title: A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas.
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 > or = 60, received prior radiotherapy with or without chemotherapy, and had up to the third recurrence of MG. Reovirus was administered intratumorally stereotactically at 1 x 10(7), 1 x 10(8), or 1 x 10(9) 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.
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada. pforsyth@ucalgary.ca
authors.forename: Peter
authors.initials: P
authors.lastname: Forsyth
authors.forename: Gloria
authors.initials: G
authors.lastname: Roldán
authors.forename: David
authors.initials: D
authors.lastname: George
authors.forename: Carla
authors.initials: C
authors.lastname: Wallace
authors.forename: Cheryl Ann
authors.initials: CA
authors.lastname: Palmer
authors.forename: Don
authors.initials: D
authors.lastname: Morris
authors.forename: Gregory
authors.initials: G
authors.lastname: Cairncross
authors.forename: Maureen Vallee
authors.initials: MV
authors.lastname: Matthews
authors.forename: James
authors.initials: J
authors.lastname: Markert
authors.forename: Yancey
authors.initials: Y
authors.lastname: Gillespie
authors.forename: Matt
authors.initials: M
authors.lastname: Coffey
authors.forename: Brad
authors.initials: B
authors.lastname: Thompson
authors.forename: Mark
authors.initials: M
authors.lastname: Hamilton
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006261:Headache / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology; D009364:Neoplasm Recurrence, Local; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D050504:Oncolytic Viruses / Q000276:immunology / Q000502:physiology; D012087:Reoviridae / Q000276:immunology / Q000502:physiology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000914:Antibodies, Viral