Phase I study of repeated intraepithelial delivery of adenoviral p53 in patients with dysplastic oral leukoplakia.

PURPOSE

Advances in tumor biology and clinical trials indicate that p53 transfer is an alternative therapy for head and neck squamous cell carcinoma. The aim of this phase I clinical trial is to evaluate the feasibility, safety, and biologic activity of multiple intraepithelial injections of recombinant adenovirus (rAd)-p53 in patients with dysplastic oral leukoplakia (OLK), the most common precursor of the oral squamous cell carcinoma.

PATIENTS AND METHODS

Eighteen Chinese patients clinically and histopathologically diagnosed as having dysplastic OLK were recruited for this study. On a 15-day cycle, intraepithelial injections of rAd-p53 were administered once every 3 days at dose levels of 1 x 10(8) virus particles/cm(2). During treatment, patients were monitored for adverse events, and enzyme-linked immunosorbent assay was used to detect the serum antiadenoviral immunoglobulin (Ig) G/IgM. Incisional biopsies were performed 24 to 48 hours after the last injection, and immunohistochemistry was used to examine the protein expression of p53, p21, and bcl-2. The patients were followed up for 6 months to observe the initial clinical effect.

RESULTS

All 18 patients received a total cycle without dose-limiting toxicity, and administration was feasible and well tolerated. Adenovirus IgG/IgM turned from negative to positive after the 4 injections with rAd-p53. After treatment, p53 protein expression and p21 protein expression were significantly enhanced (100% and 89.9%, respectively), yet bcl-2 protein presented low expression (16.7%). During the treatment and follow-up, 13 patients (72.2%) showed a clinical response to treatment.

CONCLUSIONS

Intraepithelial injections of Gendicine (SiBiono GeneTech, Shenzhen, China) were safe, feasible, and biologically active for patients with dysplastic OLK. It may be a promising treatment for OLK.