Open AccessProspective Study of Thrombospondin‐1 Mimetic Peptides, ABT ‐510 and ABT ‐898, in Dogs with Soft Tissue Sarcoma
Author(s) -
Sahora A.I.,
Rusk A.W.,
Henkin J.,
McKeegan E.M.,
Shi Y.,
Khanna C.
Publication year - 2012
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/j.1939-1676.2012.00966.x
Subject(s) - medicine , tolerability , soft tissue sarcoma , sarcoma , prospective cohort study , bolus (digestion) , thrombospondin 1 , gastroenterology , angiogenesis , pharmacology , pathology , adverse effect
Background Exposure to anti‐angiogenic thrombospondin‐1 ( TSP ‐1) mimetic peptides ( MP s) has resulted in sporadic anti‐tumor activity in humans and dogs. Hypothesis Novel TSP ‐1 MP s 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 MP s in dogs with STS . The most notable activity was achieved with the ABT ‐898 formulations.