Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms.
Identifieur interne : 001394 ( PubMed/Corpus ); précédent : 001393; suivant : 001395Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms.
Auteurs : Beata Holkova ; Maciej Kmieciak ; E Brent Perkins ; Prithviraj Bose ; Rachid C. Baz ; G David Roodman ; Robert K. Stuart ; Viswanathan Ramakrishnan ; Wen Wan ; Cody J. Peer ; Jana Dawson ; Loveleen Kang ; Connie Honeycutt ; Mary Beth Tombes ; Ellen Shrader ; Caryn Weir-Wiggins ; Martha Wellons ; Heidi Sankala ; Kevin T. Hogan ; A Dimitrios Colevas ; L Austin Doyle ; William D. Figg ; Domenico Coppola ; John D. Roberts ; Daniel Sullivan ; Steven GrantSource :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2014.
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 (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).
DOI: 10.1158/1078-0432.CCR-14-0805
PubMed: 25248382
Links to Exploration step
pubmed:25248382Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (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><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. bholkova@mcvh-vcu.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Kmieciak, Maciej" sort="Kmieciak, Maciej" uniqKey="Kmieciak M" first="Maciej" last="Kmieciak">Maciej Kmieciak</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Bose, Prithviraj" sort="Bose, Prithviraj" uniqKey="Bose P" first="Prithviraj" last="Bose">Prithviraj Bose</name><affiliation><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></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><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></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><nlm:affiliation>Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.</nlm:affiliation></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><nlm:affiliation>Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.</nlm:affiliation></affiliation></author><author><name sortKey="Ramakrishnan, Viswanathan" sort="Ramakrishnan, Viswanathan" uniqKey="Ramakrishnan V" first="Viswanathan" last="Ramakrishnan">Viswanathan Ramakrishnan</name><affiliation><nlm:affiliation>Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Wan, Wen" sort="Wan, Wen" uniqKey="Wan W" first="Wen" last="Wan">Wen Wan</name><affiliation><nlm:affiliation>Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></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><nlm:affiliation>Center for Cancer Research, NCI, NIH, Bethesda, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Dawson, Jana" sort="Dawson, Jana" uniqKey="Dawson J" first="Jana" last="Dawson">Jana Dawson</name><affiliation><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Kang, Loveleen" sort="Kang, Loveleen" uniqKey="Kang L" first="Loveleen" last="Kang">Loveleen Kang</name><affiliation><nlm:affiliation>James A. Haley Veterans' Hospital, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Honeycutt, Connie" sort="Honeycutt, Connie" uniqKey="Honeycutt C" first="Connie" last="Honeycutt">Connie Honeycutt</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></affiliation></author><author><name sortKey="Shrader, Ellen" sort="Shrader, Ellen" uniqKey="Shrader E" first="Ellen" last="Shrader">Ellen Shrader</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></affiliation></author><author><name sortKey="Wellons, Martha" sort="Wellons, Martha" uniqKey="Wellons M" first="Martha" last="Wellons">Martha Wellons</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></affiliation></author><author><name sortKey="Sankala, Heidi" sort="Sankala, Heidi" uniqKey="Sankala H" first="Heidi" last="Sankala">Heidi Sankala</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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:affiliation>Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of.</nlm:affiliation></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:affiliation>Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of.</nlm:affiliation></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><nlm:affiliation>Center for Cancer Research, NCI, NIH, Bethesda, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Coppola, Domenico" sort="Coppola, Domenico" uniqKey="Coppola D" first="Domenico" last="Coppola">Domenico Coppola</name><affiliation><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Sullivan, Daniel" sort="Sullivan, Daniel" uniqKey="Sullivan D" first="Daniel" last="Sullivan">Daniel Sullivan</name><affiliation><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><affiliation><nlm:affiliation>Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25248382</idno><idno type="pmid">25248382</idno><idno type="doi">10.1158/1078-0432.CCR-14-0805</idno><idno type="wicri:Area/PubMed/Corpus">001394</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001394</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (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><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. bholkova@mcvh-vcu.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Kmieciak, Maciej" sort="Kmieciak, Maciej" uniqKey="Kmieciak M" first="Maciej" last="Kmieciak">Maciej Kmieciak</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Bose, Prithviraj" sort="Bose, Prithviraj" uniqKey="Bose P" first="Prithviraj" last="Bose">Prithviraj Bose</name><affiliation><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></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><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></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><nlm:affiliation>Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.</nlm:affiliation></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><nlm:affiliation>Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.</nlm:affiliation></affiliation></author><author><name sortKey="Ramakrishnan, Viswanathan" sort="Ramakrishnan, Viswanathan" uniqKey="Ramakrishnan V" first="Viswanathan" last="Ramakrishnan">Viswanathan Ramakrishnan</name><affiliation><nlm:affiliation>Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Wan, Wen" sort="Wan, Wen" uniqKey="Wan W" first="Wen" last="Wan">Wen Wan</name><affiliation><nlm:affiliation>Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></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><nlm:affiliation>Center for Cancer Research, NCI, NIH, Bethesda, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Dawson, Jana" sort="Dawson, Jana" uniqKey="Dawson J" first="Jana" last="Dawson">Jana Dawson</name><affiliation><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Kang, Loveleen" sort="Kang, Loveleen" uniqKey="Kang L" first="Loveleen" last="Kang">Loveleen Kang</name><affiliation><nlm:affiliation>James A. Haley Veterans' Hospital, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Honeycutt, Connie" sort="Honeycutt, Connie" uniqKey="Honeycutt C" first="Connie" last="Honeycutt">Connie Honeycutt</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></affiliation></author><author><name sortKey="Shrader, Ellen" sort="Shrader, Ellen" uniqKey="Shrader E" first="Ellen" last="Shrader">Ellen Shrader</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></affiliation></author><author><name sortKey="Wellons, Martha" sort="Wellons, Martha" uniqKey="Wellons M" first="Martha" last="Wellons">Martha Wellons</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></affiliation></author><author><name sortKey="Sankala, Heidi" sort="Sankala, Heidi" uniqKey="Sankala H" first="Heidi" last="Sankala">Heidi Sankala</name><affiliation><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and.</nlm:affiliation></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:affiliation>Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of.</nlm:affiliation></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:affiliation>Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of.</nlm:affiliation></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><nlm:affiliation>Center for Cancer Research, NCI, NIH, Bethesda, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Coppola, Domenico" sort="Coppola, Domenico" uniqKey="Coppola D" first="Domenico" last="Coppola">Domenico Coppola</name><affiliation><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></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><nlm:affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Sullivan, Daniel" sort="Sullivan, Daniel" uniqKey="Sullivan D" first="Daniel" last="Sullivan">Daniel Sullivan</name><affiliation><nlm:affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</nlm:affiliation></affiliation></author><author><name sortKey="Grant, Steven" sort="Grant, Steven" uniqKey="Grant S" first="Steven" last="Grant">Steven Grant</name><affiliation><nlm:affiliation>Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and.</nlm:affiliation></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" type="published">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="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="adverse effects" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>B-Lymphocytes</term><term>Lymphoproliferative Disorders</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" 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></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25248382</PMID><DateCreated><Year>2014</Year><Month>11</Month><Day>15</Day></DateCreated><DateCompleted><Year>2015</Year><Month>07</Month><Day>09</Day></DateCompleted><DateRevised><Year>2017</Year><Month>08</Month><Day>01</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">1078-0432</ISSN><JournalIssue CitedMedium="Internet"><Volume>20</Volume><Issue>22</Issue><PubDate><Year>2014</Year><Month>Nov</Month><Day>15</Day></PubDate></JournalIssue><Title>Clinical cancer research : an official journal of the American Association for Cancer Research</Title><ISOAbbreviation>Clin. Cancer Res.</ISOAbbreviation></Journal><ArticleTitle>Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms.</ArticleTitle><Pagination><MedlinePgn>5652-62</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1158/1078-0432.CCR-14-0805</ELocationID><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).</AbstractText><AbstractText Label="EXPERIMENTAL DESIGN" NlmCategory="METHODS">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.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m(2) for bortezomib and 40 mg/m(2) for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic 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.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">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 multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies.</AbstractText><CopyrightInformation>©2014 American Association for Cancer Research.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Holkova</LastName><ForeName>Beata</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. bholkova@mcvh-vcu.