Temozolomide (Temodar)

Oral Alkylating Chemotherapy for Brain Tumors

What is Temozolomide? Temozolomide (brand name Temodar) is an oral chemotherapy drug used primarily to treat glioblastoma and other aggressive brain tumors. It works by damaging the DNA of cancer cells, preventing them from dividing and growing. Temozolomide is unique in its ability to cross the blood-brain barrier, making it one of the most important chemotherapy drugs for central nervous system cancers.
Drug Class
Alkylating Agent
Route
Oral (Capsule)
Main Use
Glioblastoma
FDA Approved
1999

How Temozolomide Works

Temozolomide is a prodrug, meaning it's inactive when you take it but converts to an active form in your body. Here's how it works:

The Mechanism

  1. Conversion to active form: After absorption, temozolomide spontaneously converts to MTIC (monomethyl triazeno imidazole carboxamide) at physiological pH
  2. DNA methylation: MTIC methylates (adds methyl groups to) DNA at multiple sites, most importantly the O6 position of guanine and the N7 position of guanine
  3. DNA damage: These methyl adducts cause DNA damage and trigger the cell's DNA repair mechanisms
  4. Cell death: If the damage is too extensive to repair, the cell dies (apoptosis)
Blood-Brain Barrier Penetration: Unlike most chemotherapy drugs, temozolomide readily crosses the blood-brain barrier, achieving nearly 100% of plasma concentration in cerebrospinal fluid. This makes it uniquely effective for brain tumors.

The Role of MGMT

One of the most important factors in how well temozolomide works is a protein called MGMT (O6-methylguanine-DNA methyltransferase):

Testing for MGMT: Your oncologist will test your tumor tissue for MGMT methylation status. This test helps predict how well temozolomide will work and guides treatment decisions. Even if MGMT is unmethylated, temozolomide is still used because it provides some benefit.

What is Temozolomide Used For?

FDA-Approved Uses

Common Off-Label Uses

How is Temozolomide Given?

The Stupp Protocol (Standard for Newly Diagnosed Glioblastoma)

This landmark regimen, published in 2005, dramatically improved survival for glioblastoma patients:

Phase 1: Concurrent Chemoradiation (6 weeks)
  • Temozolomide dose: 75 mg/m² daily, 7 days/week
  • Radiation: 60 Gy total, given in 30 fractions (2 Gy/day, Monday-Friday)
  • Duration: 42 days (6 weeks)
  • Timing: Take temozolomide 1 hour before radiation
  • PCP prophylaxis: Required (usually Bactrim 3 times/week)
Phase 2: Maintenance Chemotherapy (up to 12 months)
  • Break: 4 weeks off treatment after completing chemoradiation
  • Cycle 1 dose: 150 mg/m² daily for 5 days, every 28 days
  • Cycles 2-12 dose: 200 mg/m² daily for 5 days, every 28 days (if cycle 1 tolerated well)
  • Total cycles: Up to 12 cycles (some oncologists continue longer if tolerated)
  • Timing: Days 1-5 of each 28-day cycle

Dosing Schedule

Phase Dose Schedule Duration
Concurrent with radiation 75 mg/m² daily Every day during radiation 6 weeks
Maintenance - Cycle 1 150 mg/m² daily Days 1-5 of 28-day cycle 1 cycle
Maintenance - Cycles 2-12 200 mg/m² daily Days 1-5 of 28-day cycle Up to 11 cycles
Recurrent disease 150-200 mg/m² daily Days 1-5 of 28-day cycle Until progression

Alternative Dosing Schedules

Some oncologists use different schedules for recurrent disease or specific situations:

Important Administration Guidelines

How to Take Temozolomide:
  • Empty stomach: Take on an empty stomach (at least 1 hour before or 2-3 hours after eating) to reduce nausea and improve absorption
  • Bedtime dosing: Many patients take it at bedtime to "sleep through" nausea
  • Swallow whole: Don't open, crush, or chew capsules. If capsule breaks, avoid inhaling powder or getting it on skin
  • Anti-nausea medicine: Take ondansetron (Zofran) or other anti-emetic 30 minutes BEFORE temozolomide
  • Consistent timing: Take at the same time each day during the 5-day treatment period

Side Effects and Management

Most Common Side Effects (>30% of patients)

Serious Side Effects Requiring Monitoring

Call Your Doctor Immediately If You Experience:
  • Fever ≥100.4°F (38°C) - may indicate infection when blood counts are low
  • Unusual bleeding or bruising - easy bruising, nosebleeds, blood in urine/stool
  • Severe fatigue or weakness - may indicate anemia or very low blood counts
  • Shortness of breath, dry cough - could be PCP pneumonia or other lung infection
  • Severe headache, vision changes, seizures - may indicate tumor progression or complications
  • Persistent nausea/vomiting despite anti-nausea medications

1. Bone Marrow Suppression (Myelosuppression)

This is the MOST SERIOUS side effect of temozolomide:

Cumulative Effect: Bone marrow suppression can worsen with each cycle. Later cycles (especially cycles 6-12) often require dose reductions. This is normal and expected.

