{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:24:56Z","timestamp":1790717096065,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T00:00:00Z","timestamp":1384819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>mTOR inhibitors have activity in pediatric tumor models. A phase I trial of the mTOR inhibitor temsirolimus (TEM) with irinotecan (IRN) and temozolomide (TMZ) was conducted in children with recurrent\/refractory solid tumors, including central nervous system (CNS) tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Escalating doses of intravenous (IV) TEM were administered on days 1 and 8 of 21\u2010day cycles. IRN (50\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose escalated to a maximum of 90\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose) and TMZ (100\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose escalated to a maximum of 150\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose) were administered orally (PO) on days 1\u20135. When maximum tolerated doses (MTD) were identified, TEM frequency was increased to weekly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy\u2010one eligible pts (median age 10.9 years, range 1.0\u201321.5) with neuroblastoma (16), osteosarcoma (7), Ewing sarcoma (7), rhabdomyosarcoma (4), CNS (22) or other (15) tumors were enrolled. Dose\u2010limiting hyperlipidemia occurred in two patients receiving oral corticosteroids. The protocol was subsequently amended to preclude chronic steroid use. The MTD was identified as TEM 35\u2009mg\/m<jats:sup>2<\/jats:sup> IV weekly, with IRN 90\u2009mg\/m<jats:sup>2<\/jats:sup> and TMZ 125\u2009mg\/m<jats:sup>2<\/jats:sup> PO on days 1\u20135. At higher dose levels, elevated serum alanine aminotransferase and triglycerides, anorexia, and thrombocytopenia were dose limiting. Additional \u2265grade 3 regimen\u2010related toxicities included leukopenia, neutropenia, lymphopenia, anemia, and nausea\/vomiting. Six patients had objective responses confirmed by central review; three of these had sustained responses through \u226514 cycles of therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of TEM (35\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose IV weekly), IRN (90\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose days 1\u20135) and TMZ (125\u2009mg\/m<jats:sup>2<\/jats:sup>\/dose days 1\u20135) administered PO every 21 days is well tolerated in children. Phase 2 trials of this combination are ongoing. Pediatr Blood Cancer 2014;61:833\u2013839. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.24874","type":"journal-article","created":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T11:51:46Z","timestamp":1384861906000},"page":"833-839","source":"Crossref","is-referenced-by-count":88,"title":["Phase 1 trial of temsirolimus in combination with irinotecan and temozolomide in children, adolescents and young adults with relapsed or refractory solid tumors: A children's oncology group study"],"prefix":"10.1002","volume":"61","author":[{"given":"Rochelle","family":"Bagatell","sequence":"first","affiliation":[{"name":"The Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Norris","sequence":"additional","affiliation":[{"name":"Rainbow Babies and Children's Hospital Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish 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Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda J.","family":"Weigel","sequence":"additional","affiliation":[{"name":"University of Minnesota Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Adamson","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Blaney","sequence":"additional","affiliation":[{"name":"Texas Children's Cancer Center\/Baylor College of Medicine Houston 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