Document Detail


A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer.
MedLine Citation:
PMID:  16690359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CG7870 is a replication-selective oncolytic adenovirus genetically engineered to replicate preferentially in prostate tissue. In a previous phase I/II clinical trial of intraprostatic delivery of CG7870 for locally recurrent prostate cancer this virus was well tolerated. In this phase I study CG7870 was administered as a single intravenous infusion in a group-sequential dose escalation design (1 x 10(10) to 6 x 10(12) viral particles (vp)) to 23 patients with hormone-refractory metastatic prostate cancer. Flulike symptoms (fever, fatigue, rigors, nausea, and/or vomiting) were the most common adverse events. Three therapy-related grade 3 adverse events were reported, one of which (fatigue) was serious. At doses greater than 10(12) vp all five patients experienced asymptomatic grade 1 to 2 transaminitis and/or isolated d-dimer elevations starting on day 2 through 8; dose escalation was therefore halted at 6 x 10(12) vp. All tested patients had CG7870 genomes present in the peripheral blood for at least 90 minutes after infusion; patients in the highest dose group had persistence of genomes through 29 days. A "secondary" or "delayed" peak in plasma CG7870 genome copies (defined as a >10-fold increase in CG7870 genomes from nadir concentration) suggestive of active viral replication and shedding into the bloodstream was detected in 16/23 (70%) patients. CG7870 was detected in the saliva of 3 patients, whereas all urine samples tested negative. All patients developed antibodies to CG7870. Dose-related increases in interleukins 6 and 10 (IL-6, IL-10) blood levels were detected. The peak IL-6 concentration after CG7870 treatment was associated with a transient, asymptomatic decrease in blood pressure. No partial or complete prostate-specific antigen (PSA) responses were observed; however, 5 patients had a decrease in serum PSA of 25% to 49% following a single treatment, including 3 of 8 patients at the highest dose levels.
Authors:
Eric J Small; Michael A Carducci; James M Burke; Ron Rodriguez; Lawrence Fong; Lynn van Ummersen; D C Yu; Junko Aimi; Dale Ando; Peter Working; David Kirn; George Wilding
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-09
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  14     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-09-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  107-17     Citation Subset:  IM    
Affiliation:
University of California, Comprehensive Cancer Center San Francisco, San Francisco, CA 94143, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*,  immunology
Aged
Aged, 80 and over
Antibodies, Viral / blood
Blood Pressure / drug effects
Cytokines / blood
DNA Replication / genetics
Dose-Response Relationship, Drug
Gene Therapy / adverse effects,  methods*
Genetic Vectors / administration & dosage,  genetics,  pharmacokinetics
Humans
Infusions, Intravenous
Interleukin-10 / blood
Interleukin-6 / blood
Male
Middle Aged
Prostate-Specific Antigen / blood*
Prostatic Neoplasms / blood,  genetics,  therapy*
Saliva / metabolism
Tissue Distribution
Treatment Outcome
Grant Support
ID/Acronym/Agency:
CAP50-58236//PHS HHS
Chemical
Reg. No./Substance:
0/Antibodies, Viral; 0/Cytokines; 0/Interleukin-6; 130068-27-8/Interleukin-10; EC 3.4.21.77/Prostate-Specific Antigen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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