1. ¹Department of Neurosurgery, University of Kuopio, University of Kuopio, FIN-70211 Kuopio, Finland
2. ²Gene Therapy Unit, Kuopio University Hospital, FIN-70211 Kuopio, Finland
3. ³Department of Oncology, University of Kuopio, FIN-70211 Kuopio, Finland
4. ⁴Department of Radiology, University of Kuopio, FIN-70211 Kuopio, Finland
5. ⁵Ark Therapeutics Ltd, London, UK
6. ⁶Department of Molecular Medicine, University of Kuopio, FIN-70211 Kuopio, Finland
7. ⁷Department of Medicine, University of Kuopio, FIN-70211 Kuopio, Finland

Correspondence: Seppo Ylä-Herttuala, A.I.Virtanen Institute, University of Kuopio, P.O.Box 1627, FIN-70211 Kuopio, Finland. Fax: +358 17 163751 E-mail: seppo.ylaherttuala@uku.fi

^*These authors contributed eqaully to this article.

Received 30 April 2004; Accepted 5 August 2004.

Abstract

Malignant glioma is a devastating brain tumor with no effective treatment. This randomised, controlled study involved 36 patients with operable primary or recurrent malignant glioma. Seventeen patients were randomized to receive AdvHSV-tk gene therapy (3 10¹⁰ pfu) by local injection into the wound bed after tumor resection, followed by intravenous ganciclovir (GCV), 5 mg/kg twice daily for 14 days. The control group of 19 patients received standard care consisting of radical excision followed by radiotherapy in those patients with primary tumors. The primary end-point was survival as defined by death or surgery for recurrence. Secondary end-points were all-cause mortality and tumour progression as determined by MRI. Overall safety and quality of life were also assessed. Findings were also compared with historical controls (n = 36) from the same unit over 2 years preceding the study. AdvHSV-tk treatment produced a clinically and statistically significant increase in mean survival from 39.0 19.7 (SD) to 70.6 52.9 weeks (P = 0.0095, log-rank regression vs. randomized controls). The median survival time increased from 37.7 to 62.4 weeks. Six patients had increased anti-adenovirus antibody titers, without adverse effects. The treatment was well tolerated. It is concluded that AdvHSV-tk gene therapy with GCV is a potential new treatment for operable primary or recurrent high-grade glioma.