Chemotherapy plays an expanding role in the management of recurrent disease and in many newly diagnosed patients. Two anatomic features of the CNS make it unique with respect to the delivery of chemotherapeutic agents:
1. The tight junction of the endothelial cells of the cerebral capillaries, that is, the blood-brain barrier
The blood-brain barrier inhibits the equilibration of large polar lipid-insoluble compounds between the blood and brain tissue, whereas small nonpolar lipid-solu-ble drugs rapidly equilibrate across the blood-brain barrier. The blood-brain barrier is probably not crucial in determining the efficacy of a particular chemotherapeutic agent, because in many brain tumors the normal blood-brain barrier is impaired. Factors such as tumor heterogeneity, cell kinetics and drug administration, distribution, and excretion play a more significant role in determining the chemotherapeutic sensitivity of a particular tumor than does the blood-brain barrier. Tumors with a low mitotic index and small growth fraction are less sensitive to chemotherapy; tumors with a high mitotic index and larger growth fraction are more sensitive to chemotherapy.
The CSF circulates over a large surface area of the brain and provides an alternate route for drug delivery; it can function as a reservoir for intrathecal administration or as a sink after systemic administration of chemotherapeutic agents. The rationale of instillation of chemotherapy into the CSF compartment is that significantly higher drug concentrations can be attained in the CSF and surrounding brain tissue. This mode of administration is most applicable in cases of meningeal spread or in those tumors in which the risk of spread through the CSF is high.
Adjuvant chemotherapy is used in select primary brain tumors and for recurrent disease (Table 17-4). In certain cases it allows for decreased radiation doses with equal or improved cure rates. In others, adjuvant chemotherapy improves outcome with standard radiation therapy. Trials of new agents, combinations of agents, and standard drugs as radiosensitizing agents are ongoing.
Was this article helpful?