Intracranial Tumours Management

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CHEMOTHERAPY

Chemotherapeutic agents have been used for many years in the management of malignant brain tumours, but clinical benefits remain uncertain.

Drugs most commonly employed include nitrosureas (e.g. BCNU, CCNU, methyl-CCNU) procarbazine, vincristine and methotrexate.

Patients with malignant tumours can show a response to chemotherapy. When used as part of primary therapy a statistically significant prolongation of survival may result. The side effects of the treatment however leave the value of the few extra weeks gained in doubt. In malignant astrocytoma, the Nitrosoureas e.g. BCNU, are the most active drugs and are commonly used for the treatment of relapsed patients. Chemotherapy for benign or low grade tumours is of limited value. Medulloblastoma commonly responds to treatment, but its value in improving patients' survival is unclear. Chemotherapy does appear to have a role in primary germ cell tumours and in primary cerebral lymphoma.

Problems of drug administration

Toxicity: The ideal cytotoxic drug selectively kills tumour cells; but tumour cell response relates directly to the dose. High drug dosage causes bone marrow suppression. Often marrow depression occurs before an adequate therapeutic dose is reached.

Drug access: 'Toxic' doses are usually required before sufficient amounts penetrate the blood-brain barrier and gain access to the tumour cells.

Intrinsic resistance: Some tumour cells appear to have an inbuilt resistance to certain drugs. The vast array of available cytotoxic drugs and the infinite permutations of combined therapy creates difficulties in drug selection.

New approaches

Cell targeting: Monoclonal antibodies have been used in the hope that they would serve as carriers, taking cytotoxic drugs, toxins or radionuclides directly to the tumour site. Initial studies on intrinsic tumours have not lived up to expectations due to problems with access and transfer across the blood-brain barrier.

Improving access: Modifying the blood-brain barrier with mannitol or preliminary binding with liposomes may improve the passage of cytotoxic drugs and monoclonal antibodies to tumour tissue. Similarly direct intracarotid injection may improve access over conventional routes of administration. A recent study has suggested modest benefit from the intraoperative placement of 'slow release' biodegradable polymers of BCNU in patients with malignant glioma. These methods await full evaluation.

In vitro chemosensitivity testing: This approach utilises cultured tumour cells from biopsy material. In vitro analysis of growth inhibition, or the rate of cell death following application of a specific drug, points to the tumour 'sensitivity' of the drug under test. In practice, this technique appears to be of limited value. Although successfully identifying drugs which have no effect on the tumour, the demonstration of cytotoxic activity in vitro does not always reflect its in vivo performance.

PROGNOSIS OF INTRACRANIAL TUMOURS

Patient prognosis depends on the specific tumour type; this is described for individual tumours on subsequent pages.

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