A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer Journal Article
| Authors: | Fong, Y.; Kim, T.; Bhargava, A.; Schwartz, L.; Brown, K.; Brody, L.; Covey, A.; Karrasch, M.; Getrajdman, G.; Mescheder, A.; Jarnagin, W.; Kemeny, N. |
| Article 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 × 10<sup>6</sup> to 1 × 10<sup>8</sup> 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<sup>8</sup> 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. |
| Keywords: | adult; cancer survival; clinical article; controlled study; human tissue; treatment outcome; aged; middle aged; genetics; clinical trial; drug tolerability; fluorouracil; cancer combination chemotherapy; cancer growth; dose response; drug safety; liver neoplasms; capecitabine; drug megadose; follow up; methodology; colorectal cancer; metastasis; controlled clinical trial; tumor volume; carcinoembryonic antigen; dexamethasone; antineoplastic activity; tumor regression; pathology; physiology; irinotecan; colorectal carcinoma; drug dose escalation; colorectal neoplasms; kaplan-meiers estimate; liver metastasis; colorectal tumor; folinic acid; liver tumor; simplexvirus; oncolytic virotherapy; single drug dose; phase 1 clinical trial; kaplan meier method; oxaliplatin; drug treatment failure; floxuridine; absence of side effects; nv 1020; herpes simplex virus; liver biopsy; herpes; leucovorin |
| Journal Title: | Molecular Therapy |
| Volume: | 17 |
| Issue: | 2 |
| ISSN: | 1525-0016 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-02-01 |
| Start Page: | 389 |
| End Page: | 394 |
| Language: | English |
| DOI: | 10.1038/mt.2008.240 |
| PUBMED: | 19018254 |
| PROVIDER: | scopus |
| PMCID: | PMC2835058 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: MTOHC" - "Source: Scopus" |
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