Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Non-Hybrid “(Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Identifieur interne : 001B45 ( Main/Exploration ); précédent : 001B44; suivant : 001B46Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Non-Hybrid “(Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Auteurs : Beata Holkova [États-Unis] ; Maciej Kmieciak [États-Unis] ; E. Brent Perkins [États-Unis] ; Prithviraj Bose [États-Unis] ; Rachid C. Baz [États-Unis] ; G. David Roodman [États-Unis] ; Robert K. Stuart [États-Unis] ; Viswanathan Ramakrishnan [États-Unis] ; Wen Wan [États-Unis] ; Cody J. Peer [États-Unis] ; Jana Dawson [États-Unis] ; Loveleen Kang [États-Unis] ; Connie Honeycutt [États-Unis] ; Mary Beth Tombes [États-Unis] ; Ellen Shrader [États-Unis] ; Caryn Weir-Wiggins [États-Unis] ; Martha Wellons [États-Unis] ; Heidi Sankala [États-Unis] ; Kevin T. Hogan [États-Unis] ; A. Dimitrios Colevas ; L. Austin Doyle ; William D. Figg [États-Unis] ; Domenico Coppola [États-Unis] ; John D. Roberts [États-Unis] ; Daniel Sullivan [États-Unis] ; Steven Grant [États-Unis]Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2014.
Descripteurs français
- KwdFr :
- Acides boroniques (administration et posologie), Acides boroniques (pharmacocinétique), Adulte, Adulte d'âge moyen, Association thérapeutique, Bortézomib, Calendrier d'administration des médicaments, Femelle, Flavonoïdes (administration et posologie), Flavonoïdes (pharmacocinétique), Humains, Lymphocytes B (anatomopathologie), Mâle, Pipéridines (administration et posologie), Pipéridines (pharmacocinétique), Protocoles de polychimiothérapie antinéoplasique (effets indésirables), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Pyrazines (administration et posologie), Pyrazines (pharmacocinétique), Reprise du traitement, Récidive, Résultat thérapeutique, Sujet âgé, Surveillance pharmacologique, Syndromes lymphoprolifératifs (anatomopathologie), Syndromes lymphoprolifératifs (diagnostic), Syndromes lymphoprolifératifs (traitement médicamenteux).
- MESH :
- administration et posologie : Acides boroniques, Flavonoïdes, Pipéridines, Pyrazines.
- anatomopathologie : Lymphocytes B, Syndromes lymphoprolifératifs.
- diagnostic : Syndromes lymphoprolifératifs.
- effets indésirables : Protocoles de polychimiothérapie antinéoplasique.
- pharmacocinétique : Acides boroniques, Flavonoïdes, Pipéridines, Pyrazines.
- traitement médicamenteux : Syndromes lymphoprolifératifs.
- usage thérapeutique : Protocoles de polychimiothérapie antinéoplasique.
- Adulte, Adulte d'âge moyen, Association thérapeutique, Bortézomib, Calendrier d'administration des médicaments, Femelle, Humains, Mâle, Reprise du traitement, Récidive, Résultat thérapeutique, Sujet âgé, Surveillance pharmacologique.
English descriptors
- KwdEn :
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols (adverse effects), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), B-Lymphocytes (pathology), Boronic Acids (administration & dosage), Boronic Acids (pharmacokinetics), Bortezomib, Combined Modality Therapy, Drug Administration Schedule, Drug Monitoring, Female, Flavonoids (administration & dosage), Flavonoids (pharmacokinetics), Humans, Lymphoproliferative Disorders (diagnosis), Lymphoproliferative Disorders (drug therapy), Lymphoproliferative Disorders (pathology), Male, Middle Aged, Piperidines (administration & dosage), Piperidines (pharmacokinetics), Pyrazines (administration & dosage), Pyrazines (pharmacokinetics), Recurrence, Retreatment, Treatment Outcome.
- MESH :
- chemical , administration & dosage : Boronic Acids, Flavonoids, Piperidines, Pyrazines.
- adverse effects : Antineoplastic Combined Chemotherapy Protocols.
- diagnosis : Lymphoproliferative Disorders.
- drug therapy : Lymphoproliferative Disorders.
- pathology : B-Lymphocytes, Lymphoproliferative Disorders.
