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

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.

Conflict of interest statement

Conflict of interest: none.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Fig. 1

EPIC scores. Mean ± 95% confidence interval values are plotted for each arm. Domain scores at 6, 12, 24, and 36 months were normalized to the patient’s own baseline value (defined as 100%) before the mean for each arm was determined. Mean raw scores for each domain at baseline are shown in Table 1. *Indicates significant differences between the arms, and the P value is shown. EPIC = Expanded Prostate Cancer Index Composite.

Fig. 2

EQ-5D scores. Mean ± 95% confidence interval values are plotted for each arm. Domain scores at 6, 12, 24, and 36 months were normalized to the patient’s own baseline value (defined as 100%) before the mean for each arm was determined. Mean raw scores for each domain at baseline are shown in Table 1. *Indicates significant differences between the arms, and the P value is shown. EQ-5D = quality of life health status instrument.