AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma:: A randomised, controlled study

Malignant glioma is a devastating brain tumour with no effective treatment. This randomised, controlled study involved 36 patients with operable primary or recurrent malignant glioma. Seventeen patients were randomised to receive AdvHSV-tk gene therapy (3 x 1010 pfu) by local injection into the wound bed after tumour 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 tumours. The primary endpoint 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 and GCV is a potential new treatment for operable primary or recurrent high-grade glioma.