## Standard Adjuvant Chemotherapy for Glioblastoma **Key Point:** Temozolomide is the gold-standard alkylating agent for WHO Grade IV glioblastoma, used as both concurrent and adjuvant therapy following surgery and radiotherapy. **High-Yield:** The landmark Stupp protocol (2005) established concurrent temozolomide during radiotherapy followed by 6 cycles of adjuvant temozolomide as the standard of care for newly diagnosed glioblastoma. This regimen significantly improves overall survival compared to radiotherapy alone. ### Why Temozolomide? | Feature | Temozolomide | Cisplatin | Methotrexate | Vincristine | |---------|--------------|-----------|--------------|-------------| | **BBB penetration** | Excellent (lipophilic) | Poor | Poor | Poor | | **Oral bioavailability** | Yes | No (IV only) | No (IV/IT) | No (IV only) | | **Standard glioblastoma use** | Yes (Stupp protocol) | No | No | No (used in pediatric medulloblastoma) | | **Myelosuppression** | Moderate | Severe | Moderate | Severe | | **Renal toxicity** | Minimal | Significant | Minimal | Minimal | **Clinical Pearl:** Temozolomide undergoes spontaneous hydrolysis at physiologic pH to form the active metabolite MTIC (methyltriazenimidazole carboxamide), which methylates DNA at the O-6 position of guanine, leading to apoptosis. Its lipophilic nature allows superior blood–brain barrier (BBB) penetration compared to hydrophilic agents. **Mnemonic:** **STUPP** = Surgery, Temozolomide (concurrent), Radiotherapy, Post-operative temozolomide (adjuvant) — the standard protocol for glioblastoma. ### Dosing in Glioblastoma 1. **Concurrent phase:** 75 mg/m² daily during radiotherapy (6 weeks) 2. **Adjuvant phase:** 150–200 mg/m² daily for 5 days, repeated every 28 days for up to 6 cycles **Warning:** Patients with methylated MGMT (O-6-methylguanine-DNA methyltransferase) promoter show better response to temozolomide and improved prognosis — MGMT status is now a key prognostic and predictive marker in glioblastoma. [cite:Robbins 10e Ch 28]
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