Linked Life Data

14612551

Source:http://linkedlifedata.com/resource/pubmed/id/14612551

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2003-11-12
pubmed:abstractText
The primary study objective was to determine the safety of intraprostatic administration of a replication-competent, oncolytic adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene concomitant with increasing durations of 5-fluorocytosine and valganciclovir prodrug therapy and conventional-dose three-dimensional conformal radiation therapy (3D-CRT) in patients with newly diagnosed, intermediate- to high-risk prostate cancer. Secondary objectives were to determine the persistence of therapeutic transgene expression in the prostate and to examine early posttreatment response. Fifteen patients in five cohorts received a single intraprostatic injection of 10(12) viral particles of the replication-competent Ad5-CD/TKrep adenovirus on day 1. Two days later, patients were administered 5-fluorocytosine and valganciclovir prodrug therapy for 1 (cohorts 1-3), 2 (cohort 4), or 3 (cohort 5) weeks along with 70-74 Gy 3D-CRT. Sextant needle biopsy of the prostate was obtained at 2 (cohort 1), 3 (cohort 2), and 4 (cohort 3) weeks for determination of the persistence of transgene expression. There were no dose-limiting toxicities and no significant treatment-related adverse events. Ninety-four percent of the adverse events observed were mild to moderate and self-limiting. Acute urinary and gastrointestinal toxicities were similar to those expected for conventional-dose 3D-CRT. Therapeutic transgene expression was found to persist in the prostate for up to 3 weeks after the adenovirus injection. As expected for patients receiving definitive radiation therapy, all patients experienced significant declines in prostate-specific antigen (PSA). The mean PSA half-life in patients administered more than 1 week of prodrug therapy was significantly shorter than that of patients receiving prodrugs for only 1 week (0.6 versus 2.0 months; P < 0.02) and markedly shorter than that reported previously for patients treated with conventional-dose 3D-CRT alone (2.4 months). With a median follow-up of only 9 months, 5 of 10 (50%) patients not treated with androgen-deprivation therapy achieved a serum PSA < or = 0.5 ng/ml. The results demonstrate that replication-competent adenovirus-mediated double-suicide gene therapy can be combined safely with conventional-dose 3D-CRT in patients with intermediate- to high-risk prostate cancer. The shorter than expected PSA half-life in patients receiving more than 1 week of prodrug therapy may suggest a possible interaction between the oncolytic adenovirus and/or double-suicide gene therapies and radiation therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7497-506
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14612551-Adenoviruses, Human, pubmed-meshheading:14612551-Aged, pubmed-meshheading:14612551-Aged, 80 and over, pubmed-meshheading:14612551-Combined Modality Therapy, pubmed-meshheading:14612551-Cytosine Deaminase, pubmed-meshheading:14612551-DNA, Viral, pubmed-meshheading:14612551-Flucytosine, pubmed-meshheading:14612551-Ganciclovir, pubmed-meshheading:14612551-Gene Expression, pubmed-meshheading:14612551-Gene Therapy, pubmed-meshheading:14612551-Humans, pubmed-meshheading:14612551-Male, pubmed-meshheading:14612551-Middle Aged, pubmed-meshheading:14612551-Prostatic Neoplasms, pubmed-meshheading:14612551-Recombinant Fusion Proteins, pubmed-meshheading:14612551-Simplexvirus, pubmed-meshheading:14612551-Thymidine Kinase, pubmed-meshheading:14612551-Transgenes, pubmed-meshheading:14612551-Virus Replication
pubmed:year
2003
pubmed:articleTitle
Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer.
pubmed:affiliation
Department of Radiation Oncology, Henry Ford Health System, One Ford Place, Detroit, Michigan 48202, USA. sfreyta1@hfhs.org
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Clinical Trial, Phase I