AustralieFrV1, Pmc, Curation, bibRecord, 002027

Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

Identifieur interne : 002027 ( Pmc/Curation ); précédent : 002026; suivant : 002028

Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

Auteurs : John M. Kirkwood [États-Unis] ; Lars Bastholt [Danemark] ; Caroline Robert [France] ; Jeff Sosman [États-Unis] ; James Larkin [Royaume-Uni] ; Peter Hersey [Australie] ; Mark Middleton [Royaume-Uni] ; Mireille Cantarini [Royaume-Uni] ; Victoria Zazulina [Royaume-Uni] ; Karin Kemsley [Royaume-Uni] ; Reinhard Dummer [Suisse]

Source :

Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2011.

RBID : PMC:3549298

Abstract

Purpose

To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma.

Experimental Design

This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m²/d for 5 days, then 23 days off-treatment). The primary endpoint was progression-free survival.

Results

Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86–1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with BRAF mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide.

Conclusions

No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549298

DOI: 10.1158/1078-0432.CCR-11-1491
PubMed: 22048237
PubMed Central: 3549298

Links toward previous steps (curation, corpus...)

to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :002176

Links to Exploration step

PMC:3549298

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma</title>
<author><name sortKey="Kirkwood, John M" sort="Kirkwood, John M" uniqKey="Kirkwood J" first="John M." last="Kirkwood">John M. Kirkwood</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Departments of Medicine and Dermatology, University of Pittsburgh</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Melanoma Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Melanoma Program, University of Pittsburgh Cancer Institute, Pittsburgh</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Bastholt, Lars" sort="Bastholt, Lars" uniqKey="Bastholt L" first="Lars" last="Bastholt">Lars Bastholt</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Department of Oncology, Odense University Hospital, Odense, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Oncology, Odense University Hospital, Odense</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Department of Medicine, Institut Gustave Roussy, Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Medicine, Institut Gustave Roussy, Villejuif</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sosman, Jeff" sort="Sosman, Jeff" uniqKey="Sosman J" first="Jeff" last="Sosman">Jeff Sosman</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Vanderbilt Ingram Cancer Center, Nash-ville, Tennessee</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Vanderbilt Ingram Cancer Center, Nash-ville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Larkin, James" sort="Larkin, James" uniqKey="Larkin J" first="James" last="Larkin">James Larkin</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Royal Marsden Hospital, Department of Medicine, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Royal Marsden Hospital, Department of Medicine, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hersey, Peter" sort="Hersey, Peter" uniqKey="Hersey P" first="Peter" last="Hersey">Peter Hersey</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Newcastle Melanoma Unit, Newcastle, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Newcastle Melanoma Unit, Newcastle, New South Wales</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Middleton, Mark" sort="Middleton, Mark" uniqKey="Middleton M" first="Mark" last="Middleton">Mark Middleton</name>
<affiliation wicri:level="3"><nlm:aff id="A8">NIHR Biomedical Research Centre, Churchill Hospital, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>NIHR Biomedical Research Centre, Churchill Hospital</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Cantarini, Mireille" sort="Cantarini, Mireille" uniqKey="Cantarini M" first="Mireille" last="Cantarini">Mireille Cantarini</name>
<affiliation wicri:level="1"><nlm:aff id="A9">AstraZeneca, Alderley Park, Macclesfield, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>AstraZeneca, Alderley Park, Macclesfield</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zazulina, Victoria" sort="Zazulina, Victoria" uniqKey="Zazulina V" first="Victoria" last="Zazulina">Victoria Zazulina</name>
<affiliation wicri:level="1"><nlm:aff id="A9">AstraZeneca, Alderley Park, Macclesfield, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>AstraZeneca, Alderley Park, Macclesfield</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kemsley, Karin" sort="Kemsley, Karin" uniqKey="Kemsley K" first="Karin" last="Kemsley">Karin Kemsley</name>
<affiliation wicri:level="1"><nlm:aff id="A9">AstraZeneca, Alderley Park, Macclesfield, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>AstraZeneca, Alderley Park, Macclesfield</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dummer, Reinhard" sort="Dummer, Reinhard" uniqKey="Dummer R" first="Reinhard" last="Dummer">Reinhard Dummer</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Dermatology, Zürich University Hospital, Zürich, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Dermatology, Zürich University Hospital, Zürich</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22048237</idno>
