"I am truly grateful to The Leukemia & Lymphoma Society
for having confidence in the work of our team and providing us with
this funding," said Dr. Irish. "I am hopeful that this work will
present new opportunities to increase therapeutic options for people
with AML."
About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society(R), headquartered in White Plains,
NY, with 66 chapters in the United States and Canada, is the world's
largest voluntary health organization dedicated to funding blood
cancer research and providing education and patient services. The
Society's mission: Cure leukemia, lymphoma, Hodgkin's disease and
myeloma, and improve the quality of life of patients and their families.
Since its founding in 1949, the Society has invested more than $424
million in research specifically targeting leukemia, lymphoma and
myeloma. Last year alone, the Society made 2.5 million contacts
with patients, caregivers and healthcare professionals.
For more information about blood cancer, visit http://www.LLS.org or call the Society's
Information Resource Center (IRC), a call center staffed by master's
level social workers, nurses and health educators who provide information,
support and resources to patients and their families and caregivers.
IRC information specialists are available at (800) 955-4572, Monday
through Friday, 9 a.m. to 6 p.m. ET.
The Leukemia & Lymphoma Society
http://www.LLS.org
Nilotinib Appears To Help Chronic Myelogenous Leukemia Patients
When Standard Care Fails
Main Category: Lymphoma / Leukemia News
Article Date: 19 Jun 2006 - 16:00 PST
The targeted agent nilotinib (AMN107) appears to offer striking
benefits in patients with chronic myelogenous leukemia (CML) who
are resistant to Gleevec, the standard therapy for this cancer,
say researchers at The University of Texas M. D. Anderson Cancer
Center.
Results of a 119-patient, phase I dose-escalation study, published
June 15 in The New England Journal of Medicine, show that nilotinib
offers a relatively favorable safety profile and obvious activity,
researchers say, even though the study was not designed to measure
the agent's effectiveness.
"We are very excited about this drug," says the study's
lead investigator, Hagop Kantarjian, M.D., professor and chair of
the Department of Leukemia. "With it, I believe we are going
to make another quantum leap in the treatment of CML, allowing us
to treat our patients according to their cancer's distinct molecular
signature."
Nilotinib is the younger sibling of Gleevec, both of which were
developed by Novartis Pharmaceuticals Corporation, which also funded
the study. Preclinical studies have shown that nilotinib, which
is administered in pill form, is up to 50 times more potent than
Gleevec because it was designed to more efficiently bind to, and
shut down, the protein enzyme responsible for the disease.
v The June 15 NEJM also includes a report on a phase 1 clinical
trial for dasatinib, a medication developed by Bristol-Myers Squibb
for CML and acute lymphoblastic leukemia, and an editorial noting
the importance of both papers' findings for CML patients and for
swift, targeted drug development based on an understanding of cancer
at the molecular level.
While Kantarjian notes that nilotinib seems to have fewer side
effects than Gleevec, which is considered a safe drug, some patients
in this trial were found to have abnormal electrical activity in
their hearts, and one patient experienced two cardiac events. "We
believe this issue is manageable with the right dose of nilotinib
and with careful monitoring, but of course we want to test the agent
further to make sure it is 100 percent safe," he says.
"At this point, Gleevec should remain the standard of care,"
Kantarjian says. "For CML patients who respond to Gleevec,
and most of them do, 93 percent are doing well five years after
treatment."
The study, which included researchers and patients from M. D. Anderson,
the University of Frankfurt and Heidelberg University in Germany,
and the H. Lee Moffitt Cancer Center, tested nilotinib in Gleevec-resistant
patients who had little or no other treatment options available
to them.
The participants had either CML or "Philadelphia-positive"
acute lymphocytic leukemia (ALL). These diseases are caused by the
swapping of genetic material in bone marrow stem cells, which results
in an abnormality called the Philadelphia chromosome, and creation
of a new gene. This gene produces the fusion protein, BCR-ABL, which
leads to development of leukemia. Gleevec and nilotinib both bind
to, and inactivate, BCR-ABL.
In the trial, researchers continually increased the dose of nilotinib
from a low of 50 mg. to as much as 1,200 mg. daily in some patients.
Nilotinib improved outcomes in all three forms of CML, and was
most effective in treating chronic phase CML, Kantarjian says. Of
the 12 patients in this category, 11 had a complete hematological
remission of their cancer, meaning a disappearance of all findings
consistent with advanced stage CML, and return of blood counts to
normal.
A total of 13 of 33 patients in the blastic phase of the disease
disease - the most advanced stage - had a hematological response
(defined as control of white blood cell counts), and 9 had a cytogenetic
response (elimination of cells with the cancer-causing defect).
Of 46 patients in the accelerated phase, 33 had a hematological
response and 22 had a cytogenetic response.
The agent had less activity than expected in patients with ALL.
Only 2 of 13 patients responded, and that may be because the cancer
was too advanced to be affected by a single drug, Kantarjian said.
The researchers also found that nilotinib's side effects were quite
tolerable, and different than those seen with Gleevec. They included
myelosuppression (a reduction in the ability of the bone marrow
to produce blood cells), transient increases in bilirubin due to
breakdown of red blood cells, and skin rashes.
Kantarjian adds that occasional patients experienced an abnormally
long "QTcF" interval, a measurement of the time between
the onset and the end of electrical activity in the heart's ventricular
chamber. Prolongation of this interval is considered a marker of
a cardiac arrhythmia. One patient had two adverse cardiac events
that were associated with use of nilotinib, and one sudden death
was reported in a patient beyond the follow-up time analysis, he
says, but the cause of that death is unknown.
"This finding indicates the need for careful monitoring for
cardiac events and arrhythmias in all patients who are receiving
nilotinib, and a strict avoidance of medications that may prolong
the QTcF interval," the researchers write in their paper.
"We would like to see, in the long run, if there are any unusual
side effects to nilotinib, and then directly compare it with Gleevec
in newly diagnosed CML patients," Kantarjian says. "In
the future, nilotinib could possibly emerge as the standard of care."
Co-authors of the study include, from M. D. Anderson: Francis Giles,
M.D., Susan O'Brien, M.D., and Jorge Cortes, M.D.; from J. W. Goethe
Universitat, Frankfurt: Oliver G. Ottmann, M.D., Lydia Wunderle,
M.D., Barbara Wassmann, M.D., and Dieter Hoelzer, M.D.; from Novartis
Pharmaceuticals: Chiaki Tanaka, M.D., Paul Manley, M.D., Patricia
Rae, William Mietlowski, Ph.D., Kathy Bochinski, Margaret Dugan,
M.D., and Leila Alland, M.D.; Andreas Hochhaus, M.D., from the Univeristate
Heidelberg; Kapil Bhalla, M.D., from Moffitt Cancer Center; Maher
Albitar, M.D., Ph.D., from Quest Diagnostics; and James D. Griffin,
from the Dana Farber Cancer Center.
###
From M. D. Anderson, Kantarjian reports having received lecture
fees from Bristol-Myers Squibb and Novartis Pharmaceuticals and
research grants from Bristol-Myers Squibb, Novartis Pharmaceuticals
and MGI Pharma. Giles and Cortes reports having received research
grants from Bristol-Myers Squibb and Novartis Pharmaceuticals. These
arrangements are managed by M. D. Anderson in accordance with its
conflict of interest policies.
Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center
New Research On The Mechanisms That Control Blood Cells Of Acute
Myelogenous Leukemia Patients May Lead To Better Targeted Therapies
Main Category: Lymphoma / Leukemia News
Article Date: 10 Jun 2006 - 0:00 PST
New findings to be published in the journal Blood strongly suggest
that new drugs under development for acute myelogenous leukemia
(AML) patients would be much more effective if used in specific
combinations most appropriate to the individual patient, leading
to better and more specifically targeted therapies for these patients
with fewer side-effects.
Patients with blood cancer frequently have hyperactive "signal
transduction pathways" -- the mechanisms by which the blood
cells receive control signals from other cells. These defects in
control pathways within cancer cells lead to uncontrolled growth,
inappropriate migration and/ or resistance to killing by standard
anti-cancer drugs.
Doctors at M.D. Anderson Cancer Center in Houston have been studying
these cellular defects in AML patients and will report their findings
in Blood. The doctors, led by Steven Kornblau, M.D., used samples
from 188 patients and found that the simultaneous hyperactivity
of three control pathways (PKC-alpha, ERK2 and AKT) is common in
AML patients and is associated with especially poor prognosis for
these patients.
Dr. Kornblau's team reasoned that if multiple pathways are frequently
simultaneously activated in AML patients, then the new treatments
that target single pathways will not be optimally effective if used
alone.
Rather, Kornblau's team suggests that new drugs being developed
to inactive these pathways -- the PKC-alpha, ERK2 and AKT signal
transduction pathways
-- will be most beneficial when used in combinations individualized
for each AML patient.
"Hopefully these findings will lead to the development of
diagnostic tests to identify the unique constellation of signaling
abnormalities in AML patients and the coordinated use anti-leukemia
drugs targeting these pathways on an individualized basis,"
Dr. Kornblau said.
Dr. Kornblau is the recipient of a Translational Research Grant
from The Leukemia & Lymphoma Society, a program that supports
outstanding investigative research showing strong promise of translating
basic biomedical knowledge into new and better treatments for blood
cancers. The program's goal is to accelerate the transfer of findings
from the laboratory to clinical application, ultimately prolonging
and enhancing patients' lives.
"The goal of the Translational Research Program is to provide
researchers with the resources to advance diagnosis, prevention,
or treatment of blood cancers in the near term," said Marshall
Lichtman, the Society's Executive Vice President for Research and
Medical Programs. "Dr. Kornblau's research may lead to more
effective treatments for AML patients with fewer side effects."
Dr. Kornblau said that the Society's support was fundamental in
moving his research forward.
"I am truly grateful to The Leukemia & Lymphoma Society
for having confidence in my work and providing me with this funding,"
Dr. Kornblau said. "I am hopeful that our work will improve
the outcomes for AML patients."
About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society(R), headquartered in White
Plains, NY, with 66 chapters in the United States and Canada, is
the world's largest voluntary health organization dedicated to funding
blood cancer research and providing education and patient services.
The Society's mission: Cure leukemia, lymphoma, Hodgkin's disease
and myeloma, and improve the quality of life of patients and their
families. Since its founding in 1949, the Society has invested more
than $424 million in research specifically targeting leukemia, lymphoma
and myeloma. Last year alone, the Society made 2.5 million contacts
with patients, caregivers and healthcare professionals.
For more information about blood cancer, call the Society's Information
Resource Center (IRC), a call center staffed by master's level social
workers, nurses and health educators who provide information, support
and resources to patients and their families and caregivers
The Leukemia & Lymphoma Society
http://www.LLS.org
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