Temozolomide is an oral chemotherapy drug, sold under brand names like Temodar, used to treat specific types of brain tumors. This medication is a type of drug known as an alkylating agent and is administered in capsule form for cancers originating in the brain.
Cancers Treated by Temozolomide
Temozolomide is used for specific, aggressive brain tumors. The U.S. Food and Drug Administration (FDA) has approved its use for newly diagnosed glioblastoma multiforme, the most common and aggressive type of primary brain tumor in adults. It is used at the same time as radiation therapy and then continued as a maintenance treatment.
The drug is also FDA-approved for anaplastic astrocytoma, another form of malignant glioma, that has not responded to initial treatments or has returned after standard therapy. Temozolomide may be used “off-label” for other cancers, such as melanoma that has metastasized, or spread, to the brain, because of the drug’s ability to reach brain tissue.
Mechanism of Action
Temozolomide is an alkylating agent that functions by interfering with the DNA of cancer cells. The medication is a “prodrug,” meaning it is converted into its active, cancer-fighting form within the body through a chemical reaction. This active compound, known as MTIC, then adds small molecular clusters called methyl groups to the DNA of the tumor cells.
This addition of methyl groups damages the cancer cell’s genetic material, creating “nicks” in the DNA. The damage disrupts the cell’s ability to read its own genetic code, preventing it from dividing and creating new cells. This process triggers a form of programmed cell death called apoptosis, which helps to slow or stop the growth of the tumor.
Temozolomide’s chemical structure allows it to effectively cross the blood-brain barrier. This protective membrane shields the brain from many substances in the bloodstream, but temozolomide’s small, fat-soluble molecules can penetrate it. This ability allows the drug to reach tumors within the brain at concentrations high enough to be effective.
Administration and Dosing Schedule
Temozolomide is administered as an oral capsule, though an intravenous (IV) formulation is also available. Patients are instructed to take the capsules on an empty stomach, at least one hour before a meal, to help with the drug’s absorption into the bloodstream. The capsules should be swallowed whole with water and should not be opened or chewed.
Treatment with temozolomide is cyclical, meaning periods of taking the drug are followed by rest periods. A frequent schedule for maintenance therapy is the “5/28 cycle,” where the patient takes the medication once daily for five consecutive days, followed by a 23-day break.
The rest period gives the body’s healthy cells, which can also be affected by the chemotherapy, time to recover from the drug’s effects. The specific dosage is calculated based on a person’s body surface area and may be adjusted based on blood test results and how well the treatment is tolerated.
Common Side Effects and Management
Patients taking temozolomide can experience a range of side effects, with the most frequent being nausea, vomiting, fatigue, constipation, and headaches. Loss of appetite is also common. To manage the nausea and vomiting, doctors often prescribe anti-emetic medications to be taken before or after the chemotherapy dose.
A more significant effect of temozolomide is myelosuppression, which is a decrease in the bone marrow’s ability to produce blood cells. This can lead to low counts of white blood cells (neutropenia), which increases the risk of infection.
It can also cause low levels of platelets (thrombocytopenia), which are needed for blood clotting and can result in easier bruising or bleeding. In some instances, it can also lead to a low red blood cell count, known as anemia. While many of these side effects are manageable, some can be more severe. In rare cases, prolonged low blood counts can occur, which may require treatment adjustments.
Important Patient Precautions
Before starting temozolomide, patients should inform their healthcare team of any pre-existing medical conditions, particularly liver or kidney problems, or a history of hepatitis B infection. Temozolomide can cause the hepatitis B virus to become active again. Patients should also provide a complete list of all other medications they are taking, as some drugs can interact with the chemotherapy.
Regular blood tests are performed before starting and throughout the treatment cycle to closely monitor blood cell counts. If counts of white blood cells or platelets drop too low, the doctor may need to adjust the dose or delay the next treatment cycle to allow the body to recover.
For patients receiving temozolomide at the same time as radiation, or those on longer treatment schedules, there is an increased risk of a specific type of lung infection called Pneumocystis jirovecii pneumonia (PCP). To prevent this, doctors often prescribe a preventative antibiotic. Due to potential risks to a developing fetus, effective birth control is recommended for both men and women during treatment and for a period of time after the final dose.