Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse

Détails

ID Serval
serval:BIB_5D861A4795A6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
Périodique
Annals of Oncology
Auteur(s)
Brada  M., Hoang-Xuan  K., Rampling  R., Dietrich  P. Y., Dirix  L. Y., Macdonald  D., Heimans  J. J., Zonnenberg  B. A., Bravo-Marques  J. M., Henriksson  R., Stupp  R., Yue  N., Bruner  J., Dugan  M., Rao  S., Zaknoen  S.
ISSN
0923-7534 (Print)
Statut éditorial
Publié
Date de publication
02/2001
Volume
12
Numéro
2
Pages
259-66
Notes
Clinical Trial
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't --- Old month value: Feb
Résumé
BACKGROUND: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life. PATIENTS AND METHODS: We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) > or = 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naive patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle. Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle. RESULTS: The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria. Secondary endpoints included radiological response and Health-related Quality of Life (HQL). Progression-free survival at six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible-histology population. Median progression-free survival and median overall survival were 2.1 months and 5.4 months, respectively. The six-month survival rate was 46%. The objective response rate (complete response and partial response) determined by independent central review of gadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible-histology populations, with an additional 43% and 45% of patients, respectively, having stable disease (SD). Objectively assessed response and maintenance of a progression-free status were both associated with HQL benefits (characterized by improvements over baseline in HQL domains). Temozolomide had an acceptable safety profile, with only 9% of therapy cycles requiring a dose reduction due to thrombocytopenia. There was no evidence of cumulative hematologic toxicity. CONCLUSIONS: Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM. The use of this drug should be explored further in an adjuvant setting and in combination with other agents.
Mots-clé
Adult Aged Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use Brain Neoplasms/*drug therapy/pathology Dacarbazine/adverse effects/analogs & derivatives/*therapeutic use Disease-Free Survival Female Glioblastoma/*drug therapy/pathology Humans Male Middle Aged Neoplasm Recurrence, Local/drug therapy/pathology Prognosis Quality of Life
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 9:39
Dernière modification de la notice
20/08/2019 15:15
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