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kmieciak</LastName><ForeName>Maciej</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perkins</LastName><ForeName>E Brent</ForeName><Initials>EB</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bose</LastName><ForeName>Prithviraj</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baz</LastName><ForeName>Rachid C</ForeName><Initials>RC</Initials><AffiliationInfo><Affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roodman</LastName><ForeName>G David</ForeName><Initials>GD</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stuart</LastName><ForeName>Robert K</ForeName><Initials>RK</Initials><AffiliationInfo><Affiliation>Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramakrishnan</LastName><ForeName>Viswanathan</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wan</LastName><ForeName>Wen</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peer</LastName><ForeName>Cody J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Center for Cancer Research, NCI, NIH, Bethesda, Maryland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dawson</LastName><ForeName>Jana</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Loveleen</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>James A. Haley Veterans' Hospital, Tampa, Florida.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Honeycutt</LastName><ForeName>Connie</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tombes</LastName><ForeName>Mary Beth</ForeName><Initials>MB</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shrader</LastName><ForeName>Ellen</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weir-Wiggins</LastName><ForeName>Caryn</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wellons</LastName><ForeName>Martha</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sankala</LastName><ForeName>Heidi</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hogan</LastName><ForeName>Kevin T</ForeName><Initials>KT</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Colevas</LastName><ForeName>A Dimitrios</ForeName><Initials>AD</Initials><AffiliationInfo><Affiliation>Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Doyle</LastName><ForeName>L Austin</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Cancer Therapy Evaluation Program, NCI, NIH, Bethesda, Maryland. Departments of.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Figg</LastName><ForeName>William D</ForeName><Initials>WD</Initials><AffiliationInfo><Affiliation>Center for Cancer Research, NCI, NIH, Bethesda, Maryland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coppola</LastName><ForeName>Domenico</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roberts</LastName><ForeName>John D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sullivan</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grant</LastName><ForeName>Steven</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>KL2 TR000057</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA93738</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>N01 HHSN261201100100C</GrantID><Agency>PHS HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HHSN261201100100C</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA100866</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 TR000058</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA093738</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA076292</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA167708</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>M01 RR000065</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 CA110953</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 CA130805</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 TR000142</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA016059</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA76292</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>KL2TR000057</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D017426">Clinical Trial, Phase I</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>09</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Clin Cancer Res</MedlineTA><NlmUniqueID>9502500</NlmUniqueID><ISSNLinking>1078-0432</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001897">Boronic Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005419">Flavonoids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010880">Piperidines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011719">Pyrazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>45AD6X575G</RegistryNumber><NameOfSubstance UI="C077990">alvocidib</NameOfSubstance></Chemical><Chemical><RegistryNumber>69G8BD63PP</RegistryNumber><NameOfSubstance 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MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001402" MajorTopicYN="N">B-Lymphocytes</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001897" MajorTopicYN="N">Boronic Acids</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000069286" MajorTopicYN="N">Bortezomib</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003131" MajorTopicYN="N">Combined Modality 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MajorTopicYN="N">Retreatment</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">NIHMS631201</OtherID><OtherID Source="NLM">PMC4233160</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>9</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>9</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>7</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25248382</ArticleId><ArticleId IdType="pii">1078-0432.CCR-14-0805</ArticleId><ArticleId IdType="doi">10.1158/1078-0432.CCR-14-0805</ArticleId><ArticleId IdType="pmc">PMC4233160</ArticleId><ArticleId 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