Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse

Citation
Wka. Yung et al., Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse, J CL ONCOL, 17(9), 1999, pp. 2762-2771
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
JOURNAL OF CLINICAL ONCOLOGY
ISSN journal
0732-183X → ACNP
Volume
17
Issue
9
Year of publication
1999
Pages
2762 - 2771
Database
ISI
SICI code
0732-183X(199909)17:9<2762:MPITOT>2.0.ZU;2-L
Abstract
Purpose: To determine the antitumor efficacy and safety profile of temozolo mide in patients with malignant astrocytoma at first relapse. Patients and Methods: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population), After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma ( AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temo-zolomide 200 mg/m(2)/d, Patients previously treated with chemotherapy received temozolomide 150 mg/ m(2)/d; the dose could be increa sed to 200 mg/m2/d in the absence of grade 3/4 toxicity. Therapy was admini stered orally on the first 5 days of a 28-day cycle. Results: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%), The median PFS wa s 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and la-month survival rates were 75% and 56%, resp ectively. The objective response rate determined by independent central rev iew of gadolinium-enhanced magnetic resonance imaging scans of the ITT popu lation was 35% (8% complete response [CRI, 27% partial response [PR]), with an additional 26% of patients with stable disease (SD), The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Ma intenance of progression-free status and objectively assessed response (CR/ PR/SD) were both associated with health-related quality-of-life (HQL) benef its. Adverse events were mild to moderate, with hematologic side effects oc curring in less than 10% of patients. Conclusion: Temozolomide demonstrated good single-agent activity, an accept able safety profile, and documented HQL benefits in patients with recurrent AA. a 1999 by American Society of Clinical Oncology.