Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)
Abstract Background Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone. Me...
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| Veröffentlicht in: | Neuro-oncology (Charlottesville, Va.) Va.), 2022-07, Vol.24 (7), p.1178-1190 |
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| creator | Leary, Sarah E S Kilburn, Lindsay Geyer, J Russell Kocak, Mehmet Huang, Jie Smith, Kyle S Hadley, Jennifer Ermoian, Ralph MacDonald, Tobey J Goldman, Stewart Phillips, Peter Young Poussaint, Tina Olson, James M Ellison, David W Dunkel, Ira J Fouladi, Maryam Onar-Thomas, Arzu Northcott, Paul A |
| description | Abstract
Background
Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone.
Methods
PBTC-026 was a prospective multi-institutional clinical trial for children |
| doi_str_mv | 10.1093/neuonc/noab293 |
| format | Article |
| fullrecord | <record><control><sourceid>oup_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9248403</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/neuonc/noab293</oup_id><sourcerecordid>10.1093/neuonc/noab293</sourcerecordid><originalsourceid>FETCH-LOGICAL-c424t-b024cef8e6a48e9f31133f33a1db27a1408a74e1caa9bdb139801936b971959f3</originalsourceid><addsrcrecordid>eNqFkc1OGzEUha2qVQmUbZfIy2Yx4L_5cReVkgjaSpHIImU7up7xEKOMPbI9VHmVPi0OSRGsWN2r4-9-XhyEvlJySYnkV1aPzjZX1oFikn9AE5oznuVVUXx83llW5bQ8QachPBDCaF7Qz-iEC8lzWZQT9O_OeWNdiBAx2Bab4KLXMUXG4r8mbnCz0b2LG-1h2OEU7txo71Nqtq3XR0b3yu-chS1WHhITx9758B3PsNeD8xF33vU4SfBKtwaiNw2eP5PrPYkXzoaEmbHH31bz9SIjrJh-QZ862AZ9fpxn6M_N9XrxK1ve_vy9mC2zRjARM0WYaHRX6QJEpWXHKeW84xxoq1gJVJAKSqFpAyBVqyiXFaGSF0qWVOaJP0M_Dt5hVL1uG22jh209eNOD39UOTP32xZpNfe8ea8lEJQhPgsuDoPEuBK-7l1tK6n1L9aGl-thSOrh4_eML_r-WBEwPgBuH92RP4LKi8g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Leary, Sarah E S ; Kilburn, Lindsay ; Geyer, J Russell ; Kocak, Mehmet ; Huang, Jie ; Smith, Kyle S ; Hadley, Jennifer ; Ermoian, Ralph ; MacDonald, Tobey J ; Goldman, Stewart ; Phillips, Peter ; Young Poussaint, Tina ; Olson, James M ; Ellison, David W ; Dunkel, Ira J ; Fouladi, Maryam ; Onar-Thomas, Arzu ; Northcott, Paul A</creator><creatorcontrib>Leary, Sarah E S ; Kilburn, Lindsay ; Geyer, J Russell ; Kocak, Mehmet ; Huang, Jie ; Smith, Kyle S ; Hadley, Jennifer ; Ermoian, Ralph ; MacDonald, Tobey J ; Goldman, Stewart ; Phillips, Peter ; Young Poussaint, Tina ; Olson, James M ; Ellison, David W ; Dunkel, Ira J ; Fouladi, Maryam ; Onar-Thomas, Arzu ; Northcott, Paul A</creatorcontrib><description>Abstract
Background
Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone.
Methods
PBTC-026 was a prospective multi-institutional clinical trial for children <48 months of age with newly diagnosed embryonal tumors of the CNS. Treatment included three 21-day cycles of induction therapy with vorinostat and isotretinoin, cisplatin, vincristine, cyclophosphamide, and etoposide; three 28-day cycles of consolidation therapy with carboplatin and thiotepa followed by stem cell rescue; and twelve 28-day cycles of maintenance therapy with vorinostat and isotretinoin. Patients with M0 medulloblastoma (MB) received focal radiation following consolidation therapy. Molecular classification was by DNA methylation array.