2. Pneumocystis jirovecii Pneumonia (PCP) Risk

Temozolomide causes severe lymphocyte depletion, increasing risk of this opportunistic infection:

PCP Prophylaxis is REQUIRED:
  • When: During the entire concurrent chemoradiation phase (6 weeks) and continue until lymphocyte recovery
  • Standard prophylaxis: Trimethoprim-sulfamethoxazole (Bactrim DS) 1 tablet 3 times per week
  • If sulfa allergy: Dapsone 100 mg daily or atovaquone (Mepron) 1,500 mg daily
  • Duration: Continue for at least 4 weeks after completing chemoradiation, or longer if lymphocyte count remains low

3. Nausea and Vomiting

Temozolomide is classified as moderate emetogenic risk:

4. Fatigue

Very common, especially during concurrent chemoradiation:

5. Hair Loss (Alopecia)

6. Other Side Effects

Monitoring During Treatment

Required Blood Tests

Test Frequency Purpose
Complete blood count (CBC) Weekly during concurrent phase; before each maintenance cycle and on day 21-22 of cycle Monitor bone marrow function
Comprehensive metabolic panel (CMP) Before each cycle Liver and kidney function
Lymphocyte count Weekly during concurrent phase Determine need for PCP prophylaxis

Imaging During Treatment

Dose Modifications

Temozolomide dose is reduced or held based on blood count nadirs:

Toxicity ANC Platelet Count Dose Modification
Grade 0-2 ≥1,500/µL ≥100,000/µL Increase to/maintain 200 mg/m²
Grade 3 1,000-1,499/µL 50,000-99,999/µL Reduce by 50 mg/m² (or maintain 150 mg/m²)
Grade 4 <1,000/µL <50,000/µL Hold temozolomide; reduce by 50 mg/m² when resume

How Well Does Temozolomide Work?

The Stupp Trial: A Landmark Study

The 2005 EORTC-NCIC trial (led by Dr. Roger Stupp) revolutionized glioblastoma treatment:

Survival Improvement with Temozolomide:
  • Median survival: 14.6 months with radiation + temozolomide vs. 12.1 months with radiation alone
  • 2-year survival: 27% vs. 11%
  • 5-year survival: 9.8% vs. 1.9% (nearly 5-fold improvement!)
  • Impact: This combination became the standard of care worldwide and remains so today

MGMT Status and Outcomes

The benefit of temozolomide varies significantly based on MGMT methylation:

MGMT Status Median Survival with TMZ+RT 2-Year Survival Temozolomide Benefit
Methylated (~45% of patients) 21-24 months ~48% Substantial benefit
Unmethylated (~55% of patients) 12-15 months ~15% Modest benefit
Important: Even with unmethylated MGMT, temozolomide still provides some benefit and remains standard of care. There are no better alternatives currently available.

Long-Term Survivors

While glioblastoma remains a very difficult cancer to treat, there are long-term survivors:

How Long is Treatment?

Standard Duration

Extended Treatment

Some evidence suggests benefit from continuing beyond 12 cycles:

Stopping Treatment

Treatment is typically stopped if:

Drug Interactions and Precautions

Important Drug Interactions

Medications to Support Treatment

Most patients on temozolomide take several supportive medications:

Special Populations

Storage and Handling

Chemotherapy Safety:
  • Store capsules: Room temperature (68-77°F), away from moisture and light
  • Keep in original bottle: Don't transfer to pill organizers (capsules can degrade)
  • If capsule breaks: Don't touch powder. Clean up with wet paper towels and dispose in sealed plastic bag. Wash hands thoroughly
  • Safe handling: Some oncologists recommend wearing gloves when handling capsules if you're sensitive
  • Disposal: Return unused capsules to pharmacy for proper disposal. Don't flush down toilet
  • Keep away from children and pets

