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

A. I. Sahora, A. W. Rusk*, J. Henkin, E. M. McKeegan, Y. Shi, C. Khanna

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1169-1176
Number of pages8
JournalJournal of Veterinary Internal Medicine
Volume26
Issue number5
DOIs
StatePublished - Sep 2012

Keywords

  • Anti-angiogenesis
  • Case series
  • Circulating endothelial cells
  • Oncology
  • Translational study

ASJC Scopus subject areas

  • veterinary(all)

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