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Journal of Neuro-Oncology

, Volume 51, Issue 1, pp 57–66 | Cite as

Redifferentiation Therapy in Brain Tumors: Long-lasting Complete Regression of Glioblastomas and an Anaplastic Astrocytoma Under Long Term 1-alpha-hydroxycholecalciferol

  • Paul Trouillas
  • Jerome Honnorat
  • Philippe Bret
  • Anne Jouvet
  • Jean-Pierre Gerard
Article

Abstract

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 μg/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.

alfacalcidol vitamin D vitamin D receptors vitamin D analogs glioblastoma anaplastic astrocytoma 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Paul Trouillas
    • 1
  • Jerome Honnorat
    • 1
  • Philippe Bret
    • 2
  • Anne Jouvet
    • 3
  • Jean-Pierre Gerard
    • 4
  1. 1.Neurology, Neurovascular and Neuro-oncology service (Service B)France
  2. 2.Neurosurgery serviceHôpital NeurologiqueLyonFrance
  3. 3.Neuropathology serviceHôpital NeurologiqueLyonFrance
  4. 4.Radiotherapy serviceCentre Hospitalier Lyon-SudLyonFrance

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