Chemotherapy uses drugs to kill or alter cancer cells. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs have a hard time passing into the brain because of the blood-brain barrier that normally protects the brain from harmful chemicals. In addition, not all types of brain tumors respond to chemotherapy. In general, chemotherapy for brain tumors is usually administered following surgery or radiation therapy.
The type of drug determines how it is administered. "Systemic delivery" drugs, which pass to the brain from the bloodstream, may be given by mouth, injected into a vein through an IV, or injected into an artery or a muscle. "Local delivery" drugs are placed within or around the brain tumor.
Newer delivery methods to overcome some of these problems include:
Interstitial chemotherapy uses disc-shaped polymer wafers (known as Gliadel wafers) soaked with carmustine, the standard chemotherapeutic drug for brain cancer. The surgeon implants the wafer directly into the surgical cavity after a tumor is removed.
Intrathecal chemotherapy delivers chemotherapeutic drugs directly into the spinal fluid.
Intra-arterial chemotherapy delivers high-dose chemotherapy into arteries in the brain using tiny catheters.
Convection-enhanced delivery (CED) involves placing catheters into the brain tumor or nearby brain tissue to deliver slowly and continuously a cancer drug over several days.
Chemotherapy Drugs and Regimens
Many different drugs, and drug combinations, are used for chemotherapy. Standard ones include:
Temozolomide (Temodar, generic). Temozolomide is used for adult patients with anaplastic astrocytoma that did not respond to other treatments. It is used during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. The current first-line treatment for patients with glioblastoma is combined radiotherapy and temozolomide, followed by monthly doses of temozolomide after radiation treatment ends. The drug may work best for patients with a specific genotype. Temozolomide's side effects are relatively minor, but may include constipation, nausea and vomiting, fatigue, and headache. The drug is taken by mouth as a pill.
Carmustine (BCNU, BiCNU). Carmustine is used to treat many types of brain tumors, including glioblastoma, medulloblastoma, and astrocytoma. Carmustine is usually administered into the vein by IV. It can also be delivered through a wafer implant (Gliadel), which is surgically placed into the brain cavity after tumor removal. If carmustine is administered intravenously, side effects may include nausea and vomiting, fatigue, respiratory problems, and lung scarring (pulmonary fibrosis). Intravenous carmustine may cause bone marrow impairment, which results in decreased production of blood cells (a condition called myelosuppression). If carmustine is delivered through a wafer, side effects may include seizures, brain swelling, and infection within the brain cavity.
PCV Drug Regimen. PCV is an abbreviation for a chemotherapy regimen that combines procarbazine (Matulane), lomustine (Ceenu, CCNU), and vincristine (Oncovin, generic). PCV is commonly used to treat oligodendrogliomas and mixed oligoastrocytomas. The drugs may also be used alone or in other combinations. Procarbazine and lomustine are taken by mouth. Vincristine is given by either injection or IV. These drugs can cause significant side effects, including a drop in blood cell counts, nausea and vomiting, constipation, fatigue, and mouth sores. Procarbazine can cause high blood pressure when taken with foods high in tyramine. Patients should avoid foods such as beer, red wine, cheese, chocolate, processed meat, yogurt, and certain fruits and vegetables.
Platinum-Based Drugs. Cisplatin (Platinol, generic) and carboplatin (Paraplatin, generic) are standard cancer drugs that are sometimes used to treat glioma, medulloblastoma, and other types of brain tumors. These drugs are delivered by IV. In addition to nausea and vomiting, carboplatin can cause hair loss, and cisplatin can cause muscle weakness.
Other Chemotherapy Drugs. Researchers are investigating whether drugs used to treat other types of cancer may have benefits for brain tumors. These drugs include:
- Tamoxifen (Nolvadex, generic) and paclitaxel (Taxol, generic), which are used to treat breast cancer
- Topotecan (Hycamtin, generic), which is used to treat ovarian and lung cancers
- Vorinostat (Zolinza), which is approved for treatment of cutaneous T-cell lymphoma
Irinotecan (Camptostar, generic) is another cancer drug that is being studied in combination treatment.
Biologic Drugs (Targeted Therapy)
Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells they can cause severe side effects. Targeted biologic therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, these biologic drugs may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotype.
Bevacizumab (Avastin). Bevacizumab (Avastin) is a biologic drug that blocks the growth of blood vessels that feed tumors (a process called angiogenesis). It is approved for the treatment of glioblastoma in patients whose brain cancer has continued to progress after prior treatment with chemotherapy and radiation. Bevacizumab was the first targeted therapy approved for brain tumors, and the first new treatment for glioblastoma in more than a decade. Some recent studies have questioned its effectiveness.
Investigational Targeted Therapies. Targeted therapies being tested in clinical trials include:
- Vaccines are among the most promising immunotherapies being tested for slowing the progression of glioblastoma multiforme. Unlike conventional vaccines that are used to prevent disease, these vaccines are used as a cancer treatment. CDX-110 (Rindopepimut) and DCVax-Brain are two such vaccines.
- Tyrosine kinase inhibitor drugs block proteins involved in tumor cell growth and production. Tyrosine kinase inhibitors that target EGFR [such as erlotinib (Tarceva), imatinib (Gleevec), and gefitinib (Iressa)] are being studied for their effects on brain tumors.
- MTOR inhibitors target other enzymes involved in cell growth and replication. These drugs are commonly used to suppress the immune system to prevent rejection after organ transplantation. Everolimus (Afinitor, Afinitor Disperz) is approved for treatment of benign brain tumors associated with a rare genetic condition and for treatment of a rare pediatric brain tumor called subependymal giant cell astrocytoma (SEGA). Everolimus is related to sirolimus (Rapamune) and tacrolimus (Prograf, generic), which are also being investigated for brain tumor treatment.