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All-trans retinoic acid in relapsing malignant gliomas: clinical and radiological stabilization associated with the appearance of intratumoral calcifications

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Abstract

(1) Purpose: To evaluate the therapeutic effect ofall-trans retinoic acid (ATRA) with and without cytosinearabinoside in relapsing malignant gliomas.(2) Patients and methods: 9 patients (8 male,1 female, age 53.9 ± 11.2) with relapsingmalignant gliomas (grade IV:6; grade III:3) were treatedby ATRA 1 to 21 months after theend of their initial treatment. ATRA was givenunceasingly during 2 to 17 months at 90mg/d. In 6 patients it was associated tocytosine arabinoside (4 g/course, 1 to 9 coursesevery 4 weeks).(3) Results: 4 non-responder patients died 2.5 to4 months after starting therapy. One patient whohad been reoperated before receiving ATRA and cytosinearabinoside (5 courses) had no sign of tumorrecurrence after 17 months of treatment. In 4responder patients (2 glioblastoma and 2 anaplastic astrocytoma)a clinical and radiological stabilization (time to progression)during 9 ± 2.5 months was observed. Thisstabilization was associated in 3 of them withthe appearance of intra tumoral calcifications visualized onrepeated CT scans and confirmed in one patientby post-mortem examination. All of them had receivedcytosine arabinoside (1 to 9 courses) with ATRA;however small calcifications were also observed in onenon-responder patient who did not receive aracytine.(4) Conclusion: These results suggest: a) a therapeuticeffect of ATRA in combination with cytosine arabinosidein patients with relapsing malignant gliomas b) thatintratumoral calcifications are related to the effects ofATRA on differentiation and/or on endothelial t-PA productionand that these effects explain the tumor progressionarrest in responder patients. The transient efficiency isprobably related to the pharmacokinetics of ATRA orto changes of cellular mechanisms that modulate thecell response to the drug and is acritical issue for this therapy.

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Authors and Affiliations

  1. Départment de Neurosciences, Hôpital Henri Mondor, Créteil, France

    Gilles-Louis Defer, Homa Adle-Biassette, Frédéric Ricolfi, Laurent Martin, François-Jérome Authier & Jean-Denis Degos

  2. Laboratoire de Biologie Cellulaire, Centre Hayem, Hôpital Saint-Louis, Paris, France

    Christine Chomienne & Laurent Degos

  3. Service de Neurologie Dejerine, CHU Côte de Nacre, Caen, France

    Gilles-Louis Defer

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  1. Gilles-Louis Defer
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Defer, GL., Adle-Biassette, H., Ricolfi, F. et al. All-trans retinoic acid in relapsing malignant gliomas: clinical and radiological stabilization associated with the appearance of intratumoral calcifications. J Neurooncol 34, 169–177 (1997). https://doi.org/10.1023/A:1005701507111

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