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.
BACKGROUND
Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-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).


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/m(2) 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.


CONCLUSIONS
Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GBM.
van den Bent
M J
MJ
Department of Neuro-Oncology, Daniel den Hoed Cancer Center/Erasmus University Medical Center, Rotterdam, The Netherlands. m.vandenbent@erasmusmc.nl
Grisold
W
W
Frappaz
D
D
Stupp
R
R
Desir
J P
JP
Lesimple
T
T
Dittrich
C
C
de Jonge
M J A
MJ
Brandes
A
A
Frenay
M
M
Carpentier
A F
AF
Chollet
P
P
Oliveira
J
J
Baron
B
B
Lacombe
D
D
Schuessler
M
M
Fumoleau
P
P
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D005947:Glucose / Q000031:analogs & derivatives; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010752:Phosphoramide Mustards / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D010752:Phosphoramide Mustards; C092028:beta-D-glucosylisophosphoramide mustard; D005947:Glucose; D007069:Ifosfamide