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.
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.
Authors: Paul Kleihues; David N Louis; Bernd W Scheithauer; Lucy B Rorke; Guido Reifenberger; Peter C Burger; Webster K Cavenee Journal: J Neuropathol Exp Neurol Date: 2002-03 Impact factor: 3.685
Authors: Lakshmi Nayak; Katherine S Panageas; Anne S Reiner; Jason T Huse; Elena Pentsova; Stephanie G Braunthal; Lauren E Abrey; Lisa M DeAngelis; Andrew B Lassman Journal: J Neurooncol Date: 2015-04-29 Impact factor: 4.130
Authors: Oliver Grauer; Christina Pascher; Christian Hartmann; Florian Zeman; Michael Weller; Martin Proescholdt; Alexander Brawanski; Thorsten Pietsch; Wolfgang Wick; Ulrich Bogdahn; Peter Hau Journal: J Neurooncol Date: 2011-03-04 Impact factor: 4.130
Authors: Jennifer L Clarke; Fabio M Iwamoto; Joohee Sul; Katherine Panageas; Andrew B Lassman; Lisa M DeAngelis; Adília Hormigo; Craig P Nolan; Igor Gavrilovic; Sasan Karimi; Lauren E Abrey Journal: J Clin Oncol Date: 2009-06-08 Impact factor: 44.544
Authors: M W Pitz; M Lipson; B Hosseini; P Lambert; K Guilbert; D Lister; G Schroeder; K Jones; C Mihalicioiu; D D Eisenstat Journal: Curr Oncol Date: 2012-12 Impact factor: 3.677