SAN FRANCISCOMotexafin gadolinium (Xcytrin), an experimental drug that makes brain tumors more sensitive to radiation, appears to be well tolerated in adults with primary glioblastoma multiforme and children with gliomas, according to preliminary results from two phase I trials presented at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO).
Judith M. Ford, MD, PhD, assistant professor of radiation oncology, UCLA Medical Center, said that median survival for the first 24 patients in the glioblastoma study was 17.3 months (abstract 213). She also reported that imaging studies showed the drug to be present in the tumor throughout the course of treatment, but not in normal brain tissue.
Xcytrin is the first of a new class of porphyrin-like compounds called texaphyrins that are active as reduction oxidation (redox) modulators. The agent enhances radiation-induced apoptosis through caspase activation secondary to futile redox cycling.
Markus Renschler, MD, vice president of oncology clinical development for Xcytrin-developer Pharmacyclics, Inc., Sunnyvale, Calif (www.pcyc.com), said the company is proceeding with a phase II glioblastoma trial in the hope of starting a phase III trial by early next year.
Dr. Renschler told ONI that the 17.3 months median survival in the phase I study of patients with advanced glioblastoma was "provocative," since survival for these patients as reported in the literature is generally only 10 to 11 months.
Response and survival data for the pediatric study of intrinsic pontine (brainstem) gliomas are blocked until completion under the Children’s Oncology Group protocol, said Minesh Mehta, MD, of the University of Wisconsin Medical School, Madison.
He reported (abstract 243) that the trial has established that children can take Xcytrin on a 5-day-a-week dosing schedule. Sixteen children had participated in the dose-escalation trial as of May, with the fourth cohort receiving 1.9 mg/m² five times a week. A fifth cohort at 2.1 mg/m² was expected to start shortly.