## Drug of Choice for Glioblastoma Adjuvant Chemotherapy **Key Point:** Temozolomide (TMZ) is the gold-standard alkylating agent for glioblastoma, both during concurrent chemoradiation and in the adjuvant setting, particularly in MGMT-methylated tumors. ### Mechanism and Evidence Temozolomide is an oral alkylating agent that crosses the blood–brain barrier and causes DNA methylation. The landmark **Stupp protocol** (2005, updated 2009) demonstrated that concurrent TMZ with radiotherapy followed by 6 cycles of adjuvant TMZ significantly improved overall survival (14.6 months vs 12.1 months with radiation alone) in newly diagnosed glioblastoma. ### MGMT Methylation Status In this case, the tumor is **MGMT-methylated**, which is a strong predictor of TMZ responsiveness: - MGMT methylation silences the DNA repair enzyme O^6^-methylguanine-DNA methyltransferase - Methylated tumors show superior response to alkylating agents - This patient is an ideal candidate for TMZ-based therapy ### Standard Dosing and Schedule | Parameter | Detail | |-----------|--------| | **Concurrent phase** | 75 mg/m² daily (days 1–42 of radiotherapy) | | **Adjuvant phase** | 150–200 mg/m² daily × 5 days, repeated every 28 days for 6 cycles | | **Route** | Oral | | **Key advantage** | Good CNS penetration, oral bioavailability, tolerable toxicity profile | **High-Yield:** MGMT methylation status is the single most important prognostic and predictive marker in glioblastoma — methylated tumors have longer survival with TMZ. **Clinical Pearl:** Temozolomide-related myelosuppression requires baseline and regular CBC monitoring; prophylactic PCP prophylaxis (trimethoprim-sulfamethoxazole) is standard during adjuvant cycles. [cite:Stupp et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM 2005; Harrison 21e Ch 397]
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