A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas.
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.
Forsyth
Peter
P
Department of Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada. pforsyth@ucalgary.ca
Roldán
Gloria
G
George
David
D
Wallace
Carla
C
Palmer
Cheryl Ann
CA
Morris
Don
D
Cairncross
Gregory
G
Matthews
Maureen Vallee
MV
Markert
James
J
Gillespie
Yancey
Y
Coffey
Matt
M
Thompson
Brad
B
Hamilton
Mark
M
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
D000914:Antibodies, Viral