mefloquine + memantine + metformin + temozolomide

This is a combination regimen consisting of four small-molecule drugs—mefloquine, memantine, metformin, and temozolomide—investigated primarily for the treatment of newly diagnosed glioblastoma. Each component has a distinct mechanism of action: - **Mefloquine** is an antimalarial agent that disrupts parasite membrane function and has been repurposed for its potential anticancer effects. - **Memantine** is an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, used in Alzheimer's disease and investigated here for its neuroprotective and possible anticancer properties. - **Metformin** is a biguanide antihyperglycemic agent commonly used in type 2 diabetes; it inhibits mitochondrial respiratory chain complex I, affecting cellular metabolism with putative anticancer activity. - **Temozolomide** is an oral alkylating chemotherapy agent that methylates DNA at the O6 and N7 positions of guanine, leading to tumor cell death. Clinical studies have shown that this quadruple combination can be administered safely at defined maximum tolerated doses in patients with newly diagnosed glioblastoma. The most common adverse events include lymphopenia (66%) and fatigue (65%), with dose-limiting toxicities such as dizziness (memantine) and gastrointestinal effects (metformin). This regimen represents a novel approach by combining agents with different mechanisms to target both tumor cells directly and their metabolic environment[1][6][10].

Other names

metformin-M.D. Anderson Cancer Center-glioblastoma multiforme-gliosarcomaTemozolomide, Memantine, Mefloquine, and Metformin combination therapyNCT02780024 regimenNCT-02780024 regimenNCT 02780024 regimen