title: Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma.
abstract: Reovirus, a replication competent RNA virus, has preclinical activity against melanoma lines and xenografts. We conducted a phase II trial of reovirus in metastatic melanoma patients. Patients received 3 × 10(10) TCID50 on days 1-5 of each 28 day cycle, administered intravenously. Twenty-one eligible patients were enrolled. Treatment was well tolerated without any dose reductions having to be implemented. Post-treatment biopsy samples were obtained in 15 patients, 13/15 contained adequate tumor for correlative analysis. In two patients, productive reoviral replication (viral antigen coexpression with tubulin) was demonstrated, despite increase in neutralizing antibody titers. There were no objective responses although 75-90% tumor necrosis, consistent with treatment effect, was observed in one patient who had metastatic lesions surgically removed. Median time to progression and survival were 45 days (range 13-96 days) and 165 days (range 15 days-15.8 months) respectively. In conclusion, reovirus treatment was well tolerated in metastatic melanoma patients; viral replication was demonstrated in biopsy samples. Based on preclinical data showing synergy with taxane and platinum compounds, a phase II combination trial in metastatic melanoma patients is ongoing.
authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA. galanis.evanthia@mayo.edu
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Richard G
authors.initials: RG
authors.lastname: Vile
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kottke
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Nevala
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thompson
authors.forename: Jean E
authors.initials: JE
authors.lastname: Lewis
authors.forename: Kandelaria M
authors.initials: KM
authors.lastname: Rumilla
authors.forename: Victoria
authors.initials: V
authors.lastname: Roulstone
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Linette
authors.forename: William J
authors.initials: WJ
authors.lastname: Maples
authors.forename: Matt
authors.initials: M
authors.lastname: Coffey
authors.forename: James
authors.initials: J
authors.lastname: Zwiebel
authors.forename: Kari
authors.initials: K
authors.lastname: Kendra
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D012089:Mammalian orthoreovirus 3 / Q000502:physiology; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D050130:Oncolytic Virotherapy / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D014779:Virus Replication; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins