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

Svend O. Freytag, Hans Stricker, Mei Lu, Mohamed Elshaikh, Ibrahim Aref, Deepak Pradhan, Kenneth Levin, Jae Ho Kim, James Peabody, Farzan Siddiqui, Kenneth Barton, Jan Pegg, Yingshu Zhang, Jingfang Cheng, Nancy Oja-Tebbe, Renee Bourgeois, Nilesh Gupta, Zhaoli Lane, Ron Rodriguez, Theodore DeweeseBenjamin Movsas

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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.

Original languageEnglish (US)
Pages (from-to)268-276
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume89
Issue number2
DOIs
StatePublished - Jun 1 2014

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ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Freytag, S. O., Stricker, H., Lu, M., Elshaikh, M., Aref, I., Pradhan, D., Levin, K., Kim, J. H., Peabody, J., Siddiqui, F., Barton, K., Pegg, J., Zhang, Y., Cheng, J., Oja-Tebbe, N., Bourgeois, R., Gupta, N., Lane, Z., Rodriguez, R., ... Movsas, B. (2014). Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer. International Journal of Radiation Oncology Biology Physics, 89(2), 268-276. https://doi.org/10.1016/j.ijrobp.2014.02.034