Temozolomide

Temozolomide is an oral alkylating agent used primarily in the treatment of malignant gliomas, notably glioblastoma multiforme and anaplastic astrocytoma. It is a prodrug that rapidly hydrolyzes at physiological pH to the active methylating species MTIC, and it crosses the blood-brain barrier, enabling activity in brain tumors. Brand name Temodar.

Mechanism of action and pharmacology: MTIC methylates DNA at O6-guanine and other sites, triggering cytotoxic DNA damage in tumor cells. DNA repair by the O6-methylguanine-DNA methyltransferase (MGMT) enzyme can mitigate the effect; tumors with silenced MGMT due to promoter methylation tend to respond better to therapy.

Indications and regimens: Temozolomide is used for malignant gliomas, including newly diagnosed and recurrent glioblastoma multiforme and anaplastic astrocytoma, often in combination with radiotherapy (the Stupp protocol) followed by adjuvant temozolomide. Dosing is typically 150–200 mg/m2 per day for 5 days in a 28-day cycle, adjusted for hematologic toxicity. The capsules are taken orally, without regard to meals.

Safety and monitoring: Common adverse effects include nausea, vomiting, fatigue, constipation, and headache; hematologic toxicity (neutropenia, thrombocytopenia) is dose-limiting and requires frequent blood count monitoring. Other possible effects include liver enzyme elevations, alopecia, dermatitis, and rare secondary malignancies. Caution in pregnancy; concomitant radiotherapy or other myelosuppressive therapies can increase toxicity.

Additional notes: Temozolomide is generally well tolerated and is a standard component of therapy for glioblastoma. It is marketed as Temodar and manufactured by Merck. Its effectiveness correlates with MGMT promoter methylation status, and MGMT testing is sometimes used to guide prognosis and treatment decisions.