Phase I, open-label, dose-escalating study of a genetically engineered herpes simplex virus, NV1020, in subjects with metastatic colorectal carcinoma to the liver - PubMed (original) (raw)
Clinical Trial
. 2006 Dec;17(12):1214-24.
doi: 10.1089/hum.2006.17.1214.
Karen Brown, Anne Covey, Teresa Kim, Amit Bhargava, Lynn Brody, Brenda Guilfoyle, Natasha P Haag, Matthias Karrasch, Birgit Glasschroeder, Anette Knoll, George Getrajdman, K Jon Kowal, William R Jarnagin, Yuman Fong
Affiliations
- PMID: 17107303
- DOI: 10.1089/hum.2006.17.1214
Clinical Trial
Phase I, open-label, dose-escalating study of a genetically engineered herpes simplex virus, NV1020, in subjects with metastatic colorectal carcinoma to the liver
Nancy Kemeny et al. Hum Gene Ther. 2006 Dec.
Abstract
Current regimens of systemic chemotherapy result in only modest lengthening of survival in patients with advanced stage, liver-dominant, metastatic colorectal cancer who have failed first-line chemotherapy. The objective of this study was to investigate the safety and tolerability of NV1020, a replication-competent, attenuated, genetically engineered herpes simplex virus type 1 (HSV-1), in patients with hepatic colorectal metastases refractory to first-line chemotherapy. A phase I, open-label, dose-escalating study of a single 10-min hepatic arterial infusion of NV1020 in four cohorts. Three patients in each cohort received doses of 3 x 10(6), 1 x 10(7), 3 x 10(7), and 1 x 10(8) plaque-forming units. Adverse events were either mild or moderate in severity, and self-limiting. Only three serious adverse events (one transient rise in serum y-glutamyltransferase, one diarrhea, and one leukocytosis) experienced by three patients were considered to be possibly or probably related to NV1020. There were no deaths during the study, and there was no evidence of disseminated herpes infection. Viral presence was detected in only one saliva sample and two serum samples from one asymptomatic patient in the highest dose cohort. In the first week after viral administration only rare and minor increases were noted for tumor necrosis factor-alpha (six samples; three patients; peak, 40 pg/ml), interleukin (IL)-1 (two samples; two patients; peak, 28 pg/ml), and interferon-y (four samples; two subjects; peak, 54 pg/ml). No IL-2 was detected. Mild liver enzyme elevations were self-limiting and not associated with clinical symptoms. We conclude that NV1020, a genetically engineered but replication-competent HSV-1 oncolytic virus, can be safely administered into the hepatic artery without significant effects on normal liver function.
Similar articles
- Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver.
Geevarghese SK, Geller DA, de Haan HA, Hörer M, Knoll AE, Mescheder A, Nemunaitis J, Reid TR, Sze DY, Tanabe KK, Tawfik H. Geevarghese SK, et al. Hum Gene Ther. 2010 Sep;21(9):1119-28. doi: 10.1089/hum.2010.020. Hum Gene Ther. 2010. PMID: 20486770 Free PMC article. Clinical Trial. - Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial.
Reid T, Galanis E, Abbruzzese J, Sze D, Andrews J, Romel L, Hatfield M, Rubin J, Kirn D. Reid T, et al. Gene Ther. 2001 Nov;8(21):1618-26. doi: 10.1038/sj.gt.3301512. Gene Ther. 2001. PMID: 11895000 Free PMC article. Clinical Trial. - Efficacy of oncolytic herpesvirus NV1020 can be enhanced by combination with chemotherapeutics in colon carcinoma cells.
Gutermann A, Mayer E, von Dehn-Rothfelser K, Breidenstein C, Weber M, Muench M, Gungor D, Suehnel J, Moebius U, Lechmann M. Gutermann A, et al. Hum Gene Ther. 2006 Dec;17(12):1241-53. doi: 10.1089/hum.2006.17.1241. Hum Gene Ther. 2006. PMID: 17117895 - Herpes simplex virus NV1020 as a novel and promising therapy for hepatic malignancy.
Kelly KJ, Wong J, Fong Y. Kelly KJ, et al. Expert Opin Investig Drugs. 2008 Jul;17(7):1105-13. doi: 10.1517/13543784.17.7.1105. Expert Opin Investig Drugs. 2008. PMID: 18549346 Free PMC article. Review. - Management of liver metastases from colorectal cancer.
Kemeny N. Kemeny N. Oncology (Williston Park). 2006 Sep;20(10):1161-76, 1179; discussion 1179-80, 1185-6. Oncology (Williston Park). 2006. PMID: 17024869 Review.
Cited by
- Development and application of oncolytic viruses as the nemesis of tumor cells.
Zhu X, Fan C, Xiong Z, Chen M, Li Z, Tao T, Liu X. Zhu X, et al. Front Microbiol. 2023 Jun 12;14:1188526. doi: 10.3389/fmicb.2023.1188526. eCollection 2023. Front Microbiol. 2023. PMID: 37440883 Free PMC article. Review. - HSV: The scout and assault for digestive system tumors.
Li S, Li Q, Ren Y, Yi J, Guo J, Kong X. Li S, et al. Front Mol Biosci. 2023 Feb 28;10:1142498. doi: 10.3389/fmolb.2023.1142498. eCollection 2023. Front Mol Biosci. 2023. PMID: 36926680 Free PMC article. Review. - The Dilemma of HSV-1 Oncolytic Virus Delivery: The Method Choice and Hurdles.
Tang G, Wang D, Zhao X, Feng Z, Chen Q, Shen Y. Tang G, et al. Int J Mol Sci. 2023 Feb 12;24(4):3681. doi: 10.3390/ijms24043681. Int J Mol Sci. 2023. PMID: 36835091 Free PMC article. Review. - Recombinant Oncolytic Adenovirus Combined with Cyclophosphamide Induces Synergy in the Treatment of Breast Cancer in vitro and in vivo.
Wang J, Zuo S, Zhang Y, Li S, Shi Y, Du T, Han J, Jin N, Li Y, Li X. Wang J, et al. Cancer Manag Res. 2022 Sep 15;14:2749-2761. doi: 10.2147/CMAR.S373271. eCollection 2022. Cancer Manag Res. 2022. PMID: 36133740 Free PMC article. - Herpes simplex virus 1 as an oncolytic viral therapy for refractory cancers.
Scanlan H, Coffman Z, Bettencourt J, Shipley T, Bramblett DE. Scanlan H, et al. Front Oncol. 2022 Jul 27;12:940019. doi: 10.3389/fonc.2022.940019. eCollection 2022. Front Oncol. 2022. PMID: 35965554 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical