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Antiangiogenesis drugs can be difficult to evaluate because they produce disease stabilization rather than tumor regression. Markers of endothelial mass in tumors may be of value to monitor therapy and evaluate such drugs. Soluble domains of the endothelial receptor tyrosine kinases, sTie2 (angiopoietin receptor) and sFlt1 (vascular endothelial growth factor receptor-1) were analyzed by sandwich ELISA in serum samples from 43 patients with advanced renal cancer before and 1 month after antiangiogenic therapy with razoxane. Pretreatment sFlt1 levels were 0.77 ng/ml +/- 0.48 (SD) and sTie2 74.3 ng/ml +/- 15 (SD). Pretreatment sFlt1 levels above the median were associated with a lesser chance of stable disease (P = 0.04) and poorer survival (P = 0.01). Fall of sTie2 on treatment was associated with stable disease (P = 0.05) and improved survival (P = 0.04). The soluble receptors measured weeks before response were assessed and correlated with response and survival, showing they may be useful to monitor and develop antiangiogenic therapy.

Type

Journal article

Journal

Clin cancer res

Publication Date

07/2001

Volume

7

Pages

1992 - 1997

Keywords

Antineoplastic Agents, Binding Sites, Enzyme-Linked Immunosorbent Assay, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Multivariate Analysis, Neovascularization, Pathologic, Prognosis, Proto-Oncogene Proteins, Razoxane, Receptor Protein-Tyrosine Kinases, Receptor, TIE-2, Solubility, Survival Analysis, Treatment Outcome, Vascular Endothelial Growth Factor Receptor-1