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.