Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer.
OBJECTIVE
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
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.
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan. Electronic address: sfreyta1@hfhs.org.
Svend O
SO
Freytag
Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan.
Hans
H
Stricker
Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
Mei
M
Lu
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Mohamed
M
Elshaikh
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Ibrahim
I
Aref
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Deepak
D
Pradhan
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Kenneth
K
Levin
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Jae Ho
JH
Kim
Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan.
James
J
Peabody
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Farzan
F
Siddiqui
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Kenneth
K
Barton
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Jan
J
Pegg
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Yingshu
Y
Zhang
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Jingfang
J
Cheng
Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
Nancy
N
Oja-Tebbe
Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
Renee
R
Bourgeois
Pathology, Henry Ford Health System, Detroit, Michigan.
Nilesh
N
Gupta
Pathology, Henry Ford Health System, Detroit, Michigan.
Zhaoli
Z
Lane
Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ron
R
Rodriguez
Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Theodore
T
DeWeese
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan.
Benjamin
B
Movsas
D000256:Adenoviridae / Q000235:genetics*; D000368:Aged; D001706:Biopsy; D003131:Combined Modality Therapy / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D050130:Oncolytic Virotherapy / Q000379:methods; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D011788:Quality of Life; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome