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Maintenance Therapy with 13-cis Retinoid Acid
in High-Grade Glioma at Complete Response After First-Line Multimodal Therapy –
A Phase-II Study
Caecilia Wismeth, Peter Hau, Klaus Fabel, Ulrike
Baumgart, Birgit Hirschmann, Horst Koch, Tanja Jauch, Oliver
Grauer, Lisa Drechsel, Alexander Brawanski, Ulrich Bogdahn, Andreas Steinbrecher
Department
of Neurology, University of Regensburg, Regensburg, Germany (C.W., P.H., U.B.,
B.H., H.K., T.J., O.G., L.D., A.B., U.B., A.S.); Department of Neurosurgery,
Stanford University Medical Center, Stanford, CA, USA (K.F.).
Background.
Approximately 5% of patients with malignant glioma achieve complete response
(CR) after first-line combined modality treatment.
Although these patients will invariably suffer from tumor recurrence, they
usually do not receive any further treatment to maintain remission.
According to in vitro and in vivo clinical studies, 13-cis
retinoic acid (cRA) may be a promising agent for maintenance therapy in these
patients.
Objective.
We initiated a clinical study to evaluate the feasibility and toxicity of
high-dose cRA as maintenance therapy in patients with high-grade glioma in
complete remission after first-line multimodal treatment.
Methods. A prospective single-arm phase-II study in
patients with CR after combined first-line therapy (neurosurgery, radio- and
chemotherapy) was performed.
Patients were treated with cRA at 60 mg/m2
BS from day 1 to 21 in four-weekly cycles with a dose escalation of up to 100
mg/m2 BS until tumor recurrence.
Clinical controls were performed every 4 weeks, magnetic resonance imaging every
8 weeks.
Results. Twenty-three patients (10, grade IV; 13, grade
III) were evaluable using an intention-to-treat analysis.
Treatment was well tolerated for up to 149 weeks with moderate dermatological
symptoms in all patients.
No grade 4 toxicities were observed.
Median time to progression was 41 weeks, median overall survival 74 weeks after
inclusion in the protocol.
Discussion.
There is an urgent need for strategies maintaining remission in patients with
malignant glioma.
Maintenance therapy with high-dose cRA is feasible and well tolerated over long
periods of time.
A controlled clinical trial to test the efficacy of cRA as a maintenance
treatment in malignant glioma is warranted.
Keywords: anaplastic glioma, 13-cis retinoic acid, glioblastoma,
high-grade glioma, maintenance therapy, retinoids
Copyright
©
2004 Kluwer Academic Publishers.
All rights reserved
Source:
doi:10.1023/B:NEON.0000024748.26608.2f
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