PURPOSE: Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas. PATIENTS AND METHODS: Patients with glioblastomas and anaplastic astrocytomas were enrolled in a phase II trial involving surgery or biopsy, radiotherapy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol at the daily dose of 0.04 microg/kg. MRI took place every 6 months. RESULTS: Eleven patients were included and completed the study. The series involved 10 glioblastomas and 1 anaplastic astrocytoma. Three patients out of 11 patients (27%), 2 glioblastomas and 1 astrocytoma grade III, exhibited a particular response, consisting in the progressive regression of the radiological lesion, with a decrease of the gadolinium-enhanced area. Simultaneously, the patients showed a complete clinical remission, observed respectively for 7, 5 and 4 years. In the series of 10 patients with glioblastomas, 2 cases showed this response; after 4 years, 2 of 10 patients with glioblastomas (20%) were alive; the median survival time is 21 months. Normal or subnormal calcemia was observed, at the dose proposed, so that no interruption of the drug was necessary. CONCLUSIONS: Alfacalcidol, an in vitro agent of redifferentiation, is safe and seems able to induce in some patients, in synergy with classical surgery-radiotherapy-chemotherapy treatments, a particular progressive and durable regression of the tumor. The responders might represent about 20% of malignant gliomas.
PURPOSE: Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas. PATIENTS AND METHODS: Patients with glioblastomas and anaplastic astrocytomas were enrolled in a phase II trial involving surgery or biopsy, radiotherapy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol at the daily dose of 0.04 microg/kg. MRI took place every 6 months. RESULTS: Eleven patients were included and completed the study. The series involved 10 glioblastomas and 1 anaplastic astrocytoma. Three patients out of 11 patients (27%), 2 glioblastomas and 1 astrocytoma grade III, exhibited a particular response, consisting in the progressive regression of the radiological lesion, with a decrease of the gadolinium-enhanced area. Simultaneously, the patients showed a complete clinical remission, observed respectively for 7, 5 and 4 years. In the series of 10 patients with glioblastomas, 2 cases showed this response; after 4 years, 2 of 10 patients with glioblastomas (20%) were alive; the median survival time is 21 months. Normal or subnormal calcemia was observed, at the dose proposed, so that no interruption of the drug was necessary. CONCLUSIONS:Alfacalcidol, an in vitro agent of redifferentiation, is safe and seems able to induce in some patients, in synergy with classical surgery-radiotherapy-chemotherapy treatments, a particular progressive and durable regression of the tumor. The responders might represent about 20% of malignant gliomas.
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Authors: P A Forsyth; P J Kelly; T L Cascino; B W Scheithauer; E G Shaw; R P Dinapoli; E J Atkinson Journal: J Neurosurg Date: 1995-03 Impact factor: 5.115
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