Effect and Safety of Recombinant Adenovirus-p53 Transfer Combined with Radiotherapy on Long-Term Survival of Locally Advanced Cervical Cancer.

ABSTRACT

Detection of exogenous p53 gene and target gene expression in cervical cancer cell lines SiHa and C33A infected by recombinant adenovirus-p53 (rAd-p53) in vitro. The rAd-p53 infection evidently increased the expression of exogenous p53 gene, p21 gene, and Bax gene. The radiosensitization rates of rAd-p53 were 1.19 in SiHa and 1.18 in C33A in vitro. To evaluate the effect and safety of rAd-p53 transfer combined with radiotherapy (RT) in patients with cervical cancer, rAd-p53 transfer combined with radiotherapy (group PRT) in 69 patients with cervical cancer was compared with a control group treated with radiotherapy alone (group RT) in 35 patients with cervical cancer. Patients were intratumorally injected with rAd-p53 (1 × 1012 virus particles) once a week for 6 weeks. Concurrent pelvic RT plus brachytherapy to take point A to 76.0 Gray units (Gy) (range 75-80 Gy). The 5-year overall survival rate of the PRT group was 17.5% higher than that of the RT group (HR = 0.551, 95% CI 0.278-1.095, p = 0.084). The 5-year progress-free survival rate of the PRT group was 17.1% higher than that of the RT group (HR = 0.485, 95% CI 0.234-1.006, p = 0.047). rAd-p53 administration did not increase the adverse events caused by radiotherapy, except for transient fever after rAd-p53 administration. rAd-p53 was safe and biologically active in improving radiotherapeutic survival rates in patients with cervical cancer.