levoleucovorin and Glioblastoma

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

Glioblastoma multiforme (GBM) invades beyond enhancing boundaries, and tumor cells are believed to exist in edematous peritumoral regions. We hypothesize that the concomitant treatment of both enhancing and FLAIR abnormalities on MRI by fractionated radiosurgery (FRS) would reduce local and regional recurrence. The purpose of this study was to demonstrate patterns of failure after FRS with simultaneous differential doses to two different target volumes of contrast enhancing lesions with/without FLAIR abnormality in recurrent GBM. Fifty-three patients with recurrent GBM were treated with FRS between 2008 and 2012. FRS was offered for the patients who had progressive tumors after the initial surgical resection followed by chemoradiation, and second-line chemotherapy. Radiosurgery Regimen A was 32 Gy (8 Gy × 4 treatments) to the contrast enhancing lesion only. Regimen B was 32 Gy (8 Gy × 4) to the contrast enhancing lesion and 24 Gy (6 Gy × 4) to the FLAIR abnormality delivered concomitantly. The study endpoint was radiographic failure on MRI at 2 months after FRS. Median survival after FRS was 7.5 months, and median progression-free survival after FRS was 4 months. Overall 82.4 % (42/51 lesions) recurred during follow-up. The local and regional failure rate was significantly lower in Regimen B (52 %) than in Regimen A (86.7 %) (p = 0.003). No sign of tumor progression in 10 % of Regimen A versus 28.6 % of Regimen B was shown during followup (p = 0.04). Instead, distant failure rate was higher in Regimen B. In conclusions, FRS was found to be a safe and effective salvage therapy for recurrent GBM. FRS to both contrast enhancing and FLAIR abnormalities appeared to improve local tumor control, and reduce regional tumor progression.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Glioblastoma; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Postoperative Complications; Radiosurgery; Retrospective Studies; Treatment Outcome

A five-year-old girl developed acute myelomonocytic leukemia after fifteen months of intensive chemotherapy and irradiation for glioblastoma multiforme. The leukemia became manifest while the patient was in a remarkable remission brought about by treatment with high-dose methotrexate with citrovorum rescue. This is the first reported association of these disorders in the same patient. It is possible that the leukemia was induced by the treatment, since both radiation and the chemotherapeutic drugs used have been shown to be leukemogenic in some circumstances. The patient developed leukemia in a setting of relatively normal peripheral blood counts, having had very little myelosuppression from her treatment.

Topics: Antineoplastic Agents; Brain Neoplasms; Carmustine; Child, Preschool; Dexamethasone; Drug Therapy, Combination; Female; Glioblastoma; Humans; Leucovorin; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Methotrexate; Neoplasms, Multiple Primary

Topics: Aged; Astrocytoma; Brain Neoplasms; Catheterization; Craniotomy; Female; Glioblastoma; Headache; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Unconsciousness