Contusugene ladenovec(Introgen Therapeutics, Inc.)

This phase II clinical trial compared the efficacy and safety of two types of treatment in patients with non-small-cell lung cancer (NSCLC) who had previously been treated with chemotherapy. Patients diagnosed with NSCLC (with either measurable or evaluable lesions) and had been treated with chemotherapy were eligible for this study. They were randomly assigned to two groups. The DOCp53 group received trans-tracheal Adp53 injection (1 × 10(12) vp dosage) on day 1 and day 8, as well as docetaxel at 75 mg m(-2) on day 2. The DOC group only received docetaxel at 75 mg m(-2) on day 1. Patients in each group received treatment for two cycles before reevaluation. Between February 2005 and December 2006, 40 patients were recruited for this study. In all, 19 of them were assigned to the DOCp53 group and 21 were assigned to the DOC group. After a mean follow-up of 12 months, the median survival time (MST) was 7.7 months (95% CI, 4.53 to 10.84) for patients in the DOCp53 group and 5.9 months (95% CI, 4.11 to 7.68) in the DOC group (P = 0.44, log-rank test). In the DOCp53 group, two patients with diffuse metastatic disease of lung had partial response (PR) in addition to eight with stable disease (SD). No PR and 13 SD were observed in the DOC group. Toxic reactions that could be attributed to the Adp53 vector were transient fever and limited hemoptysis. For patients with relapsed NSCLC, trans-tracheal injection of Adp53 in addition to docetaxel did not improve overall survival or efficacy. However, direct trans-tracheal injection of Adp53 proved to be a safe procedure, with tolerable levels of toxicity.

Limited options are available for patients with advanced stage head and neck cancer. The p53 gene is known as the “guardian of the genome.” Mutations of the p53 gene predispose to carcinogenesis. The p53 mutations are common in head and neck cancer. Replacement of p53 gene function in preclinical models demonstrates cancer regression and improved survival. Clinical data with an adenoviral based p53 gene delivery product (Advexin) supports safety and clinical response after direct intratumoral injection. We summarize p53‐related therapeutics in this review. © 2010 Wiley Periodicals, Inc. Head Neck, 2011