A Phase II Trial of Humanized Anti‐Vascular Endothelial Growth Factor Antibody for the Treatment of Androgen‐Independent Prostate Cancer

Objective: Vascular endothelial growth factor (VEGF) is a glycoprotein that is important in promoting tumor angiogenesis. Recombinant humanized anti (rhuMAb)-VEGF is a humanized murine monoclonal antibody that neutralizes VEGF activity and has shown promise in animal tumor models. Methods: To evaluate the efficacy and safety of single-agent rhuMAb VEGF in metastatic androgen-independent prostate cancer (AIPC), we treated 15 patients with 10 mg/kg rhuMAb VEGF every 14 days for six infusions (one cycle), followed by additional treatment for selected patients who had a response or were stable. Results: After one cycle, none of the 15 patients who were evaluable for tumor response had an objective complete or partial response. Three possible mixed responses were observed. No patient achieved a >50% decrease in serum prostate specific antigen (PSA) level after one cycle. Four patients (27%) had a PSA decline of 50%. The median time to objective progression was 118 days, and the median time to PSA progression was 57 days. Toxicity was generally mild, with asthenia present in 6 (40%) of 15 patients. Severe hyponatremia developed in two patients, although the association with rhuMAb VEGF was unclear. Conclusions: We concluded that single-agent rhuMAb VEGF in this dose and with this schedule did not produce significant objective responses in patients with AIPC. Further development of this agent in patients with prostate cancer should focus on earlier stage disease or should evaluate it in combination with other therapies.