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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2004-5-26
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pubmed:abstractText |
Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented antitumor activity in multiple myeloma and other lymphoid malignancies. We performed a Phase I study to investigate the maximum tolerated dose and dose-limiting toxicity of bortezomib in patients with acute leukemias refractory to or relapsing after prior therapy. Fifteen patients were treated with 0.75 (n = 3), 1.25 (n = 7), or 1.5 (n = 5) mg/m(2) bortezomib administered twice weekly for 4 weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n = 2), nausea (n = 2), diarrhea (n = 1), and fluid retention (n = 1), all at 1.5 mg/m(2) bortezomib. Proteasome inhibition was dose dependent and reached 68% at 1.5 mg/m(2) bortezomib. Peak inhibition was observed 1 h after treatment and returned to near baseline levels by 72 h after treatment. Incubation of blast cells with bortezomib in vitro showed induction of apoptosis in three of five patients investigated. We conclude that the maximum tolerated dose of bortezomib in patients with acute leukemia is 1.25 mg/m(2), using a twice-weekly for 4 weeks every 6 weeks schedule. The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1078-0432
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pubmed:author |
pubmed-author:CortesJorgeJ,
pubmed-author:EsteyElihuE,
pubmed-author:FaderlStefanS,
pubmed-author:Garcia-ManeroGuillermoG,
pubmed-author:GilesFrancisF,
pubmed-author:GuercioliniRobertoR,
pubmed-author:KantarjianHagopH,
pubmed-author:KollerCharlesC,
pubmed-author:McConkeyDavidD,
pubmed-author:PatelGiraG,
pubmed-author:RuizStacey LSL,
pubmed-author:ThomasDeborahD,
pubmed-author:WrightJohnJ
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
10
|
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
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pubmed:pagination |
3371-6
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15161691-Adolescent,
pubmed-meshheading:15161691-Adult,
pubmed-meshheading:15161691-Aged,
pubmed-meshheading:15161691-Antineoplastic Agents,
pubmed-meshheading:15161691-Apoptosis,
pubmed-meshheading:15161691-Boronic Acids,
pubmed-meshheading:15161691-Dose-Response Relationship, Drug,
pubmed-meshheading:15161691-Humans,
pubmed-meshheading:15161691-Leukemia, Myeloid, Acute,
pubmed-meshheading:15161691-Maximum Tolerated Dose,
pubmed-meshheading:15161691-Middle Aged,
pubmed-meshheading:15161691-Models, Chemical,
pubmed-meshheading:15161691-Myelodysplastic Syndromes,
pubmed-meshheading:15161691-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:15161691-Proteasome Endopeptidase Complex,
pubmed-meshheading:15161691-Pyrazines,
pubmed-meshheading:15161691-Recurrence,
pubmed-meshheading:15161691-Time Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Phase I study of bortezomib in refractory or relapsed acute leukemias.
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pubmed:affiliation |
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jcortes@mdanderson.org
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Clinical Trial, Phase I
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