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

Hum Gene Ther. 2016 Dec;27(12):1008-1014. doi: 10.1089/hum.2016.043. Epub 2016 Aug 30.

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.

Keywords: cervical cancer; radiotherapy; recombinant adenovirus-p53.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenoviridae / genetics*
  • Adult
  • Aged
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / therapy
  • Combined Modality Therapy
  • Female
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Radiation-Sensitizing Agents / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Safety
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics*
  • Uterine Cervical Neoplasms / mortality*
  • Uterine Cervical Neoplasms / radiotherapy
  • Uterine Cervical Neoplasms / therapy

Substances

  • Radiation-Sensitizing Agents
  • Recombinant Fusion Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53

Associated data

  • ChiCTR/ChiCTR-TRC-08000091