title: Prospective study of thrombospondin-1 mimetic peptides, ABT-510 and ABT-898, in dogs with soft tissue sarcoma.
abstract: BACKGROUND
  Exposure to anti-angiogenic thrombospondin-1 (TSP-1) mimetic peptides (MPs) has resulted in sporadic anti-tumor activity in humans and dogs.
  
  
  OBJECTIVE
  Novel TSP-1 MPs formulations will be safe, tolerated, and clinically active in soft tissue sarcoma (STS) in dogs.
  
  
  METHODS
  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
  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.
authors: The Oncology Service, LLC, Washington, DC, USA.
authors: A I
authors: AI
authors: Sahora
authors: A W
authors: AW
authors: Rusk
authors: J
authors: J
authors: Henkin
authors: E M
authors: EM
authors: McKeegan
authors: Y
authors: Y
authors: Shi
authors: C
authors: C
authors: Khanna
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D040761:Biomimetic Materials / Q000008:administration & dosage; D001772:Blood Cell Count / Q000662:veterinary; D015331:Cohort Studies; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D011446:Prospective Studies; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D019700:Thrombospondin 1 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C500617:NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt; D009842:Oligopeptides; D019700:Thrombospondin 1; C554676:acetyl-glycyl-valyl-allo-isoleucyl-seryl-glutaminyl-isoleucyl-arginyl-prolyl-cysteinamide