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

الملخص EN

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.