dimethyl fumarate + temozolomide

Dimethyl fumarate + temozolomide is an investigational combination therapy evaluated primarily in the treatment of glioblastoma (GBM). Dimethyl fumarate (DMF) is an oral small molecule approved for relapsing-remitting multiple sclerosis and psoriasis, with mechanisms involving activation of the Nrf2 pathway, inhibition of NF-κB, and broad antioxidant, immunomodulatory, neuroprotective, anti-inflammatory, and anti-proliferative effects. Temozolomide (TMZ) is a DNA-alkylating agent used as standard chemotherapy for GBM; it induces cytotoxicity by methylating DNA at guanine residues leading to tumor cell death. Preclinical data suggest synergism between DMF and TMZ when combined with radiotherapy. In phase I clinical trials in newly diagnosed GBM patients receiving concurrent radiotherapy and TMZ followed by maintenance TMZ plus DMF, the combination was found to be safe without unexpected toxicities[1][3]. The most common severe adverse events were lymphopenia and thrombocytopenia. The recommended phase 2 dose for DMF in this setting was established as 240 mg three times daily[1].