{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:24:52Z","timestamp":1790238292121,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T00:00:00Z","timestamp":1475193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NCI Cancer Center Support Grant","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]},{"name":"Gerber Foundation, Fremont, MI; the Robert Steel Foundation, New York, NY; Katie's Find A Cure Fund, New York, NY"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"<jats:p>AKT plays a pivotal role in driving the malignant phenotype of many cancers, including high\u2010risk neuroblastoma (HR\u2010NB). AKT signaling, however, is active in normal tissues, raising concern about excessive toxicity from its suppression. The oral AKT inhibitor perifosine showed tolerable toxicity in adults and in our phase I trial in children with solid tumors (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link> NCT00776867). We now report on the HR\u2010NB experience. HR\u2010NB patients received perifosine 50\u201375 mg\u00a0m<jats:sup>\u22122<\/jats:sup>\u00a0day<jats:sup>\u22121<\/jats:sup> after a loading dose of 100\u2013200 mg\u00a0m<jats:sup>\u22122<\/jats:sup> on day 1, and continued on study until progressive disease. The 27 HR\u2010NB patients included three treated for primary refractory disease and 24 with disease resistant to salvage therapy after 1\u20135 (median 2) relapses; only one had <jats:italic>MYCN<\/jats:italic>\u2010amplified HR\u2010NB. Pharmacokinetic studies showed \u03bcM concentrations consistent with cytotoxic levels in preclinical models. Nine patients (all <jats:italic>MYCN<\/jats:italic>\u2010non\u2010amplified) remained progression\u2010free through 43+ to 74+ (median 54+) months from study entry, including the sole patient to show a complete response and eight patients who had persistence of abnormal <jats:sup>123<\/jats:sup>I\u2010metaiodobenzylguanidine skeletal uptake but never developed progressive disease. Toxicity was negligible in all 27 patients, even with the prolonged treatment (11\u201362 months, median 38) in the nine long\u2010term progression\u2010free survivors. The clinical findings (<jats:italic>i<\/jats:italic>) confirm the safety of therapeutic serum levels of an AKT inhibitor in children; (<jats:italic>ii<\/jats:italic>) support perifosine for <jats:italic>MYCN<\/jats:italic>\u2010non\u2010amplified HR\u2010NB as monotherapy after completion of standard treatment or combined with other agents (based on preclinical studies) to maximize antitumor effects; and (<jats:italic>iii<\/jats:italic>) highlight the welcome possibility that refractory or relapsed <jats:italic>MYCN<\/jats:italic>\u2010non\u2010amplified HR\u2010NB is potentially curable.<\/jats:p>","DOI":"10.1002\/ijc.30440","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T00:02:52Z","timestamp":1474416172000},"page":"480-484","source":"Crossref","is-referenced-by-count":48,"title":["A phase I\/Ib trial targeting the Pi3k\/Akt pathway using perifosine: <scp>L<\/scp>ong\u2010term progression\u2010free survival of patients with resistant neuroblastoma"],"prefix":"10.1002","volume":"140","author":[{"given":"Brian H.","family":"Kushner","sequence":"first","affiliation":[{"name":"Department of Pediatrics Memorial Sloan Kettering Cancer Center New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai\u2010Kong V.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Memorial Sloan Kettering Cancer Center New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakeel","family":"Modak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Memorial Sloan Kettering Cancer Center New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren J.","family":"Becher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen 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