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European
Organization for Research and Treatment of Cancer (EORTC) open label phase II
study on glufosfamide administered as a 60-minute infusion every 3 weeks in
recurrent glioblastoma multiforme
M.
J. van den Bent1, W. Grisold2,
D. Frappaz3, R. Stupp4,
J. P. Desir5, T. Lesimple6,
C. Dittrich2, M. J. A. de Jonge1,
A. Brandes7, M. Frenay8,
A. F. Carpentier9, P. Chollet10,
J. Oliveira11, B. Baron12,
D. Lacombe12, M. Schuessler13
and P. Fumoleau14
1
Daniel den Hoed Cancer Center/Erasmus University Medical Center, Rotterdam, The
Netherlands; 2 LBI-ACR Vienna and Kaiser Franz Josef Spital, Vienna,
Austria; 3 Centre Léon Bérard, Lyon, France; 4 Centre
Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 5 Centre
Georges-François-Leclerc, Dijon; 6 Centre Eugène Marquis, Rennes,
France; 7 Medical Oncology Department University Hospital-Padova,
Padova, Italy; 8 Centre Lacassagne, Nice; 9 CHU Pitié-Salpétrière,
Paris; 10 Centre Jean Perrin, Clermont-Ferrand, France; 11
IPO Francisco Gentil-Centro de Lisboa, Portugal; 12 EORTC Data
Center, Brussels, Belgium; 13 Baxter Oncology GmbH, Frankfurt/Main,
Germany; 14 Centre René Gauducheau, Nantes-St Herblain, France.
Received 23 April 2003; revised 17 June 2003; accepted 12 August 2003.
Background. Glufosfamide
is a new alkylating agent in which the active metabolite of
isophosphoramide mustard is covalently linked to ß-D-glucose to target the glucose transporter system and increase
intracellular uptake in tumor cells.
We investigated this drug in a multicenter prospective phase II trial
in recurrent glioblastoma multiforme (GBM).
Patients and methods.
Eligible patients
had recurrent GBM following surgery, radiotherapy and no more than
one prior line of chemotherapy.
Patients were treated with glufosfamide 5000 mg/m2
administered as a 1-h intravenous infusion.
Treatment success was defined as patients with either an objective
response according to Macdonald’s criteria or 6 months
progression-free survival.
Toxicity was assessed with the Common Toxicity Criteria (CTC) version
2.0.
Results. Thirty-one
eligible patients were included.
Toxicity was modest, the main clinically relevant toxicities being
leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in
three patients).
No responses were observed; one patient (3%; 95% confidence interval
0 to 17%) was free from progression at 6 months.
Pharmacokinetic analysis showed a 15% decrease in area under the
curve and glufosfamide clearance in patients treated with
enzyme-inducing antiepileptic drugs, but no effect of these drugs on
maximum concentration and plasma half-life.
Conclusion. Glufosfamide
did not show significant clinical antitumor activity in patients with
recurrent GBM.
Key words: chemotherapy,
glioblastoma multiforme, glufosfamide, recurrent
© 2003
European
Society for Medical Oncology
Source: http://annonc.oupjournals.org/cgi/content/abstract/14/12/1732?etoc |
