The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel

• DOI: 10.1007/s00280-005-1013-4
• Publication Date: 2005-06-09T09:08:16Z
• Authors: Naoki Agata; Hiroko Nogi; Michael Bamberg; Michael Milhollen; Minying Pu; Steven Weitman; Surender Kharbanda; Donald Kufe
• Keywords: Angiogenesis inhibitor; Clonogenic assay; Combination therapy

The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse human tumor xenografts in mice. The present work has assessed the activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used alone and in combination with docetaxel. The results demonstrate that NM-3 decreases clonogenic survival of NSCLC cells at clinically achievable concentrations. The results also demonstrate that NM-3 is effective in the treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3 potentiated the antitumor activity of docetaxel against NSCLC xenografts without increasing toxicity. Our findings indicate that NM-3 may be effective alone or in combination with docetaxel in the treatment of patients with NSCLC.