1. ¹Department of Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada
2. ²Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
3. ³Clark Smith Integrated Brain Tumor Research Centre, Southern Alberta Cancer Research Institute, Calgary, Alberta, Canada
4. ⁴Department of Pathology, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
5. ⁵Department of Diagnostic Imaging, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
6. ⁶Department of Pathology, Division of Neuropathology, University of Alabama at Birmingham, Birmingham, Alabama, USA
7. ⁷Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
8. ⁸Oncolytics Biotech Inc., Calgary, Alberta, Canada
9. ⁹Department of Clinical Neurosciences, Division of Neurosurgery, Foothills Medical Centre, University of Calgary, Alberta, Canada

Correspondence: Peter Forsyth, Southern Alberta Cancer Research Institute, Health Research Innovation Centre 2AA19, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. E-mail: pforsyth@ucalgary.ca

Received 10 September 2007; Accepted 11 December 2007; Published online 5 February 2008.

Abstract

Reovirus is an oncolytic virus with activity in in vivo models of malignant gliomas (MGs). The primary aims were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of intratumoral administration of reovirus in patients with recurrent MGs. Response, survival, and time to progression (TTP) were secondary aims. Patients were adults, had Karnofsky Performance score 60, received prior radiotherapy with or without chemotherapy, and had up to the third recurrence of MG. Reovirus was administered intratumorally stereotactically at 1 10⁷, 1 10⁸, or 1 10⁹ tissue culture infectious dose 50 (TCID50) in a volume of 0.9 ml. Twelve patients were treated at three dose levels (3, 6, and 3 patients, respectively). Seven were men, median Karnofsky Performance score was 80, and median age was 53.5 years. There were no grade III or IV adverse events (AEs) definitely or probably related to treatment. Ten patients had tumor progression, one had stabilization, and one was not evaluable for response. Median survival was 21 weeks (range, 6–234), and one is alive 54 months after treatment. Median TTP was 4.3 weeks (range, 2.6–39). An MTD was not reached. The intratumoral administration of the genetically unmodified reovirus was well tolerated using these doses and schedule, in patients with recurrent MG.