- chemical , pharmacokinetics : Boronic Acids, Flavonoids, Piperidines, Pyrazines.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Adult, Aged, Bortezomib, Combined Modality Therapy, Drug Administration Schedule, Drug Monitoring, Female, Humans, Male, Middle Aged, Recurrence, Retreatment, Treatment Outcome.
Abstract
This phase I study was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma [MM], indolent lymphoma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma).
Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted.
A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m2 for bortezomib and 40 mg/m2 for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common non-hematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses.
The combination of bortezomib and alvocidib is tolerable and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory MM or indolent non-Hodgkin's lymphoma. As the non-hybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies.
Url:
DOI: 10.1158/1078-0432.CCR-14-0805
PubMed: 25248382
PubMed Central: 4233160
Affiliations:
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Le document en format XML
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Lee Moffitt Cancer Center & Research Institute, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Internal Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">The Institute for Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>The Institute for Molecular Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25248382</idno><idno type="pmc">4233160</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233160</idno><idno type="RBID">PMC:4233160</idno><idno type="doi">10.1158/1078-0432.CCR-14-0805</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001914</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001914</idno><idno type="wicri:Area/Pmc/Curation">001889</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001889</idno><idno type="wicri:Area/Pmc/Checkpoint">000A01</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A01</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">001394</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001394</idno><idno type="wicri:Area/PubMed/Curation">001388</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001388</idno><idno type="wicri:Area/PubMed/Checkpoint">001388</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001388</idno><idno type="wicri:Area/Ncbi/Merge">003708</idno><idno type="wicri:Area/Ncbi/Curation">003708</idno><idno type="wicri:Area/Ncbi/Checkpoint">003708</idno><idno type="wicri:doubleKey">1078-0432:2014:Holkova B:phase:i:trial</idno><idno type="wicri:Area/Main/Merge">001C16</idno><idno type="wicri:Area/Main/Curation">001B45</idno><idno type="wicri:Area/Main/Exploration">001B45</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Non-Hybrid “(Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms</title><author><name sortKey="Holkova, Beata" sort="Holkova, Beata" uniqKey="Holkova B" first="Beata" last="Holkova">Beata Holkova</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Internal Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Kmieciak, Maciej" sort="Kmieciak, Maciej" uniqKey="Kmieciak M" first="Maciej" last="Kmieciak">Maciej Kmieciak</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Perkins, E Brent" sort="Perkins, E Brent" uniqKey="Perkins E" first="E. Brent" last="Perkins">E. Brent Perkins</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Internal Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Bose, Prithviraj" sort="Bose, Prithviraj" uniqKey="Bose P" first="Prithviraj" last="Bose">Prithviraj Bose</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Internal Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Baz, Rachid C" sort="Baz, Rachid C" uniqKey="Baz R" first="Rachid C." last="Baz">Rachid C. Baz</name><affiliation wicri:level="2"><nlm:aff id="A7">Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Roodman, G David" sort="Roodman, G David" uniqKey="Roodman G" first="G. David" last="Roodman">G. David Roodman</name><affiliation wicri:level="2"><nlm:aff id="A8">Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Medicine, University of Pittsburgh, Pittsburgh</wicri:cityArea></affiliation></author><author><name sortKey="Stuart, Robert K" sort="Stuart, Robert K" uniqKey="Stuart R" first="Robert K." last="Stuart">Robert K. Stuart</name><affiliation wicri:level="2"><nlm:aff id="A9">Department of Medicine, Medical University of South Carolina, Charleston, South Carolina</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>Department of Medicine, Medical University