Cost and Insurance Coverage

Medication Cost

Insurance Coverage

Financial Assistance

Alternatives and Comparisons

Other Chemotherapy Options for Glioblastoma

Emerging Therapies

Recent Advances and Ongoing Research

Combination Approaches

Understanding Resistance

Novel Dosing Strategies

Frequently Asked Questions

Q: Can I drink alcohol while taking temozolomide?
A: It's best to avoid or minimize alcohol consumption during temozolomide treatment. Alcohol can increase nausea, interact with anti-seizure medications many brain tumor patients take, and may worsen liver enzyme elevations. If you do drink, limit to small amounts and discuss with your oncologist. Avoid alcohol completely if you have liver problems or are taking medications that interact with alcohol.
Q: What if I miss a dose?
A: If you miss a dose and remember the same day, take it as soon as you remember (still on empty stomach). If you don't remember until the next day, skip the missed dose and take your next dose as scheduled. Do NOT take two doses at once. Call your oncology team to let them know you missed a dose - they may adjust your schedule.
Q: Why do I need to take antibiotics (Bactrim) with temozolomide?
A: Temozolomide causes severe lymphocyte depletion, especially during the concurrent chemoradiation phase. This puts you at high risk for Pneumocystis jirovecii pneumonia (PCP), a potentially life-threatening infection. Bactrim or equivalent antibiotic prevents PCP. This is not optional - it's a critical safety measure. Continue Bactrim for the entire concurrent phase and usually 4+ weeks after until your lymphocyte count recovers.
Q: Can temozolomide cure my glioblastoma?
A: Honestly, cure is rare with current treatments. Glioblastoma typically recurs even after maximal treatment. However, temozolomide combined with surgery and radiation has dramatically improved survival - the 5-year survival rate has increased from ~2% to ~10%, and some patients (~15-20% with favorable factors like MGMT methylation and complete resection) survive even longer. Every year of research brings us closer to better treatments. The goal is to control the tumor as long as possible and maintain quality of life.
Q: Should I continue temozolomide beyond 12 cycles if I'm tolerating it well?
A: This is a common question and there's no definitive answer. The standard Stupp protocol uses 6-12 cycles. Some retrospective studies suggest possible benefit from continuing to 18-24 cycles if tolerated. However, cumulative bone marrow toxicity often becomes limiting. Discuss with your neuro-oncologist, considering your individual factors: disease control on MRI, blood counts, tolerance of treatment, your personal preferences. Some doctors continue if stable disease and acceptable blood counts; others stop at 12 cycles per protocol.
Q: Why does my MRI show tumor growth when I feel fine? Could it be pseudoprogression?
A: Pseudoprogression occurs in 20-30% of patients, typically 2-3 months after completing radiation. Inflammation from treatment can look exactly like tumor growth on standard MRI. This is why your oncologist may recommend continuing treatment and repeating MRI in 4-6 weeks, or using advanced imaging (MRI perfusion, MR spectroscopy, PET scan) to help distinguish pseudoprogression from true progression. Clinical symptoms also help - if you feel well with no new neurologic symptoms, pseudoprogression is more likely. True progression usually (but not always) causes symptoms.
Q: Can I take vitamins and supplements during temozolomide treatment?
A: Most standard vitamins and minerals are fine (multivitamin, vitamin D, calcium). However, AVOID high-dose antioxidant supplements (vitamin C, vitamin E, beta-carotene in megadoses) as they may theoretically interfere with chemotherapy's ability to damage cancer cells. Also avoid St. John's Wort and many herbal supplements that can interact with medications. Always tell your oncologist about ALL supplements you're taking - bring bottles to appointments. Vitamin B6 (pyridoxine) is sometimes recommended but check first.
Q: My hair is thinning. Will I go completely bald?
A: Temozolomide typically causes mild to moderate hair thinning, not complete baldness like traditional IV chemotherapy regimens. However, you're also receiving brain radiation, which causes permanent hair loss in the radiation field (usually where the tumor is located). The combination means you'll likely have significant thinning or hair loss, especially in the radiated area. Hair outside the radiation field usually grows back after treatment ends. Some patients choose to get a short haircut or wear hats/scarves during treatment.
Q: Is generic temozolomide as effective as brand-name Temodar?
A: Yes. Generic temozolomide must meet the same FDA standards for bioequivalence as brand-name Temodar. Multiple studies have confirmed equivalent clinical outcomes. The active ingredient and absorption are the same. The main difference is cost - generic is much less expensive. Insurance companies typically require generic unless there's a specific medical reason for brand-name. If you have concerns, discuss with your oncologist, but generics are medically appropriate and widely used.
Q: What happens if temozolomide stops working?
A: If glioblastoma progresses during or after temozolomide, several options exist depending on your specific situation: (1) Bevacizumab (Avastin) alone or with lomustine, (2) Re-operation if feasible, (3) Re-irradiation in select cases, (4) Clinical trial of novel therapy, (5) Alternative chemotherapy (lomustine, carboplatin, irinotecan), (6) Focus on quality of life and symptom management. Your neuro-oncologist will discuss options based on your tumor location, prior treatments, functional status, and personal goals. Some patients choose supportive care over additional aggressive treatment.

Living with Temozolomide Treatment

Practical Tips for Daily Life

When to Call Your Doctor

Contact your oncology team immediately for:
  • Fever ≥100.4°F (38°C)
  • New or worsening neurologic symptoms (weakness, numbness, vision changes, speech problems, seizures)
  • Severe headache different from usual
  • Unusual bleeding or bruising
  • Shortness of breath or new cough
  • Persistent nausea/vomiting despite medications
  • Signs of infection (cough, burning with urination, skin redness/warmth)

Support Resources

Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Every patient's situation is unique. Always consult your neuro-oncologist and healthcare team about your specific condition, treatment plan, and any questions or concerns you have. Treatment protocols and recommendations may vary based on individual patient factors, tumor characteristics, and the latest research. If you have a medical emergency, call 911 or go to the nearest emergency room immediately.
Sources: This guide is based on FDA prescribing information, National Comprehensive Cancer Network (NCCN) guidelines for central nervous system cancers, landmark clinical trials including the EORTC-NCIC trial (Stupp et al.), peer-reviewed medical literature, and clinical practice guidelines from major cancer centers. Content reviewed for medical accuracy and updated to reflect current standards of care as of 2025.