Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1991-10-29
pubmed:abstractText
Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
5384-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:1913658-Adult, pubmed-meshheading:1913658-Animals, pubmed-meshheading:1913658-Antineoplastic Agents, pubmed-meshheading:1913658-Delayed-Action Preparations, pubmed-meshheading:1913658-Dogs, pubmed-meshheading:1913658-Dose-Response Relationship, Drug, pubmed-meshheading:1913658-Drug Implants, pubmed-meshheading:1913658-Fluorouracil, pubmed-meshheading:1913658-Head and Neck Neoplasms, pubmed-meshheading:1913658-Humans, pubmed-meshheading:1913658-Injections, Intravenous, pubmed-meshheading:1913658-Injections, Subcutaneous, pubmed-meshheading:1913658-Lactic Acid, pubmed-meshheading:1913658-Leukemia P388, pubmed-meshheading:1913658-Male, pubmed-meshheading:1913658-Mice, pubmed-meshheading:1913658-Middle Aged, pubmed-meshheading:1913658-Necrosis, pubmed-meshheading:1913658-Neoplasms, pubmed-meshheading:1913658-Polyglycolic Acid, pubmed-meshheading:1913658-Polymers, pubmed-meshheading:1913658-Rats, pubmed-meshheading:1913658-Rats, Inbred Strains, pubmed-meshheading:1913658-Skin, pubmed-meshheading:1913658-Vinblastine
pubmed:year
1991
pubmed:articleTitle
Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors.
pubmed:affiliation
Laboratoire de Pharmacodynamie Clinique, France.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Research Support, Non-U.S. Gov't