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Redifferentiation
therapy in brain tumors: long-lasting complete regression of glioblastomas and
an anaplastic astrocytoma under long term 1-alpha-hydroxycholecalciferol
Trouillas
P, Honnorat J, Bret P, Jouvet A, Gerard JP
Neurology
service, H pital Neurologique, Lyon, France.
paul.trouillas@chu-lyon.fr
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.
PMID:
11349882 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11349882&dopt=Abstract
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