Treatment > Chemotherapy
Most chemotherapeutic agents are incorporated into and alkylate the DNA of rapidly dividing tumor cells. These include the nitrosoureas, such as BCNU and PCNU, and drugs such as Procarbazine and Carboplatin. Drugs such as Vincristine poisons mitosis (the process by which one cell becomes two cells). Drugs such as VP-16 combined to tumor cell wall proteins and inhibit the production of microtubules - structures necessary for the life of the cell. Some chemotherapeutic agents also enhance the effect of radiation therapy such as Topotecan.
The problems with chemotherapy in brain tumors concern drug delivery and specificity. The effect of any chemotherapeutic agent is directly related to the dose given. Chemotherapy, usually given intravenously, adversely affects rapidly dividing tumor cells (which is good). However, chemotherapy can also affect rapidly dividing normal cells in the bowel and bone marrow. This results in nausea, vomiting and other gastrointestinal disturbances as well as bone marrow suppression with reduction of white blood cells (resulting in a reduced capacity to fight infection), red blood cells (anemia) and platelets (thrombocytopenia - resulting in blood clotting disorders and bleeding). The problem here is that chemotherapy injected into the patient's blood stream goes everywhere in addition to the brain and the tumor.
Other means of administering chemotherapy, such as directly into the arteries which supply the brain, have been investigated. The results of intra-arterial chemotherapy have been somewhat encouraging, but the complications and technical difficulties have prompted some to question its value. Wafers impregnated by a chemotherapeutic agent (BCNU) placed in the surgical cavity produced after removing a tumor have shown some encouraging results and have not been associated with as many systemic side-effects as other forms of chemotherapeutic administration. Incorporating other chemotherapeutic agents into polymers for local administration is being investigated.
One major problem in the chemotherapy of glial primary brain tumors is the fact that many tumor cells infiltrate surrounding brain tissue where the blood-brain barrier (which excludes large molecules) is intact. The chemotherapeutic agent can get to cells in the major mass of the tumor which is supplied by leaky tumor blood vessels. However, this tumor mass can also be removed by volumetric stereotaxis as described above. The blood-brain barrier protects tumor cells residing within intact brain tissue around the tumor. The blood-brain barrier, however, can be disrupted medically, and chemotherapy coupled with blood-brain barrier disruption shows some promise in the treatment of brain lymphoma and is under investigation in gliomas.