of South Carolina, Charleston</wicri:cityArea></affiliation></author><author><name sortKey="Ramakrishnan, Viswanathan" sort="Ramakrishnan, Viswanathan" uniqKey="Ramakrishnan V" first="Viswanathan" last="Ramakrishnan">Viswanathan Ramakrishnan</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biostatistics, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Wan, Wen" sort="Wan, Wen" uniqKey="Wan W" first="Wen" last="Wan">Wen Wan</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biostatistics, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Peer, Cody J" sort="Peer, Cody J" uniqKey="Peer C" first="Cody J" last="Peer">Cody J. Peer</name><affiliation wicri:level="2"><nlm:aff id="A10">Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Dawson, Jana" sort="Dawson, Jana" uniqKey="Dawson J" first="Jana" last="Dawson">Jana Dawson</name><affiliation wicri:level="2"><nlm:aff id="A7">Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Kang, Loveleen" sort="Kang, Loveleen" uniqKey="Kang L" first="Loveleen" last="Kang">Loveleen Kang</name><affiliation wicri:level="2"><nlm:aff id="A11">James A. Haley Veterans’ Hospital, Tampa, Florida</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>James A. Haley Veterans’ Hospital, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Honeycutt, Connie" sort="Honeycutt, Connie" uniqKey="Honeycutt C" first="Connie" last="Honeycutt">Connie Honeycutt</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Tombes, Mary Beth" sort="Tombes, Mary Beth" uniqKey="Tombes M" first="Mary Beth" last="Tombes">Mary Beth Tombes</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Shrader, Ellen" sort="Shrader, Ellen" uniqKey="Shrader E" first="Ellen" last="Shrader">Ellen Shrader</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Weir Wiggins, Caryn" sort="Weir Wiggins, Caryn" uniqKey="Weir Wiggins C" first="Caryn" last="Weir-Wiggins">Caryn Weir-Wiggins</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Wellons, Martha" sort="Wellons, Martha" uniqKey="Wellons M" first="Martha" last="Wellons">Martha Wellons</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Sankala, Heidi" sort="Sankala, Heidi" uniqKey="Sankala H" first="Heidi" last="Sankala">Heidi Sankala</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Hogan, Kevin T" sort="Hogan, Kevin T" uniqKey="Hogan K" first="Kevin T." last="Hogan">Kevin T. Hogan</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Colevas, A Dimitrios" sort="Colevas, A Dimitrios" uniqKey="Colevas A" first="A. Dimitrios" last="Colevas">A. Dimitrios Colevas</name><affiliation><nlm:aff id="A12">Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.</nlm:aff><wicri:noCountry code="subfield">Maryland.</wicri:noCountry></affiliation></author><author><name sortKey="Doyle, L Austin" sort="Doyle, L Austin" uniqKey="Doyle L" first="L. Austin" last="Doyle">L. Austin Doyle</name><affiliation><nlm:aff id="A12">Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.</nlm:aff><wicri:noCountry code="subfield">Maryland.</wicri:noCountry></affiliation></author><author><name sortKey="Figg, William D" sort="Figg, William D" uniqKey="Figg W" first="William D." last="Figg">William D. Figg</name><affiliation wicri:level="2"><nlm:aff id="A10">Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Coppola, Domenico" sort="Coppola, Domenico" uniqKey="Coppola D" first="Domenico" last="Coppola">Domenico Coppola</name><affiliation wicri:level="2"><nlm:aff id="A7">Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Roberts, John D" sort="Roberts, John D" uniqKey="Roberts J" first="John D." last="Roberts">John D. Roberts</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Internal Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Sullivan, Daniel" sort="Sullivan, Daniel" uniqKey="Sullivan D" first="Daniel" last="Sullivan">Daniel Sullivan</name><affiliation wicri:level="2"><nlm:aff id="A7">Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><affiliation wicri:level="2"><nlm:aff id="A1">Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Massey Cancer Center, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Internal Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A4">Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A6">The Institute for Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>The Institute for Molecular Medicine, Virginia Commonwealth University, Richmond</wicri:cityArea></affiliation></author></analytic><series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title><idno type="ISSN">1078-0432</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Antineoplastic Combined Chemotherapy Protocols (adverse effects)</term><term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term><term>B-Lymphocytes (pathology)</term><term>Boronic Acids (administration & dosage)</term><term>Boronic Acids (pharmacokinetics)</term><term>Bortezomib</term><term>Combined Modality Therapy</term><term>Drug Administration Schedule</term><term>Drug Monitoring</term><term>Female</term><term>Flavonoids (administration & dosage)</term><term>Flavonoids (pharmacokinetics)</term><term>Humans</term><term>Lymphoproliferative Disorders (diagnosis)</term><term>Lymphoproliferative Disorders (drug therapy)</term><term>Lymphoproliferative Disorders (pathology)</term><term>Male</term><term>Middle Aged</term><term>Piperidines (administration & dosage)</term><term>Piperidines (pharmacokinetics)</term><term>Pyrazines (administration & dosage)</term><term>Pyrazines (pharmacokinetics)</term><term>Recurrence</term><term>Retreatment</term><term>Treatment Outcome</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides boroniques (administration et posologie)</term><term>Acides boroniques (pharmacocinétique)</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Association thérapeutique</term><term>Bortézomib</term><term>Calendrier d'administration des médicaments</term><term>Femelle</term><term>Flavonoïdes (administration et posologie)</term><term>Flavonoïdes (pharmacocinétique)</term><term>Humains</term><term>Lymphocytes B (anatomopathologie)</term><term>Mâle</term><term>Pipéridines (administration et posologie)</term><term>Pipéridines (pharmacocinétique)</term><term>Protocoles de polychimiothérapie antinéoplasique (effets indésirables)</term><term>Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique)</term><term>Pyrazines (administration et posologie)</term><term>Pyrazines (pharmacocinétique)</term><term>Reprise du traitement</term><term>Récidive</term><term>Résultat thérapeutique</term><term>Sujet âgé</term><term>Surveillance pharmacologique</term><term>Syndromes lymphoprolifératifs (anatomopathologie)</term><term>Syndromes lymphoprolifératifs (diagnostic)</term><term>Syndromes lymphoprolifératifs (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Boronic Acids</term><term>Flavonoids</term><term>Piperidines</term><term>Pyrazines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Acides boroniques</term><term>Flavonoïdes</term><term>Pipéridines</term><term>Pyrazines</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphocytes B</term><term>Syndromes lymphoprolifératifs</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Syndromes lymphoprolifératifs</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Protocoles de polychimiothérapie antinéoplasique</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>B-Lymphocytes</term><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Acides boroniques</term><term>Flavonoïdes</term><term>Pipéridines</term><term>Pyrazines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Boronic Acids</term><term>Flavonoids</term><term>Piperidines</term><term>Pyrazines</term></keywords><keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Syndromes lymphoprolifératifs</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Protocoles de polychimiothérapie antinéoplasique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Bortezomib</term><term>Combined Modality Therapy</term><term>Drug Administration Schedule</term><term>Drug Monitoring</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Recurrence</term><term>Retreatment</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Association thérapeutique</term><term>Bortézomib</term><term>Calendrier d'administration des médicaments</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Reprise du traitement</term><term>Récidive</term><term>Résultat thérapeutique</term><term>Sujet âgé</term><term>Surveillance pharmacologique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title><p id="P3">This phase I study was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma [MM], indolent lymphoma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma).</p></sec><sec id="S2"><title>Experimental Design</title><p id="P4">Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted.</p></sec><sec id="S3"><title>Results</title><p id="P5">A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m<sup>2</sup> for bortezomib and 40 mg/m<sup>2</sup> for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common non-hematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses.