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- W2017484966 abstract "Background: Angiotensin‐(1–7) [Ang‐(1–7)] is an endogenous peptide hormone of the renin‐angiotensin system with anti‐proliferative and anti‐angiogenic properties. The primary objective of this study was to establish the recommended phase II dose of Ang‐(1–7) for treating patients with advanced cancer. Secondary objectives were to assess toxicities, pharmacology, clinical responses, and potential biomarkers of anti‐angiogenic effects. Methods: Patients with advanced solid tumors refractory to standard therapy were eligible. Patients were treated with escalating doses of Ang‐(1–7) in cohorts of three patients. Ang‐(1–7) was administered by subcutaneous injection once daily for five consecutive days on a three week cycle. Tumor measurements were performed every two cycles and treatment was continued until disease progression or unacceptable toxicity. Blood samples were obtained for pharmacokinetic and plasma biomarker analyses. Results: Eighteen patients were enrolled. Serious adverse events possibly related to treatment included stroke, reversible cranial neuropathy, and deep vein thrombosis. Other toxicities were mild. One patient developed a 19% reduction in tumor measurements. Three additional patients demonstrated clinical benefit with stabilization of disease lasting more than three months. One patient with stable disease also demonstrated cystic tumor changes, and one patient with stable disease also demonstrated minor PSA reductions after each cycle. In patients with clinical benefit, Ang‐(1–7) administration resulted in a dose‐dependent decrease in plasma placental growth factor (PlGF) (P = .04) on day 1. No change in plasma PlGF occurred in patients without clinical benefit on day 1 (P = .25). On day 5, PlGF levels remained lower in patients with clinical benefit compared to patients without clinical benefit (P = .04). Conclusions: Ang‐(1–7) is a first‐in‐class anti‐angiogenic drug targeting the mas receptor. Clinical benefit is associated with a reduction in plasma PlGF levels following Ang‐(1–7) treatment. The recommended phase II dose is 400 mcg/kg for this administration schedule. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B208." @default.
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- W2017484966 date "2009-12-10" @default.
- W2017484966 modified "2023-09-25" @default.
- W2017484966 title "Abstract B208: Phase I study of angiotensin‐(1–7), an endogenous antiangiogenic hormone: Clinical, pharmacokinetic, and biomarker findings" @default.
- W2017484966 doi "https://doi.org/10.1158/1535-7163.targ-09-b208" @default.
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