Study Shows Promising New Drug May Improve Treatment of Cancer That Spreads To the Brain

Motexafin Gadolinium Appears to Increase Tumor Response Rate and Reduce Death

Due to Tumor Progression in Patients with Brain Metastases



Apr 02, 2001, 01:00 ET from University of Wisconsin Comprehensive Cancer Center

    MADISON, Wis., April 2 /PRNewswire/ -- A promising new approach to
 treating the more than 170,000 cancer patients in the U.S. whose cancer
 spreads from another part of their body to their brain each year may increase
 tumor response rates and reduce progression of the disease, according to a
 study published in this week's Journal of Clinical Oncology.
     The multi-center Phase Ib/II clinical trial of the investigational agent,
 motexafin gadolinium (Xcytrin(R) Injection,
 Pharmacyclics, Inc.; (Nasdaq: PCYC), Sunnyvale, Calif.), administered in
 combination with standard whole brain radiation therapy, showed the treatment
 increased local tumor control, as evidenced by a high tumor response rate
 (i.e., significant tumor shrinkage) and low rate of death due to tumor
 progression in the brain.
     "We are particularly pleased to see the high tumor response rate, which is
 nearly double what we have observed in the literature with radiation alone,"
 said Minesh Mehta, M.D., associate professor and interim chair, Department of
 Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison,
 one of the study's lead investigators.  "Based on these encouraging results,
 we conducted a large multi-center international Phase III study designed to
 measure survival and time to neurologic progression in a similar patient
 population.  Enrollment in this 428-patient trial has been completed, and we
 expect to report results by the end of this year."
     Motexafin gadolinium is the first of a new class of drugs called
 texaphyrins.  It selectively accumulates in cancer cells and disrupts cellular
 metabolism by a unique mechanism of action.  By interfering with the flow of
 energy in cancer cells, motexafin gadolinium makes the tumor more responsive
 to the effects of radiation and chemotherapy without increasing damage to
 normal tissue.
 
     Key Study Findings
     Sixty-one patients with brain metastases were enrolled in the combined
 Phase Ib/II trial.   For 10 days, daily intravenous injections of motexafin
 gadolinium were administered, followed by whole brain radiation treatment each
 day.  Thirty-nine patients were enrolled in the Phase Ib portion of the trial
 intended to determine optimal dosing and tumor localization using magnetic
 resonance imaging (MRI), and 22 patients were enrolled in the Phase II portion
 of the trial designed to assess tumor response and side effect profile.
     Eighteen Phase II patients were evaluable for tumor response based on
 follow-up MRI scans.  After a two-month follow-up, tumor response, defined as
 greater than 50 percent reduction in tumor volume, was seen in 13 of
 18 patients (72 percent), significantly higher than the 43 percent reported in
 previous studies of patients treated with standard whole brain radiation
 therapy alone.  Death due to tumor progression in the brain was just
 12 percent, compared to a rate of about 50 percent reported in previous
 studies of patients treated with radiation alone.  MRI scanning showed visual
 enhancement of the brain metastases for 56 days following administration of
 motexafin gadolinium, demonstrating how the drug localizes selectively and is
 retained in the tumors.
     The treatment was well tolerated.  The most common side effects observed
 were discoloration of the skin, urine and eyes due to the dark green color of
 the drug.  The discoloration developed gradually after repeated drug dosing,
 and cleared three to four days after the last dose.
     "This is the first treatment of its kind that appears to enhance the
 beneficial effects of radiation therapy in a clinical setting," said Dr.
 Patrice Carde, Chef de Service, Department of Medicine, Institut Gustave
 Roussy, Villejuif, France, lead author of the study.
 
     Brain Metastases: An Increasing Clinical Problem
     Approximately 170,000 patients are diagnosed with brain metastases each
 year in the United States.  This number is increasing as cancer patients live
 longer due to new treatment advances made in the last several years.  However,
 there are few treatment options for patients whose cancer has advanced and
 spread to the brain.
     Metastases in the brain are one of the most devastating consequences of
 cancer, affecting up to 40 percent of all cancer patients. The majority of
 brain metastases originate in breast and lung cancers.  Brain metastases occur
 when cancer cells from the primary site migrate (often through the blood
 stream) and travel to the brain, where they remain and grow.  Patients with
 brain metastases may suffer devastating complications from uncontrolled
 progression of tumor growth in the brain; these complications include
 headaches, seizures, paralysis, blindness, neurocognitive deterioration and
 death.  The goal of whole brain radiation therapy is to reverse or prevent
 neurological deterioration and prevent death due to tumor progression in the
 brain.
 
     About University of Wisconsin Comprehensive Cancer Center
     One of 37 multidisciplinary comprehensive centers funded by the National
 Cancer Institute, the UW-Madison Comprehensive Cancer Center offers standard
 and innovative cancer treatment to patients. The center's research focuses on
 common cancers such as breast, lung and prostate and also emphasizes disease
 prevention. The research is heavily dependent on federal grants and gifts from
 individual donors.
 
