Linked Life Data

18278438

Source:http://linkedlifedata.com/resource/pubmed/id/18278438

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-6-20
pubmed:abstractText
3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m(2) intravenously days 1-4 and 15-18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8-58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0167-6997
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
369-79
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:18278438-Adenocarcinoma, pubmed-meshheading:18278438-Aged, pubmed-meshheading:18278438-Antineoplastic Agents, pubmed-meshheading:18278438-Deoxycytidine, pubmed-meshheading:18278438-Disease Progression, pubmed-meshheading:18278438-Female, pubmed-meshheading:18278438-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18278438-Genes, MDR, pubmed-meshheading:18278438-Humans, pubmed-meshheading:18278438-Leukopenia, pubmed-meshheading:18278438-Male, pubmed-meshheading:18278438-Middle Aged, pubmed-meshheading:18278438-Mouth Mucosa, pubmed-meshheading:18278438-Pancreatic Neoplasms, pubmed-meshheading:18278438-Polymorphism, Genetic, pubmed-meshheading:18278438-Pyridines, pubmed-meshheading:18278438-Ribonucleoside Diphosphate Reductase, pubmed-meshheading:18278438-Survival Rate, pubmed-meshheading:18278438-Thiosemicarbazones, pubmed-meshheading:18278438-Treatment Outcome
pubmed:year
2008
pubmed:articleTitle
A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas.
pubmed:affiliation
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, 600 Highland Avenue, K4/528, Madison, WI 53792, USA.
pubmed:publicationType
Journal Article, Multicenter Study, Clinical Trial, Phase II, Research Support, N.I.H., Extramural