Results
Thirty-one patients with median age of 26 months (range 6-46) received treatment on study; 19 (61%) were male. Diagnosis was MB in 20 and supratentorial CNS embryonal tumor in 11. 24/31 patients completed induction therapy within a pre-specified feasibility window of 98 days. Five-year progression-free survival (PFS) and overall survival (OS) for all 31 patients were 55 ± 15 and 61 ± 13, respectively. Five-year PFS was 42 ± 13 for group 3 MB (n = 12); 80 ± 25 for SHH MB (n = 5); 33 ± 19 for embryonal tumor with multilayered rosettes (ETMR, n = 6).
Conclusion
It was safe and feasible to incorporate vorinostat and isotretinoin into an intensive chemotherapy regimen. Further study to define efficacy in this high-risk group of patients is warranted.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noab293</identifier><identifier>PMID: 34935967</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Brain Neoplasms - pathology ; Cerebellar Neoplasms - drug therapy ; Child ; Child, Preschool ; Cyclophosphamide ; Etoposide ; Female ; Humans ; Infant ; Isotretinoin - therapeutic use ; Male ; Medulloblastoma - pathology ; Neoplasms, Germ Cell and Embryonal - drug therapy ; Neuroectodermal Tumors, Primitive - drug therapy ; Pediatric Neuro-Oncology ; Prospective Studies ; Vincristine ; Vorinostat</subject><ispartof>Neuro-oncology (Charlottesville, Va.), 2022-07, Vol.24 (7), p.1178-1190</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-b024cef8e6a48e9f31133f33a1db27a1408a74e1caa9bdb139801936b971959f3</citedby><cites>FETCH-LOGICAL-c424t-b024cef8e6a48e9f31133f33a1db27a1408a74e1caa9bdb139801936b971959f3</cites><orcidid>0000-0003-0225-6184 ; 0000-0002-5693-035X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248403/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248403/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1578,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34935967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leary, Sarah E S</creatorcontrib><creatorcontrib>Kilburn, Lindsay</creatorcontrib><creatorcontrib>Geyer, J Russell</creatorcontrib><creatorcontrib>Kocak, Mehmet</creatorcontrib><creatorcontrib>Huang, Jie</creatorcontrib><creatorcontrib>Smith, Kyle S</creatorcontrib><creatorcontrib>Hadley, Jennifer</creatorcontrib><creatorcontrib>Ermoian, Ralph</creatorcontrib><creatorcontrib>MacDonald, Tobey J</creatorcontrib><creatorcontrib>Goldman, Stewart</creatorcontrib><creatorcontrib>Phillips, Peter</creatorcontrib><creatorcontrib>Young Poussaint, Tina</creatorcontrib><creatorcontrib>Olson, James M</creatorcontrib><creatorcontrib>Ellison, David W</creatorcontrib><creatorcontrib>Dunkel, Ira J</creatorcontrib><creatorcontrib>Fouladi, Maryam</creatorcontrib><creatorcontrib>Onar-Thomas, Arzu</creatorcontrib><creatorcontrib>Northcott, Paul A</creatorcontrib><title>Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)</title><title>Neuro-oncology (Charlottesville, Va.)</title><addtitle>Neuro Oncol</addtitle><description>Abstract
Background
Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone.
Methods
PBTC-026 was a prospective multi-institutional clinical trial for children <48 months of age with newly diagnosed embryonal tumors of the CNS. Treatment included three 21-day cycles of induction therapy with vorinostat and isotretinoin, cisplatin, vincristine, cyclophosphamide, and etoposide; three 28-day cycles of consolidation therapy with carboplatin and thiotepa followed by stem cell rescue; and twelve 28-day cycles of maintenance therapy with vorinostat and isotretinoin. Patients with M0 medulloblastoma (MB) received focal radiation following consolidation therapy. Molecular classification was by DNA methylation array.
Results
Thirty-one patients with median age of 26 months (range 6-46) received treatment on study; 19 (61%) were male. Diagnosis was MB in 20 and supratentorial CNS embryonal tumor in 11. 24/31 patients completed induction therapy within a pre-specified feasibility window of 98 days. Five-year progression-free survival (PFS) and overall survival (OS) for all 31 patients were 55 ± 15 and 61 ± 13, respectively. Five-year PFS was 42 ± 13 for group 3 MB (n = 12); 80 ± 25 for SHH MB (n = 5); 33 ± 19 for embryonal tumor with multilayered rosettes (ETMR, n = 6).
