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Antibody to Vascular Endothelial Growth Factor Slows Growth of an Androgen-independent Xenograft Model of Prostate Cancer¹

Cedars-Sinai Prostate Cancer Center, Los Angeles, California 90048 [W. D. F., B. H., K. M. M., D. B. A.], and Departments of Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [M. D., C. C-C., H. I. S.]

Purpose: Human tumors are dependent on angiogenesis for growth, and vascular endothelial growth factor (VEGF) is a major regulator of this process. We aimed to study clinical utility of a recombinant humanized monoclonal anti-VEGF antibody (rhuVEGF) in the treatment of the CWR22R androgen-independent xenograft model of prostate cancer.

Experimental Design: rhuVEGF has previously shown clinical activity in several xenograft cancer models. We administered 5 mg/kg rhu VEGF i.p. twice weekly as a single agent and together with paclitaxel to established CWR22R xenografts.

Results: rhuVEGF inhibited established tumor growth by 85% (P < 0.01 for trajectories of the average tumor volumes of the groups) at 3 weeks, but after cessation of rhuVEGF treatment, tumor regrowth ensued. A paclitaxel dosage of 6.25 mg/kg s.c. five times/week slowed tumor growth (72% compared with controls at 3 weeks, P = 0.02). The combination of paclitaxel and rhuVEGF resulted in greater inhibition of tumor growth than that observed with either agent alone (98% growth inhibition, P = 0.024 versus rhuVEGF alone and P = 0.02 versus paclitaxel alone). Paclitaxel alone had no antiangiogenic effects at the dosage studied, whereas rhuVEGF had significant inhibition of angiogenesis, noted by microvessel density and CD34 staining.

Conclusions: rhuVEGF has cytostatic clinical activity in this androgen-independent prostate cancer xenograft model, and the addition of paclitaxel demonstrates increased clinical activity.

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