Systemic chemotherapy for a primary germ cell tumor of the brain: a pharmacokinetic study

Systemic administration of most chemotherapeutic agents has been assumed to be ineffective in the treatment of primary and metastatic brain tumors because these agents fail to cross the intact blood-brain barrier. However, agents which fail to penetrate the intact blood-brain barrier may penetrate it under conditions which include the presence of tumor in the central nervous system (CNS) and prior CNS irradiation. This paper reports the results of pharmacokinetic studies of bleomycin, cisplatin, and vinblastine in the CNS of a patient with a primary germ cell tumor of the brain who had received prior radiotherapy. Significant concentrations of bleomycin and cisplatin, but not of vinblastine, were reached in the cerebrospinal fluid (CSF) of the patient following iv administration. The area under the bleomycin CSF concentration times time curve was 25% of the area under the bleomycin plasma concentration times time curve. The areas under two cisplatin CSF curves were 50% and 155% of the areas under the corresponding free cisplatin plasma curves. Moreover, an objective response of the tumor to the chemotherapy was documented. This study provides evidence that, under certain circumstances, significant concentrations of cisplatin and bleomycin may be obtained in human CSF following systemic administration and that it may be possible to treat primary or metastatic CNS tumors with agents effective against systemic tumor of the same histologic type.