Conclusion
It was safe and feasible to incorporate vorinostat and isotretinoin into an intensive chemotherapy regimen. Further study to define efficacy in this high-risk group of patients is warranted.</description><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Brain Neoplasms - pathology</subject><subject>Cerebellar Neoplasms - drug therapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cyclophosphamide</subject><subject>Etoposide</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Isotretinoin - therapeutic use</subject><subject>Male</subject><subject>Medulloblastoma - pathology</subject><subject>Neoplasms, Germ Cell and Embryonal - drug therapy</subject><subject>Neuroectodermal Tumors, Primitive - drug therapy</subject><subject>Pediatric Neuro-Oncology</subject><subject>Prospective Studies</subject><subject>Vincristine</subject><subject>Vorinostat</subject><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1OGzEUha2qVQmUbZfIy2Yx4L_5cReVkgjaSpHIImU7up7xEKOMPbI9VHmVPi0OSRGsWN2r4-9-XhyEvlJySYnkV1aPzjZX1oFikn9AE5oznuVVUXx83llW5bQ8QachPBDCaF7Qz-iEC8lzWZQT9O_OeWNdiBAx2Bab4KLXMUXG4r8mbnCz0b2LG-1h2OEU7txo71Nqtq3XR0b3yu-chS1WHhITx9758B3PsNeD8xF33vU4SfBKtwaiNw2eP5PrPYkXzoaEmbHH31bz9SIjrJh-QZ862AZ9fpxn6M_N9XrxK1ve_vy9mC2zRjARM0WYaHRX6QJEpWXHKeW84xxoq1gJVJAKSqFpAyBVqyiXFaGSF0qWVOaJP0M_Dt5hVL1uG22jh209eNOD39UOTP32xZpNfe8ea8lEJQhPgsuDoPEuBK-7l1tK6n1L9aGl-thSOrh4_eML_r-WBEwPgBuH92RP4LKi8g</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Leary, Sarah E S</creator><creator>Kilburn, Lindsay</creator><creator>Geyer, J Russell</creator><creator>Kocak, Mehmet</creator><creator>Huang, Jie</creator><creator>Smith, Kyle S</creator><creator>Hadley, Jennifer</creator><creator>Ermoian, Ralph</creator><creator>MacDonald, Tobey J</creator><creator>Goldman, Stewart</creator><creator>Phillips, Peter</creator><creator>Young Poussaint, Tina</creator><creator>Olson, James M</creator><creator>Ellison, David W</creator><creator>Dunkel, Ira J</creator><creator>Fouladi, Maryam</creator><creator>Onar-Thomas, Arzu</creator><creator>Northcott, Paul A</creator><general>Oxford University Press</general><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>5PM</scope><orcidid>https://orcid.org/0000-0003-0225-6184</orcidid><orcidid>https://orcid.org/0000-0002-5693-035X</orcidid></search><sort><creationdate>20220701</creationdate><title>Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)</title><author>Leary, Sarah E S ; Kilburn, Lindsay ; Geyer, J Russell ; Kocak, Mehmet ; Huang, Jie ; Smith, Kyle S ; Hadley, Jennifer ; Ermoian, Ralph ; MacDonald, Tobey J ; Goldman, Stewart ; Phillips, Peter ; Young Poussaint, Tina ; Olson, James M ; Ellison, David W ; Dunkel, Ira J ; Fouladi, Maryam ; Onar-Thomas, Arzu ; Northcott, Paul A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-b024cef8e6a48e9f31133f33a1db27a1408a74e1caa9bdb139801936b971959f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Brain Neoplasms - pathology</topic><topic>Cerebellar Neoplasms - drug therapy</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cyclophosphamide</topic><topic>Etoposide</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Isotretinoin - therapeutic use</topic><topic>Male</topic><topic>Medulloblastoma - pathology</topic><topic>Neoplasms, Germ Cell and Embryonal - drug therapy</topic><topic>Neuroectodermal Tumors, Primitive - drug therapy</topic><topic>Pediatric Neuro-Oncology</topic><topic>Prospective Studies</topic><topic>Vincristine</topic><topic>Vorinostat</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leary, Sarah E S</creatorcontrib><creatorcontrib>Kilburn, Lindsay</creatorcontrib><creatorcontrib>Geyer, J