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