Details

Autor(en) / Beteiligte

• FOX, William D
• HIGGINS, Brian
• MAIESE, Krista M
• DROBNJAK, Marija
• CORDON-CARDO, Carlos
• SCHER, Howard I
• AGUS, David B

Titel

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

Ist Teil von

• Clinical cancer research, 2002-10, Vol.8 (10), p.3226-3231

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (rhuαVEGF) in the treatment of the CWR22R androgen-independent xenograft model of prostate cancer. Experimental Design: rhuαVEGF has previously shown clinical activity in several xenograft cancer models. We administered 5 mg/kg rhuα VEGF i.p. twice weekly as a single agent and together with paclitaxel to established CWR22R xenografts. Results: rhuαVEGF 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 rhuαVEGF 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 rhuαVEGF resulted in greater inhibition of tumor growth than that observed with either agent alone (98% growth inhibition, P = 0.024 versus rhuαVEGF alone and P = 0.02 versus paclitaxel alone). Paclitaxel alone had no antiangiogenic effects at the dosage studied, whereas rhuαVEGF had significant inhibition of angiogenesis, noted by microvessel density and CD34 staining. Conclusions: rhuαVEGF has cytostatic clinical activity in this androgen-independent prostate cancer xenograft model, and the addition of paclitaxel demonstrates increased clinical activity.