A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer.
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.
Fong
Yuman
Y
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Kim
Teresa
T
Bhargava
Amit
A
Schwartz
Larry
L
Brown
Karen
K
Brody
Lynn
L
Covey
Anne
A
Karrasch
Matthias
M
Getrajdman
George
G
Mescheder
Axel
A
Jarnagin
William
W
Kemeny
Nancy
N
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
D002955:Leucovorin; D005472:Fluorouracil