Russell</creatorcontrib><creatorcontrib>Kocak, Mehmet</creatorcontrib><creatorcontrib>Huang, Jie</creatorcontrib><creatorcontrib>Smith, Kyle S</creatorcontrib><creatorcontrib>Hadley, Jennifer</creatorcontrib><creatorcontrib>Ermoian, Ralph</creatorcontrib><creatorcontrib>MacDonald, Tobey J</creatorcontrib><creatorcontrib>Goldman, Stewart</creatorcontrib><creatorcontrib>Phillips, Peter</creatorcontrib><creatorcontrib>Young Poussaint, Tina</creatorcontrib><creatorcontrib>Olson, James M</creatorcontrib><creatorcontrib>Ellison, David W</creatorcontrib><creatorcontrib>Dunkel, Ira J</creatorcontrib><creatorcontrib>Fouladi, Maryam</creatorcontrib><creatorcontrib>Onar-Thomas, Arzu</creatorcontrib><creatorcontrib>Northcott, Paul A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leary, Sarah E S</au><au>Kilburn, Lindsay</au><au>Geyer, J Russell</au><au>Kocak, Mehmet</au><au>Huang, Jie</au><au>Smith, Kyle S</au><au>Hadley, Jennifer</au><au>Ermoian, Ralph</au><au>MacDonald, Tobey J</au><au>Goldman, Stewart</au><au>Phillips, Peter</au><au>Young Poussaint, Tina</au><au>Olson, James M</au><au>Ellison, David W</au><au>Dunkel, Ira J</au><au>Fouladi, Maryam</au><au>Onar-Thomas, Arzu</au><au>Northcott, Paul A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><addtitle>Neuro Oncol</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>24</volume><issue>7</issue><spage>1178</spage><epage>1190</epage><pages>1178-1190</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract
Background
Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone.
Methods
PBTC-026 was a prospective multi-institutional clinical trial for children <48 months of age with newly diagnosed embryonal tumors of the CNS. Treatment included three 21-day cycles of induction therapy with vorinostat and isotretinoin, cisplatin, vincristine, cyclophosphamide, and etoposide; three 28-day cycles of consolidation therapy with carboplatin and thiotepa followed by stem cell rescue; and twelve 28-day cycles of maintenance therapy with vorinostat and isotretinoin. Patients with M0 medulloblastoma (MB) received focal radiation following consolidation therapy. Molecular classification was by DNA methylation array.
Results
Thirty-one patients with median age of 26 months (range 6-46) received treatment on study; 19 (61%) were male. Diagnosis was MB in 20 and supratentorial CNS embryonal tumor in 11. 24/31 patients completed induction therapy within a pre-specified feasibility window of 98 days. Five-year progression-free survival (PFS) and overall survival (OS) for all 31 patients were 55 ± 15 and 61 ± 13, respectively. Five-year PFS was 42 ± 13 for group 3 MB (n = 12); 80 ± 25 for SHH MB (n = 5); 33 ± 19 for embryonal tumor with multilayered rosettes (ETMR, n = 6).
Conclusion
It was safe and feasible to incorporate vorinostat and isotretinoin into an intensive chemotherapy regimen. Further study to define efficacy in this high-risk group of patients is warranted.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>34935967</pmid><doi>10.1093/neuonc/noab293</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-0225-6184</orcidid><orcidid>https://orcid.org/0000-0002-5693-035X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Antineoplastic Combined Chemotherapy Protocols - therapeutic use Brain Neoplasms - pathology Cerebellar Neoplasms - drug therapy Child Child, Preschool Cyclophosphamide Etoposide Female Humans Infant Isotretinoin - therapeutic use Male Medulloblastoma - pathology Neoplasms, Germ Cell and Embryonal - drug therapy Neuroectodermal Tumors, Primitive - drug therapy Pediatric Neuro-Oncology Prospective Studies Vincristine Vorinostat |
| title | Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026) |
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