{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:34:25Z","timestamp":1784291665643,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T00:00:00Z","timestamp":1438300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC) (Cortice Biosciences)"},{"name":"Beat NB Foundation"},{"name":"Max's Ring of Fire"},{"name":"Meryl and Charles Witmer Foundation"},{"name":"Owen Moscone Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28\u2010day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters C<jats:sub>max<\/jats:sub>, AUC<jats:sub>0\u201024<\/jats:sub>, t<jats:sub>1\/2<\/jats:sub>, CL, and V<jats:sub>d<\/jats:sub> on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287\u2009+\u2009TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125\u2009mg\/m<jats:sup>2<\/jats:sup>. The non\u2010dose\u2010limiting toxicities at this dose were mainly anorexia and pain. The dose\u2010limiting toxicities (DLTs) of two patients at 135\u2009mg\/m<jats:sup>2<\/jats:sup> were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125\u2009mg\/m<jats:sup>2<\/jats:sup> IV on days 1, 8, and 15 of a 28 day cycle. Pediatr Blood Cancer 2015; 9999:1\u20138 \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.25687","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T16:08:52Z","timestamp":1438358932000},"page":"39-46","source":"Crossref","is-referenced-by-count":28,"title":["A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma"],"prefix":"10.1002","volume":"63","author":[{"given":"Deanna","family":"Mitchell","sequence":"first","affiliation":[{"name":"Helen DeVos Children's Hospital Grand Rapids Michigan"},{"name":"Michigan State University College of Human Medicine Grand Rapids Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Bergendahl","sequence":"additional","affiliation":[{"name":"Helen DeVos Children's Hospital Grand Rapids Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Cardinal Glennon Children's Medical Center Saint Louis University School of Medicine Saint Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Roberts","sequence":"additional","affiliation":[{"name":"Rady Children's Hospital University of California San Diego School of Medicine San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Vermont Medical Center Burlington Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamaru","family":"Ashikaga","sequence":"additional","affiliation":[{"name":"Medical Biostatistics and Biometry Facility University of Vermont College of Medicine Burlington Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"DeSarno","sequence":"additional","affiliation":[{"name":"Medical Biostatistics and Biometry Facility University of Vermont College of Medicine Burlington Vermont"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Levine Children's Hospital Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Kraveka","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Charleston South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Eslin","sequence":"additional","affiliation":[{"name":"Arnold Palmer Hospital for Children Orlando Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa Vander","family":"Werff","sequence":"additional","affiliation":[{"name":"Helen DeVos Children's Hospital Grand Rapids Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina K.","family":"Hanna","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle L. Saulnier","family":"Sholler","sequence":"additional","affiliation":[{"name":"Helen DeVos Children's Hospital Grand Rapids Michigan"},{"name":"Michigan State University College of Human Medicine Grand Rapids Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,31]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Society AC.Cancer facts and figures. Atlanta GA: American Cancer Society;2008."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1992.10.2.323"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.8.1466"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2007.10.014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1701737"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910143411601"},{"key":"e_1_2_7_8_1","unstructured":"(CBTRUS) CBTRotUS. 2007\u20132008 Primary Brain Tumors of the United States. 2008:2000\u20132004 (Years Data Collected)."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e3282f0eafa"},{"key":"e_1_2_7_10_1","first-page":"1769","article-title":"Activity of temozolomide against human tumor colony\u2010forming units","volume":"3","author":"Raymond E","year":"1997","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_11_1","first-page":"998","article-title":"Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models","volume":"6","author":"Middlemas DS","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_12_1","first-page":"116\u2010b\u2010117","article-title":"Oral bioavailabity and antitumor activity of TPI 287 a new taxane analog with greater activity than paclitaxel against tumor cells with demonstrated mutant tubulin","volume":"2006","author":"Emerson DL","year":"2006","journal-title":"AACR Meeting Abstracts"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0061"},{"key":"e_1_2_7_14_1","first-page":"1441","article-title":"TPI 287 crosses the blood brain barrier and contributes to antitumor activity in the U251 glioblastoma intracranial tumor model in nude mice","author":"Emerson D","year":"2007","journal-title":"AACR Meeting Abstracts"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4281"},{"key":"e_1_2_7_16_1","first-page":"13510","article-title":"A phase I study of TPI 287, a novel taxane, administered every 21 days in patients (pts) with advanced cancer","volume":"26","author":"Modiano MR","year":"2008","journal-title":"ASCO Meeting Abstracts"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.555"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.9.3037"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.03.023"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1016"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0305-7372(97)90019-0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.1572"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.6785"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00173682"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2005.12.010"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1548-5315(11)70224-8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00171-X"},{"key":"e_1_2_7_28_1","first-page":"439","volume-title":"Handbook of food, drug, and cosmetic excipients","author":"Smolinske SC","year":"1992"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.curtheres.2014.09.002"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2624"},{"key":"e_1_2_7_31_1","first-page":"TPS329","article-title":"A phase I trial of TPI\u2010287 as a single agent and its combination with temozolomide in relapsed neuroblastoma or medulloblastoma","volume":"28","author":"Saulnier Sholler GL","year":"2010","journal-title":"ASCO Meeting Abstracts"},{"key":"e_1_2_7_32_1","first-page":"9554","article-title":"Phase I trial of TPI 287 as a single agent and in combination with temozolomide (TMZ) in patients with refractory or recurrent neuroblastoma (NB) or medulloblastoma (MB)","volume":"29","author":"Saulnier Sholler GL","year":"2011","journal-title":"ASCO Meeting Abstracts"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.25687","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.25687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T20:29:37Z","timestamp":1695760177000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.25687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,31]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1002\/pbc.25687"],"URL":"https:\/\/doi.org\/10.1002\/pbc.25687","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,31]]}}}