[MOL] Promising results for brain mets..... [01219] Medicine On Line

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[MOL] Promising results for brain mets.....

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Title: ASTRO: Promising Results From Xcytrin (Motexafin) For Brain Metastases

BOSTON, MA -- October 26, 2000 -- Pharmacyclics, Inc. reported results from the lead-in phase of its ongoing randomized Phase III clinical trial of XcytrinŽ (motexafin gadolinium) Injection, for the treatment of cancer patients with brain metastases, i.e., tumors that have spread to the brain from another part of the body.

The company also reported promising preliminary results from an ongoing Phase I safety trial of Xcytrin for treatment of glioblastoma multiforme (i.e., primary brain tumors). These results were presented here at the 42nd Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO).

"Xcytrin appeared to improve local control in the brain, with very few patients experiencing neurologic progression, neurocognitive deterioration or death due to tumor progression," said Minesh Mehta, M.D., associate professor and interim chair, Department of Human Oncology, University of Wisconsin Medical School, and co-chairman of the Phase III trial. "The findings that radiologic responses were correlated with improved survival, and that neurocognitive performance was an independent predictor of survival gives us confidence that the Phase III trial is well designed to meet the efficacy endpoints."

Twenty-five patients with brain metastases were evaluated in the open-label lead-in phase of the trial, which was performed to validate the design of the ongoing prospective randomized international multi-center trial. These patients received an injection of Xcytrin followed by standard whole brain radiation treatment once a day for 10 days. Investigators assessed the effects of this treatment on tumor control in the brain using several methods, including magnetic resonance imaging (MRI) scans to measure tumor response and a battery of tests to evaluate neurologic and neurocognitive function.

Tumor response, defined as at least a 65 percent reduction in tumor volume measured by MRI, was seen in 68 percent of patients evaluable by MRI scans (13 out of 19), with a median reduction in tumor volume of 83 percent. Seventy-seven percent of all 25 patients were free from neurologic progression. Neurologic progression is based on an evaluation of neurologic signs and symptoms, neurocognitive test scores and MRI results, all of which were assessed by an independent endpoint review committee.

Radiologic response and neurocognitive test scores were found to correlate with survival. Median survival for all 25 patients was five months; only 23 percent of patients died with neurologic progression.

Treatment with Xcytrin was well tolerated with no serious drug-related toxicities observed. Ninety-four percent (236 out of 250) of the planned Xcytrin doses were delivered. Side effects associated with the drug were generally reversible and relatively minor, including temporary skin discoloration, change in urine color, nausea, hypertension and liver enzyme abnormalities in some patients.

The patients enrolled in 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 the lead-in phase of the trial had advanced lung or breast cancer that had spread to the brain.

"The lead-in data, which confirm the results of our previously reported Phase Ib/II study, are encouraging in that they appear to support the co-primary efficacy endpoints of the Phase III trial," said Markus Renschler, M.D., Pharmacyclics' senior director of clinical development. "We and our collaborators believe this is the most comprehensive clinical trial ever performed for this disease. Many important clinical parameters are being measured, including survival, neurologic function, neurocognitive function and radiologic response. We expect to capture a large amount of important clinical information from this trial."

Patient enrollment in the Phase III trial is nearing completion at more than 50 medical centers in the United States, Canada and Europe. Patients are being randomly assigned to either treatment with standard radiation plus Xcytrin or standard radiation alone. Improvement in either survival or time to neurologic progression are the co-primary endpoints of the Phase III trial, which, if met, would make the drug approvable.

During his ASTRO presentation, Dr. Dr. Mehta also reported interim results of an ongoing Phase I safety trial in patients with glioblastoma multiforme who are receiving Xcytrin combined with whole brain radiation treatment. Researchers have observed a median survival rate of 22.8 months among the 21 patients evaluated so far.

"While preliminary, these results are encouraging considering the expected survival for this type of cancer is approximately 11 months," said Dr. Mehta. Because the treatments have been well tolerated, dose escalation is continuing. The study is being conducted at the UCLA Medical Center in Los Angeles by lead investigator, Judith Ford, M.D., under a Cooperative Research and Development Agreement between Pharmacyclics and the National Cancer Institute.

Xcytrin Injection is a novel drug that augments the activity of radiation via a unique mechanism of action. While radiation therapy alone has been effective at treating cancer patients, it has many limitations, including dose-limiting toxicity to normal surrounding structures. Preclinical and clinical data indicate that Xcytrin, after repeated injections, accumulates selectively in tumors and increases the vulnerability of cancer cells to the damaging effects of radiation or chemotherapy without increasing damage to surrounding healthy cells.

Brain metastases is one of the most common conditions treated with radiation therapy. There are about 170,000 cases per year and the incidence is increasing. The most common causes of brain metastases are lung and breast cancer. Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in most cases, death.

Patients with brain metastases usually suffer serious deterioration of neurocognitive function such as loss of short-term memory, compromised verbal skills and fine motor coordination, and reduction in cognitive performance. Most patients with brain metastases have multiple lesions and are not candidates for surgical resection or radiosurgery. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain.

There are about 17,000 new cases of primary brain and nervous system tumors each year in the U.S. and more than 13,000 deaths occur from these types of malignancies.

Related Link: Pharmacyclics, Inc.

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