</p></sec><sec id="S4"><title>Conclusions</title><p id="P6">The combination of bortezomib and alvocidib is tolerable and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory MM or indolent non-Hodgkin's lymphoma. As the non-hybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies.</p></sec></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Sud</li><li>Floride</li><li>Maryland</li><li>Pennsylvanie</li><li>Virginie</li></region></list><tree><noCountry><name sortKey="Colevas, A Dimitrios" sort="Colevas, A Dimitrios" uniqKey="Colevas A" first="A. Dimitrios" last="Colevas">A. Dimitrios Colevas</name><name sortKey="Doyle, L Austin" sort="Doyle, L Austin" uniqKey="Doyle L" first="L. Austin" last="Doyle">L. Austin Doyle</name></noCountry><country name="États-Unis"><region name="Virginie"><name sortKey="Holkova, Beata" sort="Holkova, Beata" uniqKey="Holkova B" first="Beata" last="Holkova">Beata Holkova</name></region><name sortKey="Baz, Rachid C" sort="Baz, Rachid C" uniqKey="Baz R" first="Rachid C." last="Baz">Rachid C. Baz</name><name sortKey="Bose, Prithviraj" sort="Bose, Prithviraj" uniqKey="Bose P" first="Prithviraj" last="Bose">Prithviraj Bose</name><name sortKey="Bose, Prithviraj" sort="Bose, Prithviraj" uniqKey="Bose P" first="Prithviraj" last="Bose">Prithviraj Bose</name><name sortKey="Coppola, Domenico" sort="Coppola, Domenico" uniqKey="Coppola D" first="Domenico" last="Coppola">Domenico Coppola</name><name sortKey="Dawson, Jana" sort="Dawson, Jana" uniqKey="Dawson J" first="Jana" last="Dawson">Jana Dawson</name><name sortKey="Figg, William D" sort="Figg, William D" uniqKey="Figg W" first="William D." last="Figg">William D. Figg</name><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><name sortKey="Hogan, Kevin T" sort="Hogan, Kevin T" uniqKey="Hogan K" first="Kevin T." last="Hogan">Kevin T. Hogan</name><name sortKey="Holkova, Beata" sort="Holkova, Beata" uniqKey="Holkova B" first="Beata" last="Holkova">Beata Holkova</name><name sortKey="Honeycutt, Connie" sort="Honeycutt, Connie" uniqKey="Honeycutt C" first="Connie" last="Honeycutt">Connie Honeycutt</name><name sortKey="Kang, Loveleen" sort="Kang, Loveleen" uniqKey="Kang L" first="Loveleen" last="Kang">Loveleen Kang</name><name sortKey="Kmieciak, Maciej" sort="Kmieciak, Maciej" uniqKey="Kmieciak M" first="Maciej" last="Kmieciak">Maciej Kmieciak</name><name sortKey="Peer, Cody J" sort="Peer, Cody J" uniqKey="Peer C" first="Cody J" last="Peer">Cody J. Peer</name><name sortKey="Perkins, E Brent" sort="Perkins, E Brent" uniqKey="Perkins E" first="E. Brent" last="Perkins">E. Brent Perkins</name><name sortKey="Perkins, E Brent" sort="Perkins, E Brent" uniqKey="Perkins E" first="E. Brent" last="Perkins">E. Brent Perkins</name><name sortKey="Ramakrishnan, Viswanathan" sort="Ramakrishnan, Viswanathan" uniqKey="Ramakrishnan V" first="Viswanathan" last="Ramakrishnan">Viswanathan Ramakrishnan</name><name sortKey="Roberts, John D" sort="Roberts, John D" uniqKey="Roberts J" first="John D." last="Roberts">John D. Roberts</name><name sortKey="Roberts, John D" sort="Roberts, John D" uniqKey="Roberts J" first="John D." last="Roberts">John D. Roberts</name><name sortKey="Roodman, G David" sort="Roodman, G David" uniqKey="Roodman G" first="G. David" last="Roodman">G. David Roodman</name><name sortKey="Sankala, Heidi" sort="Sankala, Heidi" uniqKey="Sankala H" first="Heidi" last="Sankala">Heidi Sankala</name><name sortKey="Shrader, Ellen" sort="Shrader, Ellen" uniqKey="Shrader E" first="Ellen" last="Shrader">Ellen Shrader</name><name sortKey="Stuart, Robert K" sort="Stuart, Robert K" uniqKey="Stuart R" first="Robert K." last="Stuart">Robert K. Stuart</name><name sortKey="Sullivan, Daniel" sort="Sullivan, Daniel" uniqKey="Sullivan D" first="Daniel" last="Sullivan">Daniel Sullivan</name><name sortKey="Tombes, Mary Beth" sort="Tombes, Mary Beth" uniqKey="Tombes M" first="Mary Beth" last="Tombes">Mary Beth Tombes</name><name sortKey="Wan, Wen" sort="Wan, Wen" uniqKey="Wan W" first="Wen" last="Wan">Wen Wan</name><name sortKey="Weir Wiggins, Caryn" sort="Weir Wiggins, Caryn" uniqKey="Weir Wiggins C" first="Caryn" last="Weir-Wiggins">Caryn Weir-Wiggins</name><name sortKey="Wellons, Martha" sort="Wellons, Martha" uniqKey="Wellons M" first="Martha" last="Wellons">Martha Wellons</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Amérique/explor/PittsburghV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001B45 | SxmlIndent | more
Ou
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|texte= Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Non-Hybrid “(Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
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| NlmPubMed2Wicri -a PittsburghV1
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