OBJECTIVE: We report the safety and feasibility of using convection-enhanced delivery to administer Cotara (Peregrine Pharmaceuticals, Inc., Tustin, CA), a novel radioimmunotherapeutic agent, to patients with malignant glioma.
METHODS: Between April 1998 and November 2002, 51 patients with histologically confirmed malignant glioma received Cotara by convection-enhanced delivery. Most patients (88%) were treated with Cotara targeting tumor volume-dependent, single or multiple administrations of activity ranging from 0.5 to 3.0 mCi/cm3 of baseline clinical target volume. Two weeks after infusion, single-photon emission computed tomographic imaging determined the spatial distribution of Cotara. Patients were followed for as long as 41 months (average follow-up, 5 mo). Safety was evaluated on the basis of incidence of procedure-related, neurological, and systemic adverse events. Feasibility was evaluated in a subset of patients on the basis of the correlation between the prescribed activity and the actual activity administered to the targeted region.
RESULTS: Fifty-one patients, 37 with recurrent glioblastoma multiforme, 8 with newly diagnosed glioblastoma multiforme, and 6 with recurrent anaplastic astrocytomas, were treated. Average tumor volume was 36 ± 27.6 cm3 (range, 5–168 cm3). Of the 67 infusions, 13 (19%), 52 (78%), and 2 (3%) delivered less than 90%, 100 ± 10%, and more than 110%, respectively, of the prescribed administered activity to the targeted region. Treatment-emergent, drug-related central nervous system adverse events included brain edema (16%), hemiparesis (14%), and headache (14%). Systemic adverse events were mild. Several patients had objective responses to Cotara.
CONCLUSION: The majority of Cotara infusions delivered between 90 and 110% of the prescribed administered activity to the targeted region. This method of administration has an acceptable safety profile compared with literature reports of other therapeutics delivered by convection-enhanced delivery.
Department of Neurological Surgery, Medical University of South Carolina, Charleston, South Carolina (Patel)
Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital, Phoenix, Arizona (Shapiro)
Neurosurgical Oncology, Temple University School of Medicine, Philadelphia, Pennsylvania (Laske)
Department of Neurological Surgery, University of Utah Medical Center, Salt Lake City, Utah (Jensen)
Neurosurgery, Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina (Asher)
Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (Wessels)
Clinical Affairs, Peregrine Pharmaceuticals, Inc., Tustin, California (Carpenter, Shan)
Reprint requests: William R. Shapiro, M.D., Barrow Neurological Institute, St. Joseph’s Hospital, Division of Neurology, 350 West Thomas Road, Phoenix, AZ 85013. Email: firstname.lastname@example.org
Received, June 21, 2004.
Accepted, January 13, 2005.