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Volume 2016, Article ID 4592768, 7 pages
Clinical Study

Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma

1Department of Medicine, Section of Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA
2Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Winston-Salem, NC, USA
3Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
4Department of Surgical Sciences, Center for Hypertension and Vascular Research, Wake Forest School of Medicine, Winston-Salem, NC, USA
5Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA

Received 25 July 2016; Accepted 20 September 2016

Academic Editor: Shreyaskumar Patel

Copyright © 2016 Paul D. Savage et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7), two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7) was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma) and 19 months (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.