title: AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study.
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 x 10(10) 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.
authors.affiliation: Department of Neurosurgery, University of Kuopio, A.I. Virtanen Institute, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Immonen
authors.forename: Matti
authors.initials: M
authors.lastname: Vapalahti
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tyynelä
authors.forename: Heleena
authors.initials: H
authors.lastname: Hurskainen
authors.forename: Anu
authors.initials: A
authors.lastname: Sandmair
authors.forename: Ritva
authors.initials: R
authors.lastname: Vanninen
authors.forename: Gillian
authors.initials: G
authors.lastname: Langford
authors.forename: Neil
authors.initials: N
authors.lastname: Murray
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D013937:Thymidine Kinase; D015774:Ganciclovir