Source:http://linkedlifedata.com/resource/pubmed/id/15486072
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-1-20
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pubmed:abstractText |
Clofarabine (2-chloro-2'-fluoro-deoxy-9-beta-D-arabinofuranosyladenine) is a second-generation nucleoside analog with activity in acute leukemias. As clofarabine is a potent inhibitor of ribonucleotide reductase (RnR), we hypothesized that clofarabine will modulate ara-c triphosphate accumulation and increase the antileukemic activity of cytarabine (ara-C). We conducted a phase 1-2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25 acute myeloid leukemia [AML], 2 acute lymphoblastic leukemia [ALL]), 4 high-risk myelodysplastic syndrome (MDS), and 1 blast-phase chronic myeloid leukemia (CML).(1) Clofarabine was given as a 1-hour intravenous infusion for 5 days (days 2 through 6) followed 4 hours later by ara-C at 1 g/m(2) per day as a 2-hour intravenous infusion for 5 days (days 1 through 5). The phase 2 dose of clofarabine was 40 mg/m(2) per day for 5 days. Among all patients, 7 (22%) achieved complete remission (CR), and 5 (16%) achieved CR with incomplete platelet recovery (CRp), for an overall response rate of 38%. No responses occurred in 3 patients with ALL and CML. One patient (3%) died during induction. Adverse events were mainly less than or equal to grade 2, including transient liver test abnormalities, nausea/vomiting, diarrhea, skin rashes, mucositis, and palmoplantar erythrodysesthesias. Plasma clofarabine levels generated clofarabine triphosphate accumulation, which resulted in an increase in ara-CTP in the leukemic blasts. The combination of clofarabine with ara-C is safe and active. Cellular pharmacology data support the biochemical modulation strategy.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:BeranMiloslavM,
pubmed-author:BonatePeterP,
pubmed-author:CortesJorgeJ,
pubmed-author:DuMinM,
pubmed-author:EsteyElihuE,
pubmed-author:EstrovZeevZ,
pubmed-author:FaderlStefanS,
pubmed-author:FerrajoliAlessandraA,
pubmed-author:GandhiVarshaV,
pubmed-author:Garcia-ManeroGuillermoG,
pubmed-author:GilesFrancis JFJ,
pubmed-author:KantarjianHagopH,
pubmed-author:KeatingMichaelM,
pubmed-author:KwariMonicaM,
pubmed-author:O'BrienSusanS,
pubmed-author:PlunkettWilliamW,
pubmed-author:WierdaWilliamW
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
940-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15486072-Acute Disease,
pubmed-meshheading:15486072-Adenine Nucleotides,
pubmed-meshheading:15486072-Aged,
pubmed-meshheading:15486072-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:15486072-Arabinonucleosides,
pubmed-meshheading:15486072-Cytarabine,
pubmed-meshheading:15486072-Drug Administration Schedule,
pubmed-meshheading:15486072-Female,
pubmed-meshheading:15486072-Humans,
pubmed-meshheading:15486072-Infusions, Intravenous,
pubmed-meshheading:15486072-Karyotyping,
pubmed-meshheading:15486072-Leukemia,
pubmed-meshheading:15486072-Male,
pubmed-meshheading:15486072-Middle Aged,
pubmed-meshheading:15486072-Recurrence,
pubmed-meshheading:15486072-Treatment Outcome
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pubmed:year |
2005
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pubmed:articleTitle |
Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias.
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pubmed:affiliation |
Department of Leukemia, Box 428, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. sfaderl@mdanderson.org
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Clinical Trial, Phase II,
Clinical Trial, Phase I
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