A phase II trial of oral gimatecan for recurrent glioblastoma
Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, Eas...
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| Veröffentlicht in: | Journal of neuro-oncology 2013-02, Vol.111 (3), p.347-353 |
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| creator | Hu, Jethro Wen, Patrick Y. Abrey, Lauren E. Fadul, Camilo E. Drappatz, Jan Salem, Nadia Supko, Jeffrey G. Hochberg, Fred |
| description | Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, Eastern Cooperative Oncology Group performance status 0–1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m
2
was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if
>
4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m
2
after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m
2
/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m
2
/day for 5 days, repeated every 28-days showed minimal efficacy. |
| doi_str_mv | 10.1007/s11060-012-1023-0 |
| format | Article |
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2
was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if
>
4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m
2
after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m
2
/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m
2
/day for 5 days, repeated every 28-days showed minimal efficacy.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-012-1023-0</identifier><identifier>PMID: 23232808</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Administration, Oral ; Adult ; Age ; Aged ; Antineoplastic Agents, Phytogenic - therapeutic use ; Brain Neoplasms - drug therapy ; Brain tumors ; Camptothecin ; Camptothecin - analogs & derivatives ; Camptothecin - therapeutic use ; Chemotherapy ; Clinical Study ; Clinical trials ; Disease-Free Survival ; Female ; Glioblastoma ; Glioblastoma - drug therapy ; Glioma ; Humans ; Kaplan-Meier Estimate ; Leukopenia ; Lipophilic ; Magnetic Resonance Imaging ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Recurrence, Local - drug therapy ; Neurology ; Neutropenia ; Oncology ; Radiation ; Retrospective Studies ; Surgery ; Survival ; Thrombocytopenia ; Toxicity ; Treatment Outcome</subject><ispartof>Journal of neuro-oncology, 2013-02, Vol.111 (3), p.347-353</ispartof><rights>Springer Science+Business Media New York 2012</rights><rights>Springer Science+Business Media New York 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-f7e994202bbf6ab721d4bcfdece32b4fca248f4471c4ce87fdd4d3bf4dd367003</citedby><cites>FETCH-LOGICAL-c405t-f7e994202bbf6ab721d4bcfdece32b4fca248f4471c4ce87fdd4d3bf4dd367003</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/s11060-012-1023-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11060-012-1023-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27926,27927,41490,42559,51321</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23232808$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Jethro</creatorcontrib><creatorcontrib>Wen, Patrick Y.</creatorcontrib><creatorcontrib>Abrey, Lauren E.</creatorcontrib><creatorcontrib>Fadul, Camilo E.</creatorcontrib><creatorcontrib>Drappatz, Jan</creatorcontrib><creatorcontrib>Salem, Nadia</creatorcontrib><creatorcontrib>Supko, Jeffrey G.</creatorcontrib><creatorcontrib>Hochberg, Fred</creatorcontrib><title>A phase II trial of oral gimatecan for recurrent glioblastoma</title><title>Journal of neuro-oncology</title><addtitle>J Neurooncol</addtitle><addtitle>J Neurooncol</addtitle><description>Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, Eastern Cooperative Oncology Group performance status 0–1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m
2
was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if
>
4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m
2
after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m
2
/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m
2
/day for 5 days, repeated every 28-days showed minimal efficacy.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Antineoplastic Agents, Phytogenic - therapeutic use</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain tumors</subject><subject>Camptothecin</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - therapeutic use</subject><subject>Chemotherapy</subject><subject>Clinical Study</subject><subject>Clinical trials</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Glioblastoma</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioma</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukopenia</subject><subject>Lipophilic</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neurology</subject><subject>Neutropenia</subject><subject>Oncology</subject><subject>Radiation</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Survival</subject><subject>Thrombocytopenia</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><issn>0167-594X</issn><issn>1573-7373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkU1LxDAQhoMo7rr6A7xIwIuX6uSjTXvwsCx-LCx4UfAW0jRZu3SbNWkP_ntTuooIgsxhDvPMOx8vQucErgmAuAmEQAYJEJoQoCyBAzQlqWCJYIIdoimQTCRpwV8n6CSEDQBwwcgxmlAWI4d8im7nePemgsHLJe58rRrsLHY-5nW9VZ3RqsXWeeyN7r03bYfXTe3KRoXObdUpOrKqCeZsn2fo5f7uefGYrJ4elov5KtEc0i6xwhQFp0DL0maqFJRUvNS2MtowWnKrFeW55VwQzbXJha0qXrHS8qpimQBgM3Q16u68e-9N6OS2Dto0jWqN64MktCAZ5KxI_4HmKYiioHlEL3-hG9f7Nh4yUJxmOc14pMhIae9C8MbKnY-v8R-SgBxskKMNMtogBxvksO_FXrkvt6b67vj6ewToCIRYatfG_xj9p-on9GuQzg</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Hu, Jethro</creator><creator>Wen, Patrick Y.