title: A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer.
abstract: Genetically engineered herpes simplex viruses (HSVs) can selectively infect and replicate in cancer cells, and are candidates for use as oncolytic therapy. This long-term report of a phase I trial examines vascular administration of HSV as therapy for cancer. Twelve subjects with metastatic colorectal cancer within the liver failing first-line chemotherapy were treated in four cohorts with a single dose (3 x 10(6) to 1 x 10(8) particles) of NV1020, a multimutated, replication-competent HSV. After hepatic arterial administration, subjects were observed for 4 weeks before starting intra-arterial chemotherapy. All patients exhibited progression of disease before HSV injection. During observation, levels of the tumor marker carcinoembryonic antigen (CEA) decreased (median % drop = 24%; range 13-74%; P < 0.02). One of three individuals at the 10(8) level showed a 39% radiologic decrease in tumor size by cross-section and 75% by volume. HSV infection was documented from liver tumor biopsies. After beginning regional chemotherapy, all patients demonstrated a further decrease in CEA (median 96%; range 50-98%; P < 0.008) and a radiologic partial response. Median survival for this group was 25 months. During follow-up, no signs of virus reactivation were found. Multimutated HSV can be delivered safely into the human bloodstream to produce selective infection of tumor tissues and biologic effects.
authors.affiliation: 1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Teresa
authors.initials: T
authors.lastname: Kim
authors.forename: Amit
authors.initials: A
authors.lastname: Bhargava
authors.forename: Larry
authors.initials: L
authors.lastname: Schwartz
authors.forename: Karen
authors.initials: K
authors.lastname: Brown
authors.forename: Lynn
authors.initials: L
authors.lastname: Brody
authors.forename: Anne
authors.initials: A
authors.lastname: Covey
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.forename: George
authors.initials: G
authors.lastname: Getrajdman
authors.forename: Axel
authors.initials: A
authors.lastname: Mescheder
authors.forename: William
authors.initials: W
authors.lastname: Jarnagin
authors.forename: Nancy
authors.initials: N
authors.lastname: Kemeny
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D050130:Oncolytic Virotherapy / Q000379:methods*; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil