Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma.

Abstract

PURPOSE:

This multi-institutional phase I trial was designed to determine the maximum-tolerated dose (MTD) of cilengitide (EMD 121974) and to evaluate the use of perfusion magnetic resonance imaging (MRI) in patients with recurrent malignant glioma.

PATIENTS AND METHODS:

Patients received cilengitide twice weekly on a continuous basis. A treatment cycle was defined as 4 weeks. Treatment-related dose-limiting toxicity (DLT) was defined as any grade 3 or 4 nonhematologic toxicity or grade 4 hematologic toxicity of any duration.

RESULTS:

A total of 51 patients were enrolled in cohorts of six patients to doses of 120, 240, 360, 480, 600, 1,200, 1,800, and 2,400 mg/m2 administered as a twice weekly intravenous infusion. Three patients progressed early and were inevaluable for toxicity assessment. The DLTs observed were one thrombosis (120 mg/m2), one grade 4 joint and bone pain (480 mg/m2), one thrombocytopenia (600 mg/m2) and one anorexia, hypoglycemia, and hyponatremia (800 mg/m2). The MTD was not reached. Two patients demonstrated complete response, three patients had partial response, and four patients had stable disease. Perfusion MRI revealed a significant relationship between the change in tumor relative cerebral blood flow (rCBF) from baseline and area under the plasma concentration versus time curve after 16 weeks of therapy.

CONCLUSION:

Cilengitide is well tolerated to doses of 2,400 mg/m2, durable complete and partial responses were seen in this phase I study, and clinical response appears related to rCBF changes.

• Authors: L Burt Nabors, Tom Mikkelsen, Steven S Rosenfeld, Fred Hochberg, Narasimha S Akella, Joy D Fisher, Gretchen A Cloud, Yu Zhang, Kathryn Carson, Sabine M Wittemer, A Dimitrios Colevas, Stuart A Grossman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 13 Pg. 1651-7 (May 01 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17470857 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Snake Venoms
• Cilengitide

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Brain Neoplasms (drug therapy, pathology)
• Cohort Studies
• Glioma (drug therapy, pathology)
• Humans
• Magnetic Resonance Imaging
• Maximum Tolerated Dose
• Recurrence
• Snake Venoms (adverse effects, therapeutic use)