p53 Gene Therapy Shows Activity Against Head and Neck Cancer

Single-agent, intratumoral gene therapy that targetsthe p53 gene is well tolerated and shows evidence of antitumor activity in patients with recurrent squamous cell carcinoma of the head and neck, according to the preliminary results of phase II clinical trials presented at the 35th annual meeting of the American Society of Clinical Oncology (ASCO). The phase II trials were conducted by RPR Gencell, a division of Rhone-Poulenc Rorer. Introgen Therapeutics conducted previous phase I studies of the gene therapy and supplied the therapeutic material.

In total, 170 patients were evaluated in three phase II studies that examined various doses and schedules of the gene therapy. Toxicity associated with the treatment was minimal. The most commonly reported adverse events included pain at the injection site and fever, both of which were manageable and self-limited.

Reengineered Adenovirus Used as Treatment Vector

In the largest of the studies, 106 patients with recurrent squamous cell carcinoma of the head and neck received a single-agent treatment with RPR/INGN 201, a common adenovirus. The adenovirus was reengineered to be nonreplicating and to deliver a normal p53 gene into the cancer cells. In more than 40% of the patients, tumors had progressed despite treatment with one or more combinations of chemotherapy and/or repeat radiation therapy. In this study, gene therapy was administered following one of two schedules, and 90 of the 106 patients were evaluable for antitumor activity.

Of these 90 evaluable patients, 5 (6%) had a complete or partial response. In addition, 18 (20%) patients achieved tumor growth stabilization that was maintained from 2 to 11 months.

Data collected to date from the other two trials also show antitumor activity at the two doses studied and across three dosing schedules (ranging from 1 to 6 days per month). Exploratory analyses have suggested better antitumor activity in patients with tumors less than 7.5 cm, and a benefit from a more frequent or intense administration of the p53 gene.

Possible Impact on Survival

Despite the lack of a control group, the observed 7-month median overall survival time appears to be meaningful.
 “The median survival time of patients with recurrent ead and neck cancer under currently available treatments is, unfortunately, quite short, often less than 6 months. No treatment to date has ever shown an improvement in these statistics. The fact that this novel approach, as a single agent, seems to show some therapeutic benefit beyond the 6-month mark is good news,” said John Nemunaitis, MD, regional director of PRN Research Incorporated, director of Texas Oncology Physician Association Research, and study investigator. “We look forward to moving into phase III trials to further test the efficacy of this treatment”