Chemotherapy and cerebral metastases: misperception or reality?

Cerebral metastases remain a common complication among patients with cancer. Surgery and radiotherapy remain the principal therapeutic interventions. In contrast, the benefit of chemotherapy has long been viewed with skepticism. Nonetheless, as survival in cancer patients improves and the incidence of cerebral metastases increases, so does the demand for effective therapies. It is now recognized that the blood-brain barrier within metastases is permeable and thus allows entry of otherwise excluded drugs. Limited data have suggested that cerebral metastases have modest sensitivity to chemotherapy. Furthermore, novel agents and delivery strategies have been developed to facilitate central nervous system penetration. Nonetheless, data are limited by methodological flaws, including heterogeneous inclusion criteria, small sample sizes, lack of randomization, and inconsistencies in defined end points and response assessment criteria. Well-designed clinical trials are needed to address the effect of chemotherapy. Acceptable control arms must be established to measure the effect of chemotherapies. Standardized response criteria and disease-specific studies are essential.