Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer

Purpose: We investigated the safety and pharmacokinetics of a recombinant h uman monoclonal antibody ta vascular endothelial growth factor (rhuMAb VEGF ) in patients with cancer. Patients and Methods Cohorts of patients with metastatic cancer having fail ed prior therapy entered a phase I trial of rhuMAb VEGF administered by a 9 0-minute intravenous infusion at doses from 0.1 to 10.0 mg/kg on days 0, 28 , 35, and 42. Patients underwent pharmacokinetic sampling on day 0 and had serum samples obtained during the subsequent 28 days. Response assessment w as carried out on days 49 and 72. Results.. Twenty-five patients with a median Eastern Cooperative Oncology G roup performance status of 0 were accrued. There were no grade III or IV ad verse events definitely related to the antibody. There were three episodes of tumor-related bleeding. Infusions of rhuMAb VEGF were well tolerated wit hout significant toxicity. Grades I and II adverse events possibly or proba bly related to study drug included asthenia, headache, and nausea. Pharmaco kinetics revealed a linear profile with a half-life of 21 days. There were no objective responses, though 12 patients experienced stable disease over the duration of the study Conclusion: rhuMAb VEGF was safely administered without dose-limiting toxic ity at doses ranging up to 10 mg/kg. Multiple doses of rhuMAb VEGF were wel l tolerated, and pharmacokinetic studies indicate that doses of 0.3 mg/kg h ave a half-life similar to that of other humanized antibodies. Subsequent t rials will explore rhuMAb VEGF alone and in combination chemotherapy. (C) 2 001 by American Society of Clinical Oncology.