Phase Ib/II study of hydroxychloroquine in combination with chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC).
Identifieur interne : 000A31 ( Ncbi/Merge ); précédent : 000A30; suivant : 000A32Phase Ib/II study of hydroxychloroquine in combination with chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC).
Auteurs : Jyoti Malhotra [États-Unis] ; Salma Jabbour [États-Unis] ; Michelle Orlick [États-Unis] ; Gregory Riedlinger [États-Unis] ; Yanxiang Guo [États-Unis] ; Eileen White [États-Unis] ; Joseph Aisner [États-Unis]Source :
- Cancer treatment and research communications [ 2468-2942 ] ; 2019.
Abstract
Activation of cell survival pathways such as autophagy represents a potential resistance mechanism to chemotherapy in NSCLC. Preclinical studies report that autophagy inhibition suppresses lung tumor development and progression. We report the safety and efficacy for adding autophagy inhibitor, hydroxychloroquine, to chemotherapy in a phase Ib/II single-arm study in patients with metastatic NSCLC.
DOI: 10.1016/j.ctarc.2019.100158
PubMed: 31521049
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Electronic address: jyoti.malhotra@rutgers.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Jabbour, Salma" sort="Jabbour, Salma" uniqKey="Jabbour S" first="Salma" last="Jabbour">Salma Jabbour</name><affiliation wicri:level="2"><nlm:affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Orlick, Michelle" sort="Orlick, Michelle" uniqKey="Orlick M" first="Michelle" last="Orlick">Michelle Orlick</name><affiliation wicri:level="2"><nlm:affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Riedlinger, Gregory" sort="Riedlinger, Gregory" uniqKey="Riedlinger G" first="Gregory" last="Riedlinger">Gregory Riedlinger</name><affiliation wicri:level="2"><nlm:affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Guo, Yanxiang" sort="Guo, Yanxiang" uniqKey="Guo Y" first="Yanxiang" last="Guo">Yanxiang Guo</name><affiliation wicri:level="2"><nlm:affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="White, Eileen" sort="White, Eileen" uniqKey="White E" first="Eileen" last="White">Eileen White</name><affiliation wicri:level="2"><nlm:affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Aisner, Joseph" sort="Aisner, Joseph" uniqKey="Aisner J" first="Joseph" last="Aisner">Joseph Aisner</name><affiliation wicri:level="2"><nlm:affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author></analytic><series><title level="j">Cancer treatment and research communications</title><idno type="eISSN">2468-2942</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Activation of cell survival pathways such as autophagy represents a potential resistance mechanism to chemotherapy in NSCLC. Preclinical studies report that autophagy inhibition suppresses lung tumor development and progression. We report the safety and efficacy for adding autophagy inhibitor, hydroxychloroquine, to chemotherapy in a phase Ib/II single-arm study in patients with metastatic NSCLC.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">31521049</PMID><DateRevised><Year>2020</Year><Month>02</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2468-2942</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><PubDate><Year>2019</Year></PubDate></JournalIssue><Title>Cancer treatment and research communications</Title><ISOAbbreviation>Cancer Treat Res Commun</ISOAbbreviation></Journal><ArticleTitle>Phase Ib/II study of hydroxychloroquine in combination with chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC).</ArticleTitle><Pagination><MedlinePgn>100158</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2468-2942(19)30154-6</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ctarc.2019.100158</ELocationID><Abstract><AbstractText Label="OBJECTIVES">Activation of cell survival pathways such as autophagy represents a potential resistance mechanism to chemotherapy in NSCLC. Preclinical studies report that autophagy inhibition suppresses lung tumor development and progression. We report the safety and efficacy for adding autophagy inhibitor, hydroxychloroquine, to chemotherapy in a phase Ib/II single-arm study in patients with metastatic NSCLC.</AbstractText><AbstractText Label="PATIENTS AND METHODS">We treated patients with untreated metastatic NSCLC with carboplatin, paclitaxel (and bevacizumab if criteria met) and hydroxychloroquine 200 mg BID. Patients continued on hydroxychloroquine (+/- bevacizumab) maintenance after 4-6 cycles of therapy.</AbstractText><AbstractText Label="RESULTS">We enrolled 40 patients, 8 on phase Ib and 32 on phase II. Forty-three percent were female; 50% with squamous histology. Median age was 62 years (range, 43-73). Thirteen patients developed ≥grade 3 treatment-related adverse event. Common adverse events (all grades) were neutropenia (35%), neuropathy (32.5%), and anemia (32.5%). The objective response rate (ORR) was 33% in the 30 patients (phase II) evaluable for response. Additionally, 20% of the patients demonstrated stable disease (clinical benefit rate of 53%). The median PFS was 3.3 months (95% CI 2.1-6.8 months). In 9 patients with KRAS positive tumors, ORR was 44% and median PFS was higher than expected at 6.4 months (95% CI 1.8-15.6).</AbstractText><AbstractText Label="CONCLUSIONS">Addition of hydroxychloroquine is safe and tolerable with a modest improvement in clinical responses compared to prior studies. Autophagy inhibition may overcome chemotherapy resistance in advanced NSCLC and further study in a more molecularly selected population such as KRAS-positive tumors is warranted.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Malhotra</LastName><ForeName>Jyoti</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA. Electronic address: jyoti.malhotra@rutgers.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jabbour</LastName><ForeName>Salma</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Orlick</LastName><ForeName>Michelle</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Riedlinger</LastName><ForeName>Gregory</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Yanxiang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>White</LastName><ForeName>Eileen</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aisner</LastName><ForeName>Joseph</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195, Little Albany street, New Brunswick, NJ 08903, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>09</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Cancer Treat Res Commun</MedlineTA><NlmUniqueID>101694651</NlmUniqueID><ISSNLinking>2468-2942</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Autophagy</Keyword><Keyword MajorTopicYN="Y">Hydroxychloroquine</Keyword><Keyword MajorTopicYN="Y">Lung cancer</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>07</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>08</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>09</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>9</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31521049</ArticleId><ArticleId IdType="pii">S2468-2942(19)30154-6</ArticleId><ArticleId IdType="doi">10.1016/j.ctarc.2019.100158</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>New Jersey</li></region></list><tree><country name="États-Unis"><region name="New Jersey"><name sortKey="Malhotra, Jyoti" sort="Malhotra, Jyoti" uniqKey="Malhotra J" first="Jyoti" last="Malhotra">Jyoti Malhotra</name></region><name sortKey="Aisner, Joseph" sort="Aisner, Joseph" uniqKey="Aisner J" first="Joseph" last="Aisner">Joseph Aisner</name><name sortKey="Guo, Yanxiang" sort="Guo, Yanxiang" uniqKey="Guo Y" first="Yanxiang" last="Guo">Yanxiang Guo</name><name sortKey="Jabbour, Salma" sort="Jabbour, Salma" uniqKey="Jabbour S" first="Salma" last="Jabbour">Salma Jabbour</name><name sortKey="Orlick, Michelle" sort="Orlick, Michelle" uniqKey="Orlick M" first="Michelle" last="Orlick">Michelle Orlick</name><name sortKey="Riedlinger, Gregory" sort="Riedlinger, Gregory" uniqKey="Riedlinger G" first="Gregory" last="Riedlinger">Gregory Riedlinger</name><name sortKey="White, Eileen" sort="White, Eileen" uniqKey="White E" first="Eileen" last="White">Eileen White</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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