A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors
Purpose MN-029 (denibulin HCl) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. This study determined the safety, pharmacokinetics, and acute anti-vascular effects of MN-029. Methods P...
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creator | Ricart, Alejandro D. Ashton, Edward A. Cooney, Matthew M. Sarantopoulos, John Brell, Joanna M. Feldman, Maria A. Ruby, Kale E. Matsuda, Kazuko Munsey, Mark S. Medina, Gerardo Zambito, Angela Tolcher, Anthony W. Remick, Scot C. |
description | Purpose
MN-029 (denibulin HCl) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. This study determined the safety, pharmacokinetics, and acute anti-vascular effects of MN-029.
Methods
Patients were treated with escalating doses of MN-029 (4.0–225 mg/m
2
) administered IV at 3-week intervals. This first-in-human study followed an accelerated titration design, with intra-patient dose escalation. Plasma samples were assayed to determine PK parameters. DCE-MRI scans were acquired at baseline and at 6–8 h post-dose.
Results
Thirty-four patients received 151 infusions of MN-029. The most common toxicities of MN-029 included nausea and vomiting (which appeared to be dose related), diarrhea, fatigue, headache, and anorexia. No clinically significant myelotoxicity, stomatitis or alopecia was observed. There was no evidence of cumulative toxicity in patients receiving multiple courses of therapy. The cohort at 180 mg/m
2
was expanded to six patients due to a reversible episode of acute coronary ischemia, without sequelae and with preservation of myocardial function. Two dose-limiting toxicities occurred at 225 mg/m
2
, a transient ischemic attack and grade 3 transaminitis, thus ending dose escalation. Pharmacokinetic data indicated dose-related increases in
C
max
and AUC values, although substantial inter-subject variability was observed. No objective responses were noted; however, five patients had stable disease ≥6 months. A significant linear correlation was found between reduction in
K
trans
and exposure to MN-029.
Conclusions
MN-029 was generally well tolerated and showed decrease in tumor vascular parameters. The maximum tolerated dose was 180 mg/m
2
. |
doi_str_mv | 10.1007/s00280-011-1565-4 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_894161469</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2468968991</sourcerecordid><originalsourceid>FETCH-LOGICAL-c400t-3fe12c348851d3b30d2ecf77b86706b00e3f568500b1edf644ca853aad117b183</originalsourceid><addsrcrecordid>eNp1kUtr3DAQgEVpaTab_IBeiigUUoiSGUuWtccQkmYhj0t7FrIl72rxyq5kb8m_j8Juk1NPMzDfPPiGkC8IFwhQXSaAQgEDRIalLJn4QGYoeMFACf6RzIALwcoKxBE5TmkDAAI5_0yOCuRQFguYkeGKDmuTHF3SNE72mfYtfXhkUCzomXXB11Pnw49zamjod66jO5OaqTORWZ_iNIw-rKhZuTCeUx_oYEaf80T_-nFNjd2Z0DhLU995S8dp28d0Qj61pkvu9BDn5Pftza_rO3b_9HN5fXXPGgEwMt46LBoulCrR8pqDLVzTVlWtZAWyBnC8LaUqAWp0tpVCNEaV3BiLWNWo-Jx8288dYv9ncmnUm36KIa_UaiFQopCLDOEeamKfUnStHqLfmvisEfSrYr1XrLNi_apYi9zz9TB4qrfOvnX8c5qB7wcguzJdG7MEn945kT8iJc9csedSLoWVi-8X_n_7C0T2kcI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>894161469</pqid></control><display><type>article</type><title>A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Ricart, Alejandro D. ; Ashton, Edward A. ; Cooney, Matthew M. ; Sarantopoulos, John ; Brell, Joanna M. ; Feldman, Maria A. ; Ruby, Kale E. ; Matsuda, Kazuko ; Munsey, Mark S. ; Medina, Gerardo ; Zambito, Angela ; Tolcher, Anthony W. ; Remick, Scot C.</creator><creatorcontrib>Ricart, Alejandro D. ; Ashton, Edward A. ; Cooney, Matthew M. ; Sarantopoulos, John ; Brell, Joanna M. ; Feldman, Maria A. ; Ruby, Kale E. ; Matsuda, Kazuko ; Munsey, Mark S. ; Medina, Gerardo ; Zambito, Angela ; Tolcher, Anthony W. ; Remick, Scot C.</creatorcontrib><description>Purpose
MN-029 (denibulin HCl) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. This study determined the safety, pharmacokinetics, and acute anti-vascular effects of MN-029.
