mitoguazone and Meningeal-Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Combinations; Drug Evaluation; Female; Humans; Leukemia, Myeloid, Acute; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Middle Aged; Mitoguazone; Prednisone; Thioguanine; Vincristine

Methylglyoxal bis(guanylhydrazone) (MGBG; NSC 32946) is currently being reevaluated for its clinical antineoplastic activity against both hematological and solid tumors. MGBG (100 to 200 mg/sq m) was administered by slow infusion over 3 hr to six patients during surgical resection of intracerebral tumors. Excised tumor tissue and plasma were assayed for MGBG by high-pressure liquid chromatography. In all cases, MGBG penetrated rapidly into brain tumor tissue. Viable tumor tissue contained greater concentrations of MBGB than did necrotic tumor tissue. In two patients with glioblastoma multiforme, MBGB concentrations in brain tumor tissue were five- to 19-fold higher than concurrent plasma samples. However, MGBG did not penetrate well into the cerebrospinal fluid of two patients with Ommaya reservoirs given i.v. MGBG (200 mg/sq m). The highest MGBG concentration in cerebrospinal fluid reached only 22% of the concurrent plasma levels. These studies suggest that MGBG may be a useful agent in the treatment of intracerebral tumors but may not be effective against meningeal leukemia and meningeal carcinomatosis.

Topics: Blood-Brain Barrier; Brain Neoplasms; Guanidines; Humans; Meningeal Neoplasms; Mitoguazone