Brain Tumors: Primary - Chemotherapy

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Temozolomide (Temodar). Temozolomide, the first new drug approved for brain tumors in several decades, may improve quality of life and increase the time to progression for many patients with malignant gliomas. Temozolomide is taken by mouth and has relatively few side effects. In 1999, it was approved for adult patients with anaplastic astrocytoma that did not respond to other treatments. In 2005, it was approved for use during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. It is showing promise for recurrent high-grade gliomas, anaplastic oligodendrogliomas, and low-grade astrocytomas. It has only modest and short-lived effects on recurrent gliomas. Clinical trial results presented at the 2004 American Society of Clinical Oncology (ASCO) meeting confirm that temozolomide administered during and after radiation is a first-line treatment for glioblastoma multiforme. A 2005 study, published in the New England Journal of Medicine, reported that adults with newly diagnosed glioblastoma who received temozolomide during and after radiation therapy had a higher rate of 2-year survival than patients who received radiation alone.

Other Chemotherapy Drugs Used or Investigated for Recurring or High-Grade Cancers

Several drugs and treatments are being tested or used for primary and recurring tumors.

• Tamoxifen, a breast-cancer drug, may benefit some patients with glioma when administered continuously at high doses. More research is needed to determine which patients may benefit.
• High-dose thiotepa along with bone marrow or stem cell transplantation is being tested for newly diagnosed aggressive oligodendroglioma as an alternative to radiotherapy. Although some patients have prolonged disease-free survival time, thiotepa has very toxic side effects, including encephalopathy (brain damage), liver damage, severe weight loss, and a drop in blood platelet count. High-dose thiotepa along with bone marrow or stem cell transplantation is being investigated for recurrent aggressive oligodendroglioma.
• Paclitaxel (Taxol), a drug used for breast cancer, is also being investigated for gliomas. It is showing promise for patients with recurrent gliomas. In one study, paclitaxel with stereotactic radiosurgery improved results for patients with glioblastoma multiforme.
• Topo I inhibitors block topoisomerase I, an enzyme involved in cell replication. Clinical studies have shown that the Topo I inhibitors topotecan and irinotecan injure brain tumor cells. Combinations of Topo I inhibitors with standard chemotherapy drugs, such as BCNU, is proving to be effective for some patients. Some studies suggest it may help some children with gliomas. They may also be important drugs in radiochemotherapy. Less positive studies on irinotecan report that combinations with anti-seizure medications reduce its effectiveness.
• 5-fluorouracil (5-FU) is a standard chemotherapy drug for numerous malignancies. It has not, to date, been useful for brain tumors because, like most of these drugs, it cannot pass the blood brain barrier. A new form (Ethypharm), however, employs a microsphere containing the drug that is implanted in the tissue. Early studies are promising. Investigators are also looking at genetic therapies to deliver the drug directly to the tumor.
• Carboplatin with or without vincristine is being studied for low-grade progressive gliomas, which are difficult to treat with surgery or radiation.