TOXICITY AND EFFICACY OF CARBOPLATIN AND ETOPOSIDE IN CONJUNCTION WITH DISRUPTION OF THE BLOOD-BRAIN TUMOR BARRIER IN THE TREATMENT OF INTRACRANIAL NEOPLASMS

CARBOPLATIN AND ETOPOSIDE have been investigated in preclinical studie s and a limited toxicity study in 13 patients; these studies have esta blished carboplatin and etoposide as a tolerable combination when admi nistered with blood-brain barrier disruption. The studies also found a predictable dose-limiting toxicity of myelosuppression. Subsequently, a broad efficacy trial of this regimen was carried out. A total of 34 patients, ranging in age from 7 to 72 years, underwent a combination chemotherapy regimen of carboplatin (200 mg/m(2) administered intra-ar terially) and etoposide (200 mg/m(2) administered intravenously) admin istered with blood-brain barrier disruption on each of 2 consecutive d ays every 28 days. The diagnoses included glioblastoma multiforme (n = 3), malignant astrocytoma (n = 8), malignant astrocytoma-oligodendrog lioma (n = 1), primitive neuroectodermal tumor (n = 4), disseminated g erm cell tumor of the central nervous system (CNS) (n = 6), CNS lympho ma (n = 7), and metastatic carcinoma (n = 5). The major toxicity obser ved in patients treated with multiple courses of this regimen was the expected reversible myelosuppression and an unexpected, irreversible h igh-frequency hearing loss. Of these 34 patients, 22 had measurable di sease, and 9 radiographic responses (50% or more decrease in enhancing tumors) were observed in these patients. Carboplatin and etoposide wi th blood-brain barrier disruption is an active regimen in the treatmen t of malignant astrocytomas and has shown dramatic responses in primit ive neuroectodermal tumors and CNS lymphoma. Additionally, the durabil ity of responses in patients with disseminated CNS germ cell tumors is encouraging. However, such therapy is associated with unexpected high -frequency hearing loss; even so, on the basis of the favorable respon ses in patients with primitive neuroectodermal tumors, germ cell tumor s, and lymphomas, the study of this regimen for those tumors is being extended in a multiinstitutional trial that also includes cytoxan to f urther evaluate the potential enhanced drug delivery.