For persons with lymphoma of the brain, a cancer of the lymph system that manifests in the brain, it is important that the anti-cancer treatments used are able to penetrate into the brain tissue, without damaging the brain tissue. However, drug penetration to the brain can be difficult because of the natural protective barrier of the brain called the blood-brain barrier. Now, researchers in Australia say that the use of high doses of a chemotherapy drug called methotrexate, given intravenously, can reach and treat the brain tissue. A drug called leucovorin, given after the methotrexate, is used to protect the brain from any damage the high-dose methotrexate might cause.

Primary lymphoma of the brain is a type of cancer that is characterized by the uncontrolled multiplication of lymphocytes (cells produced in the lymph system), which manifest in the brain. This disease is increasing in incidence in persons with AIDS because their immune systems are weakened by the HIV virus. However, lymphoma of the brain also occurs in persons who do not have AIDS. In terms of treatment, cancer cells may be present in various parts throughout the brain; therefore, surgery is usually not helpful. In addition, the protective blood-brain barrier makes it difficult for drugs, such as those used in chemotherapy, to reach the brain. A commonly used treatment for lymphoma of the brain is radiation to the brain plus an injection of methotrexate directly into the spinal fluid (the fluid that surrounds the spine and brain). This therapy can achieve long remissions (absences of the signs and symptoms of cancer) for some persons; however, the cancer can recur (return) and the side effects from the injected methotrexate with radiation therapy can be significant. To try to improve the treatment’s effectiveness and reduce its side effects, researchers have developed another method of delivering methotrexate to the brain.

By administering high doses of methotrexate intravenously (through the blood vessels), the drug is able to penetrate through the blood-brain barrier, to the brain tissue. Because the methotrexate may damage not only the cancer cells, but also the brain tissue, an antidote drug called leucovorin is administered 6 hours after the methotrexate to reverse any side effects that may occur. Researchers in Australia treated 46 persons with primary lymphoma of the brain that was not associated with AIDS. The patients received 2 doses of methotrexate, 1 week apart, followed 6 hours later by an infusion of leucovorin. After the chemotherapy, patients underwent radiation therapy to the brain. Results showed an average survival time of 33 months, with the 2-year survival rate being 62%. Any recurrences (return of the cancer) occurred predominantly in the brain. Side effects included toxic effects in the brain in 6 persons, 3 of whom died.

The researchers concluded that 2 high doses of intravenous methotrexate, followed by radiation therapy to the brain, may decrease the risk of recurrence for persons with primary lymphoma of the brain, but may also cause significant side effects to the brain tissue. Persons who have lymphoma of the brain may wish to talk with their doctor about the risks and benefits of the intravenous methotrexate/leucovorin regimen, or of participating in a clinical trial in which other new treatments are being studied. Other sources of information on ongoing clinical trials include a comprehensive, easy-to-use service provided by the National Cancer Institute ( and the Clinical Trials section and service offered by Cancer Treatment ( (Journal of Clinical Oncology, Vol 18, No 3, pp 519-526, 2000)

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