Maintenance therapy with 13-cis retinoid acid in high-grade glioma at complete response after first-line multimodal therapy--a phase-II study.
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.


CONCLUSIONS
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.
Wismeth
Caecilia
C
Department of Neurology, University of Regensburg, Regensburg, Germany. caecilia.wismeth@medbo.de
Hau
Peter
P
Fabel
Klaus
K
Baumgart
Ulrike
U
Hirschmann
Birgit
B
Koch
Horst
H
Jauch
Tanja
T
Grauer
Oliver
O
Drechsel
Lisa
L
Brawanski
Alexander
A
Bogdahn
Ulrich
U
Steinbrecher
Andreas
A
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000209:etiology*; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015474:Isotretinoin