Methods
Patients were treated with escalating doses of MN-029 (4.0–225 mg/m
2
) administered IV at 3-week intervals. This first-in-human study followed an accelerated titration design, with intra-patient dose escalation. Plasma samples were assayed to determine PK parameters. DCE-MRI scans were acquired at baseline and at 6–8 h post-dose.
Results
Thirty-four patients received 151 infusions of MN-029. The most common toxicities of MN-029 included nausea and vomiting (which appeared to be dose related), diarrhea, fatigue, headache, and anorexia. No clinically significant myelotoxicity, stomatitis or alopecia was observed. There was no evidence of cumulative toxicity in patients receiving multiple courses of therapy. The cohort at 180 mg/m
2
was expanded to six patients due to a reversible episode of acute coronary ischemia, without sequelae and with preservation of myocardial function. Two dose-limiting toxicities occurred at 225 mg/m
2
, a transient ischemic attack and grade 3 transaminitis, thus ending dose escalation. Pharmacokinetic data indicated dose-related increases in
C
max
and AUC values, although substantial inter-subject variability was observed. No objective responses were noted; however, five patients had stable disease ≥6 months. A significant linear correlation was found between reduction in
K
trans
and exposure to MN-029.
Conclusions
MN-029 was generally well tolerated and showed decrease in tumor vascular parameters. The maximum tolerated dose was 180 mg/m
2
.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-011-1565-4</identifier><identifier>PMID: 21305290</identifier><identifier>CODEN: CCPHDZ</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adult ; Aged ; Antineoplastic agents ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacology ; Area Under Curve ; Benzimidazoles - administration & dosage ; Benzimidazoles - adverse effects ; Benzimidazoles - pharmacology ; Biological and medical sciences ; Cancer Research ; Dose-Response Relationship, Drug ; Female ; Humans ; Magnetic Resonance Imaging - methods ; Male ; Maximum Tolerated Dose ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasms - drug therapy ; Neoplasms - pathology ; Oncology ; Original Article ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Tumors</subject><ispartof>Cancer chemotherapy and pharmacology, 2011-10, Vol.68 (4), p.959-970</ispartof><rights>Springer-Verlag 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-3fe12c348851d3b30d2ecf77b86706b00e3f568500b1edf644ca853aad117b183</citedby><cites>FETCH-LOGICAL-c400t-3fe12c348851d3b30d2ecf77b86706b00e3f568500b1edf644ca853aad117b183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00280-011-1565-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-011-1565-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24570663$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21305290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ricart, Alejandro D.</creatorcontrib><creatorcontrib>Ashton, Edward A.</creatorcontrib><creatorcontrib>Cooney, Matthew M.</creatorcontrib><creatorcontrib>Sarantopoulos, John</creatorcontrib><creatorcontrib>Brell, Joanna M.</creatorcontrib><creatorcontrib>Feldman, Maria A.</creatorcontrib><creatorcontrib>Ruby, Kale E.</creatorcontrib><creatorcontrib>Matsuda, Kazuko</creatorcontrib><creatorcontrib>Munsey, Mark S.</creatorcontrib><creatorcontrib>Medina, Gerardo</creatorcontrib><creatorcontrib>Zambito, Angela</creatorcontrib><creatorcontrib>Tolcher, Anthony W.</creatorcontrib><creatorcontrib>Remick, Scot C.</creatorcontrib><title>A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Purpose
MN-029 (denibulin HCl) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. This study determined the safety, pharmacokinetics, and acute anti-vascular effects of MN-029.
