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That is interesting I had never heard of the Gleevec registry before of
patients who have stopped.
Rob
----- Original Message -----
Sent: Tuesday, May 03, 2005 10:40
AM
Subject: [CML] A very interesting
read.......
Quitting Cancer Drugs
posted: 05/03/05
Doctors Test Whether Patients Can Safely Stop Taking Targeted
Therapies After Years Of Use
THE WALL STREET JOURNAL, 05/03/2005
By Amy Dockser Marcus
In a debate that has far-ranging
implications for the most promising
new "smart drugs" in treating cancer,
some doctors are now starting
to ask: Can patients ever stop taking them?
This is a question that rarely came up with standard chemotherapy
treatments, which often were so toxic that they either killed the
cancer or were stopped because of the potential harm to the patients.
The newer "smart drugs," such as Avastin, Gleevec and Tarceva, which
target only cancerous cells and leave normal ones unharmed, have
milder side effects. They often keep a tumor from growing but don't
completely eradicate it, raising the possibility that they may be
taken for years, possibly for the rest of someone's life,
transforming
cancer into a chronic illness.
Many patients who have been on the
drugs for years are starting to
ask their doctors when, if ever, they can
stop. Some complain that
even the so-called mild side effects, such as
fatigue, nausea,
swollen eyes and legs, among other issues, are difficult
to endure on
a chronic basis. The drugs often are expensive. Novartis's
Gleevec,
for leukemia and gastro-intestinal stromal tumors (GIST), and OSI
Pharmaceuticals Inc. and Genentech Inc.'s Tarceva, approved to treat
nonsmall-cell lung cancer, cost around $2,400 and $2,100 a month,
respectively, at wholesale prices. Genentech's Avastin, which is
approved for colo-rectal cancer, runs around $4,400 a month. Even
people with insurance can end up with large monthly co-payments.
Also, there is only scant data on the potential effects on a fetus,
so both women and men taking the drugs are advised not to have
children, a challenging issue for patients in their reproductive
years.
Now, academic centers such as M.D. Anderson Cancer Center
in Houston;
the French Sarcoma Group, an organization of 36 cancer
institutions
in France and Switzerland; and the Australasian Leukaemia
& Lymphoma
Group, a consortium of centers in Australia and New
Zealand, are
launching clinical trials that will do something that once
was
unthinkable. They will enroll patients with chronic myelogenous
leukemia (CML) or GIST whose cancer is either undetectable by blood
tests or hasn't grown for the past two to three years and see what
happens when some of them stop taking Gleevec.
The current trials
involve Gleevec in part because it was one of the
first smart drugs to win
Food and Drug Administration approval, in
2001, and has a group of
patients who have taken it for more than
three years. The questions raised
in the trials go far beyond Gleevec
users and have implications for all
such drugs. Many patients
eventually become "resistant" to cancer drugs --
GIST patients on
Gleevec have a particularly high rate but it's an issue
for other
targeted therapies, too. One notion that researchers are
exploring is
whether taking patients off a drug for a time will extend the
life of
the drug's efficacy and perhaps delay resistance. Doctors who
treat
patients with breast cancer also are looking into whether longer or
shorter durations of drugs such as Herceptin or Femara help prevent
the cancer from coming back.
"Every targeted therapy is facing the
same key issue: How long do we
treat patients? Two years, five years,
indefinitely?" says Brian
Druker, professor of medicine at Oregon Health
& Science University
Cancer Institute in Portland and one of the
developers of Gleevec.
The trials raise ethical concerns because of
data that have emerged
recently involving small numbers of patients from
Oregon Health &
Science University in Portland, the French Sarcoma
Group's
institutions and M.D. Anderson that indicated the vast majority of
those who stopped taking the drug quickly relapsed. All of these
patients restarted the drug and doctors say there is no evidence that
their overall survival odds are any worse than someone who never
stopped taking the drug. But two GIST patients in one study weren't
able to get their cancer back in control after restarting the drug
and
saw their disease worsen; one has died.
