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
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- Stefania Maraka
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Morris D. Groves
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Aaron G. Mammoser
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Isaac Melguizo‐Gavilanes
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Charles A. Conrad
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Ivo W. Tremont‐Lukats
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Monica E. Loghin
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Barbara J. O’Brien
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Vinay K. Puduvalli
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Erik P. Sulman
- Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Kenneth R. Hess
- Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas
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- Kenneth D. Aldape
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Mark R. Gilbert
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- John F. de Groot
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- W.K. Alfred Yung
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
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- Marta Penas‐Prado
- Department of Neuro‐Oncology The University of Texas MD Anderson Cancer Center Houston Texas
Description
<jats:sec><jats:title>Background</jats:title><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></jats:sec><jats:sec><jats:title>Methods</jats:title><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‐limiting toxicities (DLTs) were determined, using a 3 + 3 study design.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><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‐year survival rate was 43%.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.</jats:p></jats:sec>
Journal
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- Cancer
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Cancer 125 (3), 424-433, 2018-10-25
Wiley
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Details 詳細情報について
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- CRID
- 1360017289889534208
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- ISSN
- 10970142
- 0008543X
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- Data Source
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- Crossref