Temozolomide
TEMODAR
What it isAn oral alkylating agent that methylates DNA guanine, standard with radiation for glioblastoma and for other gliomas.
Why this oneIt crosses the blood-brain barrier and is taken as capsules — chemotherapy for brain tumors without an infusion chair — and benefit is greatest when the tumor has silenced its MGMT repair enzyme.
What limits itMyelosuppression, especially thrombocytopenia, gates each cycle, and the prolonged lymphopenia obliges Pneumocystis prophylaxis during chemoradiation.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Newly diagnosed glioblastoma — concomitant phase (with focal radiotherapy) | Adults | 75 mg/m2 QD x42-49 days | 75 mg/m2 QD through radiotherapy | 75 mg/m2 QD |
| Newly diagnosed glioblastoma — maintenance (begin 4 wk after concomitant phase) | Adults | Cycle 1: 150 mg/m2 QD days 1-5 of 28-day cycle | 200 mg/m2 QD days 1-5, cycles 2-6 (if cycle 1 tolerated) | 200 mg/m2 QD days 1-5 |
| Newly diagnosed anaplastic astrocytoma — adjuvant (begin 4 wk after radiotherapy) | Adults | Cycle 1: 150 mg/m2 QD days 1-5 of 28-day cycle | 200 mg/m2 QD days 1-5, cycles 2-12 (if no/minimal toxicity in cycle 1) | 200 mg/m2 QD days 1-5 |
| Refractory anaplastic astrocytoma | Adults | 150 mg/m2 QD days 1-5 of 28-day cycle | 200 mg/m2 QD days 1-5 (if ANC ≥1.5 and platelets ≥100 x10^9/L at nadir and day 1) | 200 mg/m2 QD days 1-5 |
Titration Escalate 150 → 200 mg/m2 only at start of Cycle 2 if cycle 1 tolerated (no interruptions; counts adequate); if not escalated at Cycle 2, do not escalate in later cycles
Renal CLcr 36-130 mL/min/m2: no adjustment; severe impairment (CLcr <36) or dialysis: not established
Hepatic Mild-moderate (Child-Pugh A/B): no adjustment; severe (C): not established
Cycle length 28 days; do not start next cycle until ANC >1.5 and platelets >100 x10^9/L
Instructions
- Withhold dosing until ANC ≥1.5 x10^9/L and platelets ≥100 x10^9/L; CBC weekly during concomitant RT; CBC day 1 and day 22 of each 28-day cycle, then weekly until recovery
- PCP prophylaxis for all patients during the concomitant phase; continue if lymphopenia develops until ≤Grade 1
- If dose withheld during maintenance, reduce next cycle by 50 mg/m2/day; permanently discontinue if 100 mg/m2/day not tolerated
- Swallow capsules whole with water; do not open, chew, or dissolve (hazardous drug); take at same time each day, consistently with respect to food; empty stomach or bedtime dosing and antiemetics reduce nausea/vomiting
Contraindications
- History of hypersensitivity to dacarbazine (both metabolized to the same active metabolite, MTIC)
Cautions
- Myelosuppression, some fatal (nadirs ~day 26-28; higher risk in geriatric patients and women) — monitor CBC per schedule
- Fatal and severe hepatotoxicity — LFTs at baseline, midway through cycle 1, before each cycle, and 2-4 weeks after last dose
- Pneumocystis pneumonia — risk increased with steroids and longer regimens; prophylaxis during concomitant phase; monitor for lymphopenia
- Secondary malignancies (MDS, myeloid leukemia)
- Embryo-fetal toxicity — contraception during and 6 months after (females); condoms and no semen donation during and 3 months after (males)
- Do not open capsules — avoid inhalation/skin contact with powder
Adverse reactions
- Alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, convulsions
- Grade 3-4: lymphopenia (55% refractory AA), thrombocytopenia, neutropenia, leukopenia
- Postmarketing: SJS/TEN, prolonged pancytopenia/aplastic anemia (fatal), hepatotoxicity, opportunistic infections (some fatal), interstitial pneumonitis/pulmonary fibrosis, diabetes insipidus
Pregnancy Can cause fetal harm; postmarketing reports of spontaneous abortion and congenital polymalformations; verify pregnancy status before starting
Lactation Do not breastfeed during treatment and for at least 1 week after last dose
NO BOXED WARNINGS
Classes and tags
Clinical profile
Mechanism of action: Temozolomide ballicule
