Successful adenovirus-mediated wild-type p53 gene transfer in patients with bladder cancer by intravesical vector instillation

J Clin Oncol. 2002 Feb 15;20(4):957-65. doi: 10.1200/JCO.2002.20.4.957.


Purpose: To study safety, feasibility, and biologic activity of adenovirus-mediated p53 gene transfer in patients with bladder cancer.

Patients and methods: Twelve patients with histologically confirmed bladder cancer scheduled for cystectomy were treated on day 1 with a single intratumoral injection of SCH 58500 (rAd/p53) at cystoscopy at one dose level (7.5 x 10(11) particles) or a single intravesical instillation of SCH 58500 with a transduction-enhancing agent (Big CHAP) at three dose levels (7.5 x 10(11) to 7.5 x 10(13) particles). Cystectomies were performed in 11 patients on day 3, and transgene expression, vector distribution, and biologic markers of transgene activity were assessed by molecular and immunohistochemical methods in tumors and normal bladder samples.

Results: Specific transgene expression was detected in tissues from seven of eight assessable patients treated with intravesical instillation of SCH 58500 but in none of three assessable patients treated with intratumoral injection of SCH 58500. Induction of RNA and protein expression of the p53 target gene p21/WAF1 was demonstrated in samples from patients treated with SCH 58500 instillation at higher dose levels. Distribution studies after intravesical instillation of SCH 58500 revealed both high transduction efficacy and vector penetration throughout the whole urothelium and into submucosal tumor cells. No dose-limiting toxicity was observed, and side effects were local and of transient nature.

Conclusion: Intravesical instillation of SCH 58500 combined with a transduction-enhancing agent is safe, feasible, and biologically active in patients with bladder cancer. Studies to evaluate the clinical efficacy of this treatment in patients with localized high-risk bladder cancer are warranted.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Administration, Intravesical
  • Adult
  • Aged
  • Aged, 80 and over
  • Cystectomy
  • DNA Primers
  • Dose-Response Relationship, Drug
  • Gene Transfer Techniques*
  • Genes, p53*
  • Genetic Therapy*
  • Genetic Vectors / therapeutic use*
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*


  • DNA Primers