</creator><creator>Abrey, Lauren E.</creator><creator>Fadul, Camilo E.</creator><creator>Drappatz, Jan</creator><creator>Salem, Nadia</creator><creator>Supko, Jeffrey G.</creator><creator>Hochberg, Fred</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7TK</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>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>A phase II trial of oral gimatecan for recurrent glioblastoma</title><author>Hu, Jethro ; Wen, Patrick Y. ; Abrey, Lauren E. ; Fadul, Camilo E. ; Drappatz, Jan ; Salem, Nadia ; Supko, Jeffrey G. ; Hochberg, Fred</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-f7e994202bbf6ab721d4bcfdece32b4fca248f4471c4ce87fdd4d3bf4dd367003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Antineoplastic Agents, Phytogenic - therapeutic use</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain tumors</topic><topic>Camptothecin</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - therapeutic use</topic><topic>Chemotherapy</topic><topic>Clinical Study</topic><topic>Clinical trials</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Glioblastoma</topic><topic>Glioblastoma - drug therapy</topic><topic>Glioma</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukopenia</topic><topic>Lipophilic</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neurology</topic><topic>Neutropenia</topic><topic>Oncology</topic><topic>Radiation</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Survival</topic><topic>Thrombocytopenia</topic><topic>Toxicity</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Jethro</creatorcontrib><creatorcontrib>Wen, Patrick Y.</creatorcontrib><creatorcontrib>Abrey, Lauren E.</creatorcontrib><creatorcontrib>Fadul, Camilo E.</creatorcontrib><creatorcontrib>Drappatz, Jan</creatorcontrib><creatorcontrib>Salem, Nadia</creatorcontrib><creatorcontrib>Supko, Jeffrey G.</creatorcontrib><creatorcontrib>Hochberg, Fred</creatorcontrib><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>Neurosciences 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>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>MEDLINE - Academic</collection><jtitle>Journal of neuro-oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Jethro</au><au>Wen, Patrick Y.</au><au>Abrey, Lauren E.</au><au>Fadul, Camilo E.</au><au>Drappatz, Jan</au><au>Salem, Nadia</au><au>Supko, Jeffrey G.</au><au>Hochberg, Fred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A phase II trial of oral gimatecan for recurrent glioblastoma</atitle><jtitle>Journal of neuro-oncology</jtitle><stitle>J Neurooncol</stitle><addtitle>J Neurooncol</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>111</volume><issue>3</issue><spage>347</spage><epage>353</epage><pages>347-353</pages><issn>0167-594X</issn><eissn>1573-7373</eissn><abstract>Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, Eastern Cooperative Oncology Group performance status 0–1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m
2
was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if
>
4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m
2
after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m
2
/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m
2
/day for 5 days, repeated every 28-days showed minimal efficacy.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23232808</pmid><doi>10.1007/s11060-012-1023-0</doi><tpages>7</tpages></addata></record> |
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| subjects | Administration, Oral Adult Age Aged Antineoplastic Agents, Phytogenic - therapeutic use Brain Neoplasms - drug therapy Brain tumors Camptothecin Camptothecin - analogs & derivatives Camptothecin - therapeutic use Chemotherapy Clinical Study Clinical trials Disease-Free Survival Female Glioblastoma Glioblastoma - drug therapy Glioma Humans Kaplan-Meier Estimate Leukopenia Lipophilic Magnetic Resonance Imaging Male Medicine Medicine & Public Health Middle Aged Neoplasm Recurrence, Local - drug therapy Neurology Neutropenia Oncology Radiation Retrospective Studies Surgery Survival Thrombocytopenia Toxicity Treatment Outcome |
| title | A phase II trial of oral gimatecan for recurrent glioblastoma |
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