The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

Chemotherapy for brain metastases has been considered ineffective because the drugs do not penetrate the intact blood brain barrier. Alternate explanations for past failures of chemotherapy include observations that 1) many solid tumors which metastasize to brain are drug-resistant regardless of location, 2) brain metastases often occur following failure of primary chemotherapeutic regimens to control systemic metastases, and 3) previous trials of chemotherapy employed agents other than those known to be most effective against the primary malignancy. Furthermore, laboratory studies have demonstrated that cytoxic levels of many drugs can be measured in tumor tissue from primary and metastatic brain tumors. These clinical and pharmacologic observations suggest that chemotherapy would be expected to have limited value unless known effective combination regimens are employed as first-line therapy in chemosensitive malignancies. Recent reports of chemotherapy for patients with brain metastases from small cell lung carcinoma, gestational choriocarcinoma, germ cell malignancies, and breast carcinoma do describe response rates in the brain similar to those in other organ sites. In conclusion, chemotherapy for cerebral metastases can be expected to be effective only when effective drugs for systemic metastases are available. While the blood-brain barrier may be an additional detriment to successful treatment, other factors may be more important.