Promising Results With Motexafin for Brain Metastases and Glioblastoma Multiforme

February 1, 2001

Results of the lead-in phase of an ongoing randomized phase III trial of motexafin (Xcytrin) in patients with brain metastases, as well as preliminary results of an ongoing phase I trial of motexafin for glioblastoma multiforme, were presented at the 42nd

Results of the lead-in phase of an ongoingrandomized phase III trial of motexafin (Xcytrin) inpatients with brain metastases, as well as preliminary results of an ongoingphase I trial of motexafin for glioblastoma multiforme, were presented at the 42nd annual meeting of the American Society for Therapeutic Radiology andOncology.

"Xcytrin appeared to improve local control in the brain,with very few patients experiencing neurologic progression, neurocognitivedeterioration, or death due to tumor progression," said Minesh Mehta, MD,associate professor and interim chair, department of human oncology, Universityof Wisconsin Medical School, and cochairman of the phase III trial. "Thefindings that radiologic responses were correlated with improved survival, andthat neurocognitive performance was an independent predictor of survival give usconfidence that the phase III trial is well designed to meet the efficacy endpoints."

Phase III Trial

In the open-label lead-in phase of the phase III trial, 25patients with brain metastases received an injection of motexafin followed bystandard whole-brain irradiation once a day for 10 days. Investigators assessedthe effect of this treatment on tumor control via several methods, includingmagnetic resonance imaging (MRI) scans to measure tumor response and a batteryof tests to evaluate neurologic and neurocognitive function.

A tumor response was seen in 68% of patients evaluable by MRI(13 out of 19), with a median reduction in tumor volume of 83%; 77% of all 25patients were free from neurologic progression. Radiologic response andneurocognitive test scores were found to correlate with survival. Mediansurvival for all 25 patients was 5 months, and only 23% of patients died as aresult of neurologic progression.

Treatment Well Tolerated

Treatment with motexafin was well tolerated with no seriousdrug-related toxicities observed (94% [236 of 250] of the planned motexafindoses were delivered). Side effects were generally reversible and relativelyminor, including temporary skin discoloration, change in urine color, nausea,hypertension, and liver enzyme abnormalities in some patients. Patients enrolledin the study had very advanced disease and were not eligible for radiosurgery.On average, each patient had 11 brain tumors. The majority of patients in thelead-in phase of the trial had advanced lung or breast cancer that had spread tothe brain.

"The lead-in data, which confirm the results of ourpreviously reported phase Ib/II study are encouraging in that they appear tosupport the coprimary efficacy end points of the phase III trial," saidMarkus Renschler, MD, senior director of clinical development at Pharmacyclics,the manufacturer of motexafin. "We and our collaborators believe this isthe most comprehensive clinical trial ever performed for this disease. Manyimportant clinical parameters are being measured, including survival, neurologicfunction, neurocognitive function, and radiologic response. We expect to capturea large amount of important clinical information from this trial."

Enrollment in the phase III trial is nearing completion at morethan 50 medical centers in the United States, Canada, and Europe. Patients arebeing randomly assigned to treatment with either standard radiation plusmotexafin or standard radiation alone. Improvement in either survival or time toneurologic progression are the coprimary end points of the trial.

Phase I Trial

Dr. Mehta also reported the interim results of the ongoing phaseI trial in patients with glioblastoma multiforme who are receiving motexafincombined with whole-brain irradiation. Researchers observed a median survivalrate of 22.8 months among the 21 patients evaluated so far.

"While preliminary, these results are encouragingconsidering the expected survival for this type of cancer is approximately 11months," said Dr. Mehta. Because the treatments have been well tolerated,dose escalation is continuing. The study is being conducted at the University ofCalifornia at Los Angeles (UCLA) Medical Center by lead investigator, JudithFord, MD, under a Cooperative Research and Development Agreement betweenPharmacyclics and the National Cancer Institute.