Two years ago, Andreas
Hochhaus of the University of Heidelberg in
Manheim started collecting
cases of patients who, for various
reasons, had stopped taking Gleevec.
The Registry on Patients Who
Stop Gleevec After Remission now contains 20
patients in the U.S. and
in Europe. "Almost all" relapsed, Dr. Hochhaus
said. "I do not think
people can stop taking Gleevec at any point."
Diane Young, vice president of clinical development at Novartis
Oncology, says the company's position is that "right now we don't
really feel there is sufficient data to support that the drug can be
stopped safely in patients" who are doing well on it. Dr. Young said
the limited evidence that exists suggests that even patients whose
disease is undetectable using current tests may still have some
residual disease that can grow if the drug is stopped.
The doctors
setting up the current trials are being driven by the
small yet intriguing
reports being published that showed some
patients were able to go off the
drug and not relapse for extended
periods of time. Jean-Yves Blay,
president of the French Sarcoma
Group, presented data at the American
Society of Clinical Oncology
annual meeting last year involving 259
patients with GIST who were
taking Gleevec. In an interim report, Dr. Blay
said 32 patients were
taken off Gleevec to see how they responded, and 24
of them saw their
tumors start to grow again. The median time to relapse
was six
months. Dr. Blay said he and the other doctors recommended that
everyone go back on the drug, but as of February 2005, four patients
refused to do so and still hadn't relapsed after having been off for
12 to 14 months. Eventually, they all started taking Gleevec again,
because of encouragement from their families. The group's doctors are
studying the patients' tumors to see if there is some kind of
mutation
in the proteins targeted by the tumor that can be tied to
the likelihood
of relapse after stopping the drug.
Dr. Blay said one question that
remains is whether the patients would
have fared better if they had
stopped after being on the drug for a
longer period of time. The patients
in the first trial had been in
remission only for a median of two years.
Later this year, he said
the French Sarcoma Group will start a new trial
involving GIST
patients who have been taking Gleevec for three years with
no sign of
cancer progression, to see if some of these patients no longer
need
the drug.
At M.D. Anderson, Jorge Cortes, deputy chairman of
the department of
leukemia, is enrolling patients in a trial where they
receive Gleevec
and interferon, rather than Gleevec alone. If the levels
of leukemia
cells in their blood remain undetectable for two to three
years, they
then will stop taking the drugs. The idea is "if we add other
drugs
to the Gleevec, maybe it will improve their chances of staying in
remission once they stop taking Gleevec," Dr. Cortes said.
In a
paper published in the journal Leukemia Research, a group of
doctors at
Oregon Health & Science wrote about two patients who
stopped taking
Gleevec. One of them asked to discontinue because of
worsening fatigue.
She relapsed two months later. The second patient,
a 36-year-old woman
diagnosed with leukemia in 2000, stopped taking
the drug after 17 months
because she found out she was pregnant. One
year later, after delivering a
normal child, the levels of leukemia
cells in her blood still were
undetectable, according to the paper.
One month later, despite the fact
that she still remained in
remission, she decided to go back on the drug
after speaking with her
doctor.
Dr. Druker says her case and
others show that "there is a potential
for differing outcomes when the
drug is stopped."
This potential is what convinced Jennie Tilley to enroll
in a 25-
person trial expected to start this fall being run by the
Australasian Leukaemia and Lymphoma Group. Ms. Tilley, 63, was
diagnosed in 1995 with leukemia. She was initially treated with
interferon but had terrible mood swings and lost weight. She had a
bone-marrow transplant but her leukemia counts kept rising. In 2001,
she went on Gleevec. Her disease has been undetectable since 2003.
Ms. Tilley, who lives in Port MacDonnell in the southern part of
Australia, said she has suffered side effects from the Gleevec. She
gets constant subcutaneous eye hemorrhages, which she says are very
painful and feel "like a hot needle is going through your eye." Her
hair "pulls out in chunks," she said. But she said she was