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Phase 1 lead-in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma.
- Source :
-
Cancer (0008543X) . Feb2019, Vol. 125 Issue 3, p424-433. 10p. - Publication Year :
- 2019
-
Abstract
- <bold>Background: </bold>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).<bold>Methods: </bold>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-limiting toxicities (DLTs) were determined, using a 3 + 3 study design.<bold>Results: </bold>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-year survival rate was 43%.<bold>Conclusions: </bold>Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TEMOZOLOMIDE
*GLIOBLASTOMA multiforme
*METFORMIN
*MEMANTINE
*GLIOMAS
Subjects
Details
- Language :
- English
- ISSN :
- 0008543X
- Volume :
- 125
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cancer (0008543X)
- Publication Type :
- Academic Journal
- Accession number :
- 134232587
- Full Text :
- https://doi.org/10.1002/cncr.31811