new endogenous antiangiogenic agent in trials

[Lani]

Angiotensin-(1-7) Shows Promise as Anti-Cancer Agent
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Dec 01 - Angiotensin-(1-7), an endogenous antiangiogenic hormone, appears to be an effective treatment for various solid tumors, according to the results of a small study reported in the December 1st issue of Clinical Cancer Research.

Angiotensin-(1-7) has been shown in xenograft models to reduce lung and breast tumor growth, the investigators explain, and previous results suggest that it may inhibit tumor growth by reducing proangiogenic factors and thereby attenuating angiogenesis.

Dr. W. Jeffrey Petty and colleagues from Wake Forest University Health Sciences, Winston-Salem, North Carolina undertook a phase 1 study to establish a recommended dose of angiotensin-(1-7) for treating patients with advanced cancer.

The study enrolled 18 patients, 15 of whom were evaluable for response. All of the patients had advanced solid tumors, most commonly colorectal cancer, that were refractory to standard therapy.

There was no hematologic toxicity associated with angiotensin-(1-7) treatment, and treatment was generally well tolerated.

Three patients experienced serious adverse events possibly related to angiotensin-(1-7), including one with deep vein thrombosis, one with multiple strokes, and one with cranial neuropathy.

Two of these events were in patients treated at the 700 microgram/kg dose, so the researchers determined that the 400 microgram/kg dose (as a daily subcutaneous injection for 5 consecutive days on a 3-week cycle) should be the recommended dose.

One patient receiving the 700 microgram/kg dose for metastatic sarcoma experienced a mixed response and had 10 months of stable disease.

Three additional patients had stabilization of disease lasting beyond 3 months, the authors report.

Placental growth factor levels decreased over time in patients with clinical benefit, but not in patients without clinical benefit, the investigators say.

"Two of the three patients with sarcoma had clinical benefit and a phase II trial has been developed at the Wake Forest University to determine the activity of angiotensin-(1-7) for the treatment of this disease," the researchers say. "Given that antiangiogenic drugs tend to have a broad spectrum of activity, phase II testing in other solid tumors is planned."

Clin Cancer Res 2009;15:OF1-7.