Angiogenesis, the formation of new blood vessel from existing vessels, is essential for tumor
growth and metastasis. Antiangiogenic therapies inhibit the growth of genetically stable
endothelial cells, and most tumors should starve to death with little acquired resistance.
Endostatin has been shown to block endothelial cell proliferation, survival, and migration.
Antitumor activity of endostatin protein has been demonstrated in various murine and human
tumors in animal model studies without any detectable toxicity. Endostatin gene therapy could
directly express the highly bioactive protein in vivo by means of the mechanism of eukaryotic
expression system as post-translational modification and folding, as well as overcoming the
challenge of the long-term storage and the cumbersome daily administration of endostatin
protein.
E10A is a replication-deficient recombinant adenovirus containing a wild-type human
endostatin transgene constructed from serotype 5 adenovirus (Ad5). Preclinical studies
demonstrated that intratumoral injection of E10A provided significant tumor growth inhibition
and sustained elevation of endostatin in blood and tumor tissue in hepatocellular carcinoma,
nasopharyngeal carcinoma, and tongue cancer animal models. A Phase I clinical trial of E10A
we conducted showed that repetitive intratumoral injection of E10A resulted in a small and
sustained elevation of endostatin in blood and had a mild antitumor activities with very
limited toxicity. The major toxicity was transient and manageable fever. A randomized Phase
III trial in nonsmall-cell lung cancer showed endostatin improved response rate and time to
tumor progression in combination to chemotherapy. Therefore, we designed a randomized phase
II trial to explore the safety and effectiveness of E10A combined with chemotherapy in the
treatment of patients with head and neck cancer.