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Multicenter
phase II trial of temozolomide in patients with glioblastoma multiforme at first
relapse
Brada M, Hoang-Xuan K, Rampling R, Dietrich PY, Dirix LY, Macdonald D,
Heimans JJ, Zonnenberg BA, Bravo-Marques JM, Henriksson R, Stupp R, Yue N,
Bruner J, Dugan M, Rao S, Zaknoen S.
The Royal Marsden Hospital, Surrey, UK. mbrada@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 [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.
PMID: 11300335 [PubMed - indexed for
MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11300335&dopt=Abstract |
