title: All-trans retinoic acid in relapsing malignant gliomas: clinical and radiological stabilization associated with the appearance of intratumoral calcifications.
abstract: OBJECTIVE
  To evaluate the therapeutic effect of all-trans retinoic acid (ATRA) with and without cytosine arabinoside in relapsing malignant gliomas.
  
  
  METHODS
  9 patients (8 male, 1 female, age 53.9 +/- 11.2) with relapsing malignant gliomas (grade IV:6; grade III:3) were treated by ATRA 1 to 21 months after the end of their initial treatment. ATRA was given unceasingly during 2 to 17 months at 90 mg/d. In 6 patients it was associated to cytosine arabinoside (4 g/course, 1 to 9 courses every 4 weeks).
  
  
  RESULTS
  4 non-responder patients died 2.5 to 4 months after starting therapy. One patient who had been reoperated before receiving ATRA and cytosine arabinoside (5 course) had no sign of tumor recurrence after 17 months of treatment. In 4 responder patients (2 glioblastoma and 2 anaplastic astrocytoma) a clinical and radiological stabilization (time to progression) during 9 +/- 2.5 months was observed. This stabilization was associated in 3 of them with the appearance of intra tumoral calcifications visualized on repeated CT scans and confirmed in one patient by post-mortem examination. All of them had received cytosine arabinoside (1 to 9 courses) with ATRA; however small calcifications were also observed in one non-responder patient who did not receive aracytine.
  
  
  CONCLUSIONS
  These results suggest: a) a therapeutic effect of ATRA in combination with cytosine arabinoside in patients with relapsing malignant gliomas b) that intratumoral calcifications are related to the effects of ATRA on differentiation and/or on endothelial t-PA production and that these effects explain the tumor progression arrest in responder patients. The transient efficiency is probably related to the pharmacokinetics of ATRA or to changes of cellular mechanisms that modulate the cell response to the drug and is a critical issue for this therapy.
authors.affiliation: Department de Neurosciences, Hôpital Henri Mondor, Créteil, France.
authors.forename: G L
authors.initials: GL
authors.lastname: Defer
authors.forename: H
authors.initials: H
authors.lastname: Adle-Biassette
authors.forename: F
authors.initials: F
authors.lastname: Ricolfi
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.forename: F J
authors.initials: FJ
authors.lastname: Authier
authors.forename: C
authors.initials: C
authors.lastname: Chomienne
authors.forename: L
authors.initials: L
authors.lastname: Degos
authors.forename: J D
authors.initials: JD
authors.lastname: Degos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002114:Calcinosis; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011859:Radiography; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D014212:Tretinoin