{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:03:06Z","timestamp":1792782186996,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Departmental funds"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Repurposed memantine, mefloquine, and metformin have putative anticancer activity. The objective of this phase 1 study was to determine the maximum tolerated doses (MTDs) of combinations of these agents with temozolomide (TMZ).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adults with newly diagnosed glioblastoma who completed chemoradiation were eligible. The patients were assigned to receive doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and\/or metformin. Dose\u2010limiting toxicities (DLTs) were determined, using a 3 + 3 study design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 85 enrolled patients, 4 did not complete cycle 1 (the DLT observation period) for nontoxicity reasons, and 81 were evaluable for DLT. The MTDs for doublet therapy were memantine 20 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For triplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For quadruplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 500 mg twice daily. DLTs included dizziness (memantine) and gastrointestinal effects (metformin). Lymphopenia was the most common adverse event (66%). From study entry, the median survival was 21 months, and the 2\u2010year survival rate was 43%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.31811","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T17:54:47Z","timestamp":1540490087000},"page":"424-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Phase 1 lead\u2010in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-3320","authenticated-orcid":false,"given":"Stefania","family":"Maraka","sequence":"first","affiliation":[{"name":"Department of Neuro\u2010Oncology The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris D.","family":"Groves","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron G.","family":"Mammoser","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Melguizo\u2010Gavilanes","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology The 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