temozolomid

Temozolomide, also spelled temozolomid in some regions, is an oral alkylating chemotherapy agent used primarily in the treatment of certain brain tumors. It is a prodrug of the active methylating compound MTIC and can cross the blood–brain barrier, allowing it to reach tumor cells within the central nervous system.

Mechanism of action and pharmacology

Temozolomide undergoes spontaneous conversion to MTIC after administration, which methylates DNA at the O6 and N7 positions of guanine. This DNA damage triggers tumor cell death. The extent of response is influenced by the activity of the MGMT repair enzyme; tumors with a methylated MGMT promoter (reduced MGMT expression) tend to respond better.

Medical uses

Temozolomide is approved for adults with glioblastoma multiforme and other high-grade gliomas, including anaplastic astrocytoma. It is a key component of the Stupp protocol for newly diagnosed glioblastoma, in which temozolomide is given with radiotherapy and followed by adjuvant temozolomide cycles. It is also employed in recurrent high-grade gliomas and in some cases of other CNS tumors, depending on regional guidelines and physician judgment.

Administration and pharmacokinetics

Temozolomide is taken orally and has good bioavailability. It is rapidly absorbed and converted to MTIC; the drug and its metabolites are cleared mainly by the liver and kidneys. It crosses the blood–brain barrier effectively, enabling CNS tumor activity. The elimination half-life is relatively short, requiring repeated dosing in cycles typically organized in a monthly schedule.

Adverse effects and considerations

Common adverse effects include hematologic toxicity (neutropenia, thrombocytopenia), fatigue, nausea, vomiting, constipation, and liver enzyme elevations. Mucositis, alopecia, and headaches may occur. Rare serious effects include interstitial pneumonitis and secondary malignancies. Temozolomide is used with caution in pregnancy and in patients with significant hepatic impairment; drug interactions and cumulative marrow suppression are considerations during treatment.

Research and outlook

Ongoing studies explore combination regimens, biomarkers such as MGMT status to guide therapy, and use in recurrent or refractory CNS tumors, as well as expanding indications and optimizing dosing strategies.