Methods
Patients were treated with escalating doses of MN-029 (4.0–225 mg/m
2
) administered IV at 3-week intervals. This first-in-human study followed an accelerated titration design, with intra-patient dose escalation. Plasma samples were assayed to determine PK parameters. DCE-MRI scans were acquired at baseline and at 6–8 h post-dose.
Results
Thirty-four patients received 151 infusions of MN-029. The most common toxicities of MN-029 included nausea and vomiting (which appeared to be dose related), diarrhea, fatigue, headache, and anorexia. No clinically significant myelotoxicity, stomatitis or alopecia was observed. There was no evidence of cumulative toxicity in patients receiving multiple courses of therapy. The cohort at 180 mg/m
2
was expanded to six patients due to a reversible episode of acute coronary ischemia, without sequelae and with preservation of myocardial function. Two dose-limiting toxicities occurred at 225 mg/m
2
, a transient ischemic attack and grade 3 transaminitis, thus ending dose escalation. Pharmacokinetic data indicated dose-related increases in
C
max
and AUC values, although substantial inter-subject variability was observed. No objective responses were noted; however, five patients had stable disease ≥6 months. A significant linear correlation was found between reduction in
K
trans
and exposure to MN-029.
Conclusions
MN-029 was generally well tolerated and showed decrease in tumor vascular parameters. The maximum tolerated dose was 180 mg/m
2
.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Area Under Curve</subject><subject>Benzimidazoles - administration & dosage</subject><subject>Benzimidazoles - adverse effects</subject><subject>Benzimidazoles - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cancer Research</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Maximum Tolerated Dose</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Tumors</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kUtr3DAQgEVpaTab_IBeiigUUoiSGUuWtccQkmYhj0t7FrIl72rxyq5kb8m_j8Juk1NPMzDfPPiGkC8IFwhQXSaAQgEDRIalLJn4QGYoeMFACf6RzIALwcoKxBE5TmkDAAI5_0yOCuRQFguYkeGKDmuTHF3SNE72mfYtfXhkUCzomXXB11Pnw49zamjod66jO5OaqTORWZ_iNIw-rKhZuTCeUx_oYEaf80T_-nFNjd2Z0DhLU995S8dp28d0Qj61pkvu9BDn5Pftza_rO3b_9HN5fXXPGgEwMt46LBoulCrR8pqDLVzTVlWtZAWyBnC8LaUqAWp0tpVCNEaV3BiLWNWo-Jx8288dYv9ncmnUm36KIa_UaiFQopCLDOEeamKfUnStHqLfmvisEfSrYr1XrLNi_apYi9zz9TB4qrfOvnX8c5qB7wcguzJdG7MEn945kT8iJc9csedSLoWVi-8X_n_7C0T2kcI</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>Ricart, Alejandro D.</creator><creator>Ashton, Edward A.</creator><creator>Cooney, Matthew M.</creator><creator>Sarantopoulos, John</creator><creator>Brell, Joanna M.</creator><creator>Feldman, Maria A.</creator><creator>Ruby, Kale E.</creator><creator>Matsuda, Kazuko</creator><creator>Munsey, Mark S.</creator><creator>Medina, Gerardo</creator><creator>Zambito, Angela</creator><creator>Tolcher, Anthony W.</creator><creator>Remick, Scot C.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20111001</creationdate><title>A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors</title><author>Ricart, Alejandro D. ; Ashton, Edward A. ; Cooney, Matthew M. ; Sarantopoulos, John ; Brell, Joanna M. ; Feldman, Maria A. ; Ruby, Kale E. ; Matsuda, Kazuko ; Munsey, Mark S. ; Medina, Gerardo ; Zambito, Angela ; Tolcher, Anthony W. ; Remick, Scot C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-3fe12c348851d3b30d2ecf77b86706b00e3f568500b1edf644ca853aad117b183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Area Under Curve</topic><topic>Benzimidazoles - administration & dosage</topic><topic>Benzimidazoles - adverse effects</topic><topic>Benzimidazoles - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cancer Research</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Male</topic><topic>Maximum Tolerated Dose</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - pathology</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ricart, Alejandro D.