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.

Abstract

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).

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/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.

CONCLUSION:

Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GBM.

• Authors: M J van den Bent, W Grisold, D Frappaz, R Stupp, J P Desir, T Lesimple, C Dittrich, M J A de Jonge, A Brandes, M Frenay, A F Carpentier, P Chollet, J Oliveira, B Baron, D Lacombe, M Schuessler, P Fumoleau, European Organization for Research and Treatment of Cancer New Drug Development Group, European Organization for Research and Treatment of Cancer Brain Tumor Group
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 14 Issue 12 Pg. 1732-4 (Dec 2003) ISSN: 0923-7534 [Print] England
• PMID: 14630677 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phosphoramide Mustards
• beta-D-glucosylisophosphoramide mustard
• Glucose
• Ifosfamide

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, pharmacokinetics, therapeutic use)
• Brain Neoplasms (drug therapy, pathology)
• Disease-Free Survival
• Female
• Glioblastoma (drug therapy, pathology)
• Glucose (analogs & derivatives)
• Humans
• Ifosfamide (analogs & derivatives)
• Infusions, Intravenous
• Male
• Middle Aged
• Phosphoramide Mustards (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Treatment Outcome