levoleucovorin and Glioma

Fourteen patients with malignant gliomas were entered on a phase II study of 5-fluorouracil 300-370 mg/m2 plus folinic acid 200 mg/m2 x 5 days q4 weeks. To be eligible, patients could not have received more than 1 prior chemotherapy regimen. A single patient with a recurrent oligodendroglioma responded. Toxicity (predominantly stomatitis, diarrhea, and granulocytopenia) was tolerable and was similar to that seen in studies of 5-fluorouracil plus folinic acid in other tumor types. This regimen has minimal activity in recurrent malignant gliomas.

Topics: Adult; Aged; Astrocytoma; Brain Neoplasms; Female; Fluorouracil; Glioblastoma; Glioma; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged

The reduced bioavailability of chemotherapeutic agents is one of the reasons that explains the limited efficacy of adjuvant chemotherapy in high grade glioma patients. We report how even the results of high dose sequential chemotherapy can be influenced by antiepileptic drugs.

Topics: Adult; Anticonvulsants; Biological Availability; Brain Neoplasms; Breast Neoplasms; Chemotherapy, Adjuvant; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Glioma; Humans; Leucovorin; Methotrexate

Intra-arterial high dose methotrexate (MTX) infusion therapy for ACNU resistant recurrent gliomas was reported. MTX was administered 16 times to 6 patients. In all cases, 20% mannitol was infused to produce a reversible osmotic blood brain barrier disruption. Dosage of infused MTX was 1,000-2,000 mg per an artery. One case revealed a complete response on CT. Another case showed an intratumoral necrosis. Intra-arterial high dose MTX infusion yielded high arterial and cerebrospinal fluid concentration of MTX. No critical complications were experienced. Dosage of MTX, an interval between the therapies and proper timing to start leucovorin rescue will be discussed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Drug Evaluation; Female; Glioma; Humans; Infusions, Intra-Arterial; Leucovorin; Male; Mannitol; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Remission Induction

Chemotherapeutic drug delivery can be enhanced by administering drugs into the internal carotid or vertebral artery circulation after osmotic opening of the blood-brain barrier (BBB). As evidence of the clinical implications of this technique, radiographic documentation of central nervous system (CNS) tumor regression was observed in three patients concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic blood-brain barrier opening. These three patients, one with metastatic carcinoma of the breast, one with glioblastoma, and one with primary CNS lymphoma, highlight the importance of drug delivery to CNS malignancies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood-Brain Barrier; Brain Neoplasms; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Combined Modality Therapy; Cyclophosphamide; Female; Glioma; Humans; Leucovorin; Lymphoma; Male; Mannitol; Methotrexate; Procarbazine; Tomography, X-Ray Computed; Water-Electrolyte Balance

Eleven patients with brain tumors recurrent after surgery and radiation therapy were treated with high-dose methotrexate (MTX) (300-500 mg/kg) with citrovorum factor rescue (CFR). MTX was given as an iv infusion over 4 hours followed 2 hours later by oral CFR (10 mg every 6 hours X 12). MTX levels were measured in the serum, lumbar cerebrospinal fluid (CSF), and ventricular CSF at 0, 4, 12, 24, 48, and 72 hours from the start of the MTX infusion. MTX concentrations of greater than 10(-6) M were measured in the CSF over a period of 24 hours after the iv infusion. Peak CSF concentrations reached were greater than 10(-5) M. After the response to high-dose MTX with CFR was evaluated, vincristine (1.5 mg/m2) and a nitrosourea (methyl-CCNU or BCNU) were added to this treatment regimen. Two of four patients with recurrent pontine glioma and five of seven patients with recurrent medulloblastoma had favorable objective responses to treatment. It is suggested that high-dose MTX with CFR be cautiously considered for the primary treatment of intracranial neoplasms in children with the hope of increasing the cure rate for children with malignant brain tumors.

Topics: Brain Neoplasms; Child; Child, Preschool; Drug Therapy, Combination; Female; Glioma; Humans; Leucovorin; Male; Medulloblastoma; Methotrexate; Neoplasm Recurrence, Local; Pons

Topics: Adolescent; Adult; Brain Neoplasms; Drug Therapy, Combination; Female; Glioma; Humans; Infusions, Parenteral; Leucovorin; Male; Methotrexate; Middle Aged; Nervous System

Topics: Administration, Oral; Brain Neoplasms; Calcium; Child; Drug Evaluation; Glioma; Humans; Infusions, Parenteral; Leucovorin; Male; Methotrexate; Neoplasm Recurrence, Local; Pons; Remission, Spontaneous

Topics: Adenoma, Chromophobe; Adolescent; Adult; Aged; Brain Neoplasms; Child; Child, Preschool; Cobalt Isotopes; Female; Floxuridine; Folic Acid; Glioma; Humans; Infusions, Parenteral; Leucovorin; Male; Methotrexate; Middle Aged; Radioisotope Teletherapy

Topics: Aphasia; Brain Neoplasms; Carotid Arteries; Cerebral Angiography; Drug Therapy; Glioma; Humans; Infusions, Intra-Arterial; Leucovorin; Methotrexate; Necrosis; Paralysis; Parietal Lobe; Surgical Procedures, Operative; Temporal Lobe