Gene therapy for esophageal cancer

Esophageal cancer is a highly malignant disease in which progression is observed in most patients even at the first medical examination. Neoadjuvant cytoreduction treatments are frequently used for the purpose of tumor down-staging, increasing the resection rate, and possibly improving survival. Although combination therapy with radiation and anticancer agents is available, no satisfactory treatment regimen has yet been established due to the development of resistance. Based on the concepts of genetic alteration in carcinogenesis, cancer gene therapy has been developing rapidly. We previously reported the growth inhibitory effect of adenovirus-mediated wild-type p53 gene transfer into esophageal squamous carcinoma cell lines. After extensive preclinical study of p53 gene therapy in vitro and in vivo, we are conducting a phase I/II clinical trial. The target of this trial is patients with unresectable esophageal cancer resistant to chemoradiotherapy. As of December 1, 2001, 8 candidates had been admitted to our hospital. After extensive examination, 4 patients were enrolled in this trial. After giving informed consent, the first patient received injections of Ad5 CMV-p53 on December 19, 2000. No serious adverse events have occurred so far in these patients, and the trial has been conducted safely.