Temozolomide — Drug Monograph

Brand names: Temodar

Drug class: Alkylating Agent

Mechanism of Action

Oral imidazotetrazine prodrug spontaneously converted to MTIC (methyltriazen-1-yl-imidazole-4-carboxamide) at physiological pH. MTIC alkylates guanine at O6 position, causing DNA damage and apoptosis. O6-methylguanine-DNA methyltransferase (MGMT) is the primary resistance mechanism — MGMT promoter methylation silences the gene, predicting benefit from temozolomide in glioblastoma.

FDA Indications

• Newly diagnosed glioblastoma multiforme (GBM) — concomitant with and following radiotherapy (Stupp protocol)
• Refractory anaplastic astrocytoma

Common Side Effects

• Nausea and vomiting (moderate emetic risk)
• Fatigue
• Constipation
• Headache
• Lymphopenia (universal with concurrent radiation)
• Alopecia (partial)
• Anorexia

Clinical Pearl

MGMT promoter methylation status is the most important predictive biomarker for GBM patients — methylation predicts ~50–60% response rate vs. ~25% for unmethylated. Elderly patients (>70) with unmethylated MGMT may receive temozolomide monotherapy rather than the Stupp protocol based on quality-of-life considerations. In pancreatic NETs (pNETs), temozolomide is the backbone of the CAPTEM regimen (capecitabine 750 mg/m² BID days 1–14 + temozolomide 150–200 mg/m² days 10–14 every 28 days) — MGMT…

Related Therapies & Mechanisms

• CAPTEM Regimen (Capecitabine + Temozolomide) (Xeloda + Temodar) — Alkylating Agent · NET
• Carmustine (BiCNU) — Alkylating Agent · GBM
• Dacarbazine (DTIC-Dome) — Alkylating Agent · Melanoma
• Lomustine (Gleostine) — Alkylating Agent · GBM