A phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients with solid tumors.

PURPOSE

The purpose of the current study were to assess the safety and feasibility of repetitive intratumoral administration of E10A, an adenoviral vector encoding the wild-type endostatin gene, to patients with solid tumors, and to evaluate its biologic effect and the pharmacokinetics of endostatin.

METHODS

Patients were treated with escalating doses from 1 x 10(10) VP to 1 x 10(12) VP of E10A intratumorally on days 1 and 8. Patients were assessed for toxicity and viral shedding, and antitumor response was evaluated by imaging techniques and tumor biopsy. Circulating levels of endostatin were examined.

RESULTS

Fifteen patients received 29 injections of E10A. No dose-limiting toxicity was developed, and the maximum tolerated dose had not yet been reached. Fever and local reaction of injection site were common, but rarely severe. Mild and transient hepatotoxicity was observed in one patient. Minor response of injected tumor was achieved and improvement of the control tumor was observed in one patient with nasopharyngeal carcinoma, and tumor necrosis was occurred in two patients. Sustained elevation of serum endostatin levels was detected.

CONCLUSION

Weekly intratumoral injection of up to 1 x 10(12) VP of E10A to patients with solid tumor is a feasible and well-tolerated procedure that exerts mild antitumor effects. A small and sustained elevation of endogenous endostatin in blood possibly has antitumor activity.