Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer

Int J Radiat Oncol Biol Phys. 2014 Jun 1;89(2):268-76. doi: 10.1016/j.ijrobp.2014.02.034. Epub 2014 May 5.

Abstract

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer.

Methods and materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival.

Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer.

Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenoviridae / genetics*
  • Aged
  • Biopsy
  • Combined Modality Therapy / methods
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm, Residual
  • Oncolytic Virotherapy / methods
  • Prospective Studies
  • Prostate / pathology
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / therapy*
  • Quality of Life
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / methods*
  • Time Factors
  • Treatment Outcome