Clinical update of Ad-p53 gene therapy for lung cancer.

These preliminary Phase I and II gene therapy trials in NSCLC have demonstrated that Ad-p53 gene transfer is associated with low toxicity and evidence of antitumoral activity at the locoregional site. Effort to enhance antitumoral efficacy with chemotherapy and radiation therapy have not increased Ad-p53 toxicity and appear to be feasible. Randomized Phase III studies are now needed to determine the potential of Ad-p53 to improve overall survival in selected subsets of NSCLC patients. Future gene therapy research is required to develop systemic delivery systems and to overcome p53 tumor resistance. It is hoped that these efforts will ultimately lead to a novel mode of therapy to complement conventional chemotherapy, radiation therapy, and surgical treatment strategies.