Annals of Oncology 12:259-266, 2001
© 2001 European Society for Medical Oncology
research-article |
Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
1The Royal Marsden Hospital Surrey, UK
2Hôspital de la Pitiè-Salpetrière Paris. France
3Beatson Oncology Center Western Infirmary Glasgow, Scotland
4Division of Oncology, University Hospital of Geneva Geneva, Switzerland
5Laboratory of Cancer Leuven, Belgium
6The London Regional Cancer Center London, Ontario, Canada
7The Free University Hospital Amsterdam
8The Free University Hospital of Utrecht Utrecht, The Netherlands
9Centro de Lisboa de Instituto Portugues de Oncologia Lisbon, Portugal
10Norrland University Hospital Umeda, Sweden
11Centre Pluralistique d'oncologie Lausanne, Switzerland
12Johns Hopkins University Baltimore. Maryland
13The University of Texas, M.D. Anderson Cancer Center, Houston, Texas
14Schering-Plough Pharmaceuticals Kenilworth. New Jersey, USA
The Institute of Cancer Research and the Royal Marsden NHS Trust Downs Road Sutton, Surrey SM2 5PT UKmbrada{at}icr.ac.uk
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.
chemotherapy, glioblastoma multiforme, quality of life, temozolomide, tumor response
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