<idno type="pmc">3549298</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549298</idno>
<idno type="RBID">PMC:3549298</idno>
<idno type="doi">10.1158/1078-0432.CCR-11-1491</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">002176</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002176</idno>
<idno type="wicri:Area/Pmc/Curation">002027</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002027</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma</title>
<author><name sortKey="Kirkwood, John M" sort="Kirkwood, John M" uniqKey="Kirkwood J" first="John M." last="Kirkwood">John M. Kirkwood</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Departments of Medicine and Dermatology, University of Pittsburgh</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Melanoma Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Melanoma Program, University of Pittsburgh Cancer Institute, Pittsburgh</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Bastholt, Lars" sort="Bastholt, Lars" uniqKey="Bastholt L" first="Lars" last="Bastholt">Lars Bastholt</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Department of Oncology, Odense University Hospital, Odense, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Oncology, Odense University Hospital, Odense</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Department of Medicine, Institut Gustave Roussy, Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Medicine, Institut Gustave Roussy, Villejuif</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sosman, Jeff" sort="Sosman, Jeff" uniqKey="Sosman J" first="Jeff" last="Sosman">Jeff Sosman</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Vanderbilt Ingram Cancer Center, Nash-ville, Tennessee</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Vanderbilt Ingram Cancer Center, Nash-ville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Larkin, James" sort="Larkin, James" uniqKey="Larkin J" first="James" last="Larkin">James Larkin</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Royal Marsden Hospital, Department of Medicine, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Royal Marsden Hospital, Department of Medicine, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hersey, Peter" sort="Hersey, Peter" uniqKey="Hersey P" first="Peter" last="Hersey">Peter Hersey</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Newcastle Melanoma Unit, Newcastle, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Newcastle Melanoma Unit, Newcastle, New South Wales</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Middleton, Mark" sort="Middleton, Mark" uniqKey="Middleton M" first="Mark" last="Middleton">Mark Middleton</name>
<affiliation wicri:level="3"><nlm:aff id="A8">NIHR Biomedical Research Centre, Churchill Hospital, Oxford</nlm:aff>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
</placeName>
<wicri:orgArea>NIHR Biomedical Research Centre, Churchill Hospital</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Cantarini, Mireille" sort="Cantarini, Mireille" uniqKey="Cantarini M" first="Mireille" last="Cantarini">Mireille Cantarini</name>
<affiliation wicri:level="1"><nlm:aff id="A9">AstraZeneca, Alderley Park, Macclesfield, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>AstraZeneca, Alderley Park, Macclesfield</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zazulina, Victoria" sort="Zazulina, Victoria" uniqKey="Zazulina V" first="Victoria" last="Zazulina">Victoria Zazulina</name>
<affiliation wicri:level="1"><nlm:aff id="A9">AstraZeneca, Alderley Park, Macclesfield, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>AstraZeneca, Alderley Park, Macclesfield</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kemsley, Karin" sort="Kemsley, Karin" uniqKey="Kemsley K" first="Karin" last="Kemsley">Karin Kemsley</name>
<affiliation wicri:level="1"><nlm:aff id="A9">AstraZeneca, Alderley Park, Macclesfield, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>AstraZeneca, Alderley Park, Macclesfield</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dummer, Reinhard" sort="Dummer, Reinhard" uniqKey="Dummer R" first="Reinhard" last="Dummer">Reinhard Dummer</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Dermatology, Zürich University Hospital, Zürich, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Dermatology, Zürich University Hospital, Zürich</wicri:regionArea>
</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="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title>
<p id="P1">To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma.</p>
</sec>
<sec id="S2"><title>Experimental Design</title>
<p id="P2">This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m<sup>2</sup>
/d for 5 days, then 23 days off-treatment). The primary endpoint was progression-free survival.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86–1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with <italic>BRAF</italic>
 mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were <italic>BRAF</italic>
 mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for <italic>BRAF/NRAS</italic>
 mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had <italic>BRAF</italic>
 mutant tumors.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">9502500</journal-id>
<journal-id journal-id-type="pubmed-jr-id">8794</journal-id>
<journal-id journal-id-type="nlm-ta">Clin Cancer Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin. Cancer Res.</journal-id>
<journal-title-group><journal-title>Clinical cancer research : an official journal of the American Association for Cancer Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">1078-0432</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22048237</article-id>
<article-id pub-id-type="pmc">3549298</article-id>
<article-id pub-id-type="doi">10.1158/1078-0432.CCR-11-1491</article-id>
<article-id pub-id-type="manuscript">NIHMS431914</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kirkwood</surname>
<given-names>John M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bastholt</surname>
<given-names>Lars</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Robert</surname>
<given-names>Caroline</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sosman</surname>
<given-names>Jeff</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Larkin</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hersey</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Middleton</surname>
<given-names>Mark</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cantarini</surname>
<given-names>Mireille</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zazulina</surname>
<given-names>Victoria</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kemsley</surname>
<given-names>Karin</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dummer</surname>
<given-names>Reinhard</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Departments of Medicine and Dermatology, University of Pittsburgh</aff>
<aff id="A2"><label>2</label>
Melanoma Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania</aff>
<aff id="A3"><label>3</label>
Department of Oncology, Odense University Hospital, Odense, Denmark</aff>
<aff id="A4"><label>4</label>
Department of Medicine, Institut Gustave Roussy, Villejuif, France</aff>
<aff id="A5"><label>5</label>
Vanderbilt Ingram Cancer Center, Nash-ville, Tennessee</aff>
<aff id="A6"><label>6</label>
Royal Marsden Hospital, Department of Medicine, London, United Kingdom</aff>
<aff id="A7"><label>7</label>
Newcastle Melanoma Unit, Newcastle, New South Wales, Australia</aff>
<aff id="A8"><label>8</label>
NIHR Biomedical Research Centre, Churchill Hospital, Oxford</aff>
<aff id="A9"><label>9</label>
AstraZeneca, Alderley Park, Macclesfield, United Kingdom</aff>
<aff id="A10"><label>10</label>
Department of Dermatology, Zürich University Hospital, Zürich, Switzerland</aff>
<author-notes><corresp id="CR1"><bold>Corresponding Author:</bold>
 John M. Kirkwood, Melanoma Program, University of Pittsburgh Cancer Institute, HCC Suite 1.32, 5117 Center Avenue, Pittsburgh, PA 15213. Phone: 412-623-7707; Fax: 412-623-7704; <email>KirkwoodJM@upmc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>11</day>
<month>1</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>02</day>
<month>11</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><day>15</day>
<month>1</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>19</day>
<month>1</month>
<year>2013</year>
</pub-date>
<volume>18</volume>
<issue>2</issue>
<fpage>555</fpage>
<lpage>567</lpage>
<permissions><copyright-statement>Copyright © 2012 American Association for Cancer Research</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<abstract><sec id="S1"><title>Purpose</title>
<p id="P1">To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma.</p>
</sec>
<sec id="S2"><title>Experimental Design</title>
<p id="P2">This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m<sup>2</sup>
/d for 5 days, then 23 days off-treatment). The primary endpoint was progression-free survival.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86–1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with <italic>BRAF</italic>
 mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were <italic>BRAF</italic>
 mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for <italic>BRAF/NRAS</italic>
 mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had <italic>BRAF</italic>
 mutant tumors.</p>
</sec>
</abstract>
<funding-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source>
<award-id>K24 CA097588 || CA</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Curation

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002027 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 002027 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Pmc
   |étape=   Curation
   |type=    RBID
   |clé=     PMC:3549298
   |texte=   Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i   -Sk "pubmed:22048237" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Dec 5 10:43:12 2017. Site generation: Tue Mar 5 14:07:20 2024

	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur les relations entre la France et l'Australie

Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

Source :

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki