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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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