</creatorcontrib><creatorcontrib>Ashton, Edward A.</creatorcontrib><creatorcontrib>Cooney, Matthew M.</creatorcontrib><creatorcontrib>Sarantopoulos, John</creatorcontrib><creatorcontrib>Brell, Joanna M.</creatorcontrib><creatorcontrib>Feldman, Maria A.</creatorcontrib><creatorcontrib>Ruby, Kale E.</creatorcontrib><creatorcontrib>Matsuda, Kazuko</creatorcontrib><creatorcontrib>Munsey, Mark S.</creatorcontrib><creatorcontrib>Medina, Gerardo</creatorcontrib><creatorcontrib>Zambito, Angela</creatorcontrib><creatorcontrib>Tolcher, Anthony W.</creatorcontrib><creatorcontrib>Remick, Scot C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ricart, Alejandro D.</au><au>Ashton, Edward A.</au><au>Cooney, Matthew M.</au><au>Sarantopoulos, John</au><au>Brell, Joanna M.</au><au>Feldman, Maria A.</au><au>Ruby, Kale E.</au><au>Matsuda, Kazuko</au><au>Munsey, Mark S.</au><au>Medina, Gerardo</au><au>Zambito, Angela</au><au>Tolcher, Anthony W.</au><au>Remick, Scot C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>68</volume><issue>4</issue><spage>959</spage><epage>970</epage><pages>959-970</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><coden>CCPHDZ</coden><abstract>Purpose
MN-029 (denibulin HCl) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. This study determined the safety, pharmacokinetics, and acute anti-vascular effects of MN-029.
Methods
Patients were treated with escalating doses of MN-029 (4.0–225 mg/m
2
) administered IV at 3-week intervals. This first-in-human study followed an accelerated titration design, with intra-patient dose escalation. Plasma samples were assayed to determine PK parameters. DCE-MRI scans were acquired at baseline and at 6–8 h post-dose.
Results
Thirty-four patients received 151 infusions of MN-029. The most common toxicities of MN-029 included nausea and vomiting (which appeared to be dose related), diarrhea, fatigue, headache, and anorexia. No clinically significant myelotoxicity, stomatitis or alopecia was observed. There was no evidence of cumulative toxicity in patients receiving multiple courses of therapy. The cohort at 180 mg/m
2
was expanded to six patients due to a reversible episode of acute coronary ischemia, without sequelae and with preservation of myocardial function. Two dose-limiting toxicities occurred at 225 mg/m
2
, a transient ischemic attack and grade 3 transaminitis, thus ending dose escalation. Pharmacokinetic data indicated dose-related increases in
C
max
and AUC values, although substantial inter-subject variability was observed. No objective responses were noted; however, five patients had stable disease ≥6 months. A significant linear correlation was found between reduction in
K
trans
and exposure to MN-029.
Conclusions
MN-029 was generally well tolerated and showed decrease in tumor vascular parameters. The maximum tolerated dose was 180 mg/m
2
.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>21305290</pmid><doi>10.1007/s00280-011-1565-4</doi><tpages>12</tpages></addata></record> |
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subjects | Adult Aged Antineoplastic agents Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacology Area Under Curve Benzimidazoles - administration & dosage Benzimidazoles - adverse effects Benzimidazoles - pharmacology Biological and medical sciences Cancer Research Dose-Response Relationship, Drug Female Humans Magnetic Resonance Imaging - methods Male Maximum Tolerated Dose Medical sciences Medicine Medicine & Public Health Middle Aged Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasms - drug therapy Neoplasms - pathology Oncology Original Article Pharmacology. Drug treatments Pharmacology/Toxicology Tumors |
title | A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors |
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