Temozolomide (Temodar)

Last updated 4/26/25

What It Is

Temozolomide (TMZ) is an oral alkylating agent that crosses the blood-brain barrier. In the stomach it converts to MTIC, which methylates DNA at the O₆- and N₇-guanine positions, causing tumor-cell death.

Names & Formulations (USA)

• Brand: Temodar® (Merck & Co.) - 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg capsules, plus 100 mg IV powder.
• Generics: FDA-approved equivalents from Dr Reddy's, Teva, Mylan, Amneal, Zydus, etc.
• Device combo: Optune used together with oral Temodar (the device has a separate FDA PMA).

How It Is Used

All doses are based on body-surface area (BSA). You can calculate BSA and the exact Temozolomide dose with our online calculator: BSA & Dose Calculator.

Setting	Typical Schedule	Key Points
Concomitant with radiation	75 mg/m2 daily x 42 days	Hold if ANC < 1.5 K or PLT < 100 K; give TMP-SMX prophylaxis.
Maintenance/adjuvant	150 mg/m2 to 200 mg/m2 daily on Days 1-5 every 28 days (minimum 6 cycles)	Many centers extend to 12 cycles, especially when MGMT is methylated.
Recurrent disease	150-200 mg/m2 Days 1-5 q28d or 50 mg/m2 daily 21 days on / 7 days off	Choice depends on prior exposure and marrow reserve.

Regulatory Status (U.S.)

• FDA-approved for newly diagnosed glioblastoma with radiation therapy (2005).
• FDA-approved for refractory anaplastic astrocytoma (1999).
• Off-label but guideline-supported in pediatric high-grade glioma and other CNS tumors.

Key Research Highlights

• Stupp 2005 (NEJM) - RT + TMZ vs RT alone: median OS 14.6 mo vs 12.1 mo.
• Intergroup low-grade glioma 10-year update – RT + TMZ OS 70 % vs 47 %.
• PARP-inhibitor combinations (e.g., veliparib) did not improve survival in phase III trials.

MGMT and Predictive Testing

MGMT-promoter methylation is the classic predictor of TMZ benefit. For tumors with unmethylated MGMT, the KIYATEC 3D-Predict Glioma assay cultures live tumor cells in a 3-D micro-environment and directly measures TMZ sensitivity. In a 2024 study the test identified a TMZ-responsive subgroup among MGMT-unmethylated patients, suggesting that TMZ may still be worthwhile if the assay is positive.

Further Reading

• Musella A. Brain Tumor Guide for the Newly Diagnosed, v12 - pp 156-159.
• Stupp R, et al. NEJM 2005;352:987-996.
• Detailed Temozolomide resource page: virtualtrials.org/temodar/.