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

Journal of Veterinary Internal Medicine

A.I. Sahora¹  A.W. Rusk²  J. Henkin³  E.M. McKeegan³  Y. Shi³ 

[1] The Oncology Service, LLC, Washington, DC;Animal Clinical Investigation, LLC, Washington, DC;Abbott Laboratories, Abbott Park, IL

关键词: Anti‐angiogenesis;    Case series;    Circulating endothelial cells;    Oncology;    Translational study;   

DOI  :  10.1111/j.1939-1676.2012.00966.x

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2012 by the American College of Veterinary Internal Medicine