 

SOURCE University of Wisconsin Comprehensive Cancer Center
    MADISON, Wis., April 2 /PRNewswire/ -- A promising new approach to
 treating the more than 170,000 cancer patients in the U.S. whose cancer
 spreads from another part of their body to their brain each year may increase
 tumor response rates and reduce progression of the disease, according to a
 study published in this week's Journal of Clinical Oncology.
     The multi-center Phase Ib/II clinical trial of the investigational agent,
 motexafin gadolinium (Xcytrin(R) Injection,
 Pharmacyclics, Inc.; (Nasdaq: PCYC), Sunnyvale, Calif.), administered in
 combination with standard whole brain radiation therapy, showed the treatment
 increased local tumor control, as evidenced by a high tumor response rate
 (i.e., significant tumor shrinkage) and low rate of death due to tumor
 progression in the brain.
     "We are particularly pleased to see the high tumor response rate, which is
 nearly double what we have observed in the literature with radiation alone,"
 said Minesh Mehta, M.D., associate professor and interim chair, Department of
 Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison,
 one of the study's lead investigators.  "Based on these encouraging results,
 we conducted a large multi-center international Phase III study designed to
 measure survival and time to neurologic progression in a similar patient
 population.  Enrollment in this 428-patient trial has been completed, and we
 expect to report results by the end of this year."
     Motexafin gadolinium is the first of a new class of drugs called
 texaphyrins.  It selectively accumulates in cancer cells and disrupts cellular
 metabolism by a unique mechanism of action.  By interfering with the flow of
 energy in cancer cells, motexafin gadolinium makes the tumor more responsive
 to the effects of radiation and chemotherapy without increasing damage to
 normal tissue.
 
     Key Study Findings
     Sixty-one patients with brain metastases were enrolled in the combined
 Phase Ib/II trial.   For 10 days, daily intravenous injections of motexafin
 gadolinium were administered, followed by whole brain radiation treatment each
 day.  Thirty-nine patients were enrolled in the Phase Ib portion of the trial
 intended to determine optimal dosing and tumor localization using magnetic
 resonance imaging (MRI), and 22 patients were enrolled in the Phase II portion
 of the trial designed to assess tumor response and side effect profile.
     Eighteen Phase II patients were evaluable for tumor response based on
 follow-up MRI scans.  After a two-month follow-up, tumor response, defined as
 greater than 50 percent reduction in tumor volume, was seen in 13 of
 18 patients (72 percent), significantly higher than the 43 percent reported in
 previous studies of patients treated with standard whole brain radiation
 therapy alone.  Death due to tumor progression in the brain was just
 12 percent, compared to a rate of about 50 percent reported in previous
 studies of patients treated with radiation alone.  MRI scanning showed visual
 enhancement of the brain metastases for 56 days following administration of
 motexafin gadolinium, demonstrating how the drug localizes selectively and is
 retained in the tumors.
     The treatment was well tolerated.  The most common side effects observed
 were discoloration of the skin, urine and eyes due to the dark green color of
 the drug.  The discoloration developed gradually after repeated drug dosing,
 and cleared three to four days after the last dose.
     "This is the first treatment of its kind that appears to enhance the
 beneficial effects of radiation therapy in a clinical setting," said Dr.
 Patrice Carde, Chef de Service, Department of Medicine, Institut Gustave
 Roussy, Villejuif, France, lead author of the study.
 
     Brain Metastases: An Increasing Clinical Problem
     Approximately 170,000 patients are diagnosed with brain metastases each
 year in the United States.  This number is increasing as cancer patients live
 longer due to new treatment advances made in the last several years.  However,
 there are few treatment options for patients whose cancer has advanced and
 spread to the brain.
     Metastases in the brain are one of the most devastating consequences of
 cancer, affecting up to 40 percent of all cancer patients. The majority of
 brain metastases originate in breast and lung cancers.  Brain metastases occur
 when cancer cells from the primary site migrate (often through the blood
 stream) and travel to the brain, where they remain and grow.  Patients with
 brain metastases may suffer devastating complications from uncontrolled
 progression of tumor growth in the brain; these complications include
 headaches, seizures, paralysis, blindness, neurocognitive deterioration and
 death.  The goal of whole brain radiation therapy is to reverse or prevent
 neurological deterioration and prevent death due to tumor progression in the
 brain.
 
     About University of Wisconsin Comprehensive Cancer Center
     One of 37 multidisciplinary comprehensive centers funded by the National
 Cancer Institute, the UW-Madison Comprehensive Cancer Center offers standard
 and innovative cancer treatment to patients. The center's research focuses on
 common cancers such as breast, lung and prostate and also emphasizes disease
 prevention. The research is heavily dependent on federal grants and gifts from
 individual donors.
 
 SOURCE  University of Wisconsin Comprehensive Cancer Center

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