Fulltext

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

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.

In: Annals of Oncology, 2001, vol. 12, no. 2, p. 259-266

Ajouter à la liste personnelle
    Titre
    • Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
    Auteur
    • Brada, M.. The Royal Marsden Hospital Surrey, UK
    • Hoang-Xuan, K.. Hôspital de la Pitiè-Salpetrière Paris. France
    • Rampling, R.. Beatson Oncology Center Western Infirmary Glasgow, Scotland
    • Dietrich, P-Y. Division of Oncology, University Hospital of Geneva Geneva, Switzerland
    • Dirix, L. Y.. Laboratory of Cancer Leuven, Belgium
    • Macdonald, D.. The London Regional Cancer Center London, Ontario, Canada
    • Heimans, J. J.. The Free University Hospital Amsterdam
    • Zonnenberg, B. A.. The Free University Hospital of Utrecht Utrecht, The Netherlands
    • Bravo-Marques, J. M.. Centro de Lisboa de Instituto Portugues de Oncologia Lisbon, Portugal
    • Henriksson, R.. Norrland University Hospital Umeda, Sweden
    • Stupp, R.. Centre Pluralistique d'oncologie Lausanne, Switzerland
    • Yue, N.. Johns Hopkins University Baltimore. Maryland
    • Bruner, J.. The University of Texas, M.D. Anderson Cancer Center, Houston, Texas
    • Dugan, M.. Schering-Plough Pharmaceuticals Kenilworth. New Jersey, USA
    • Rao, S.. Schering-Plough Pharmaceuticals Kenilworth. New Jersey, USA
    • Zaknoen, S.. Schering-Plough Pharmaceuticals Kenilworth. New Jersey, USA
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Annals of Oncology, 2001, vol. 12, no. 2, p. 259-266. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:304252
    Summary
    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 [ITI] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) ≥ 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day2/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%;A 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