp. 1169 - 1176
• Main Authors: Sahora, A.I., Rusk, A.W., Henkin, J., McKeegan, E.M., Shi, Y., Khanna, C.
• Format: Journal Article
• Language: English
• Published: United States 01.09.2012
• Subjects: Angiogenesis Inhibitors - administration & dosage; Animals; Antineoplastic Agents - administration & dosage; Anti‐angiogenesis; Biomimetic Materials - administration & dosage; Blood Cell Count - veterinary; Case series; Circulating endothelial cells; Cohort Studies; Dog Diseases - drug therapy; Dog Diseases - metabolism; Dog Diseases - pathology; Dogs; Female; Male; Oligopeptides - administration & dosage; Oncology; Prospective Studies; Sarcoma - drug therapy; Sarcoma - metabolism; Sarcoma - pathology; Sarcoma - veterinary; Soft Tissue Neoplasms - drug therapy; Soft Tissue Neoplasms - metabolism; Soft Tissue Neoplasms - pathology; Soft Tissue Neoplasms - veterinary; Thrombospondin 1 - metabolism; Translational study
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/j.1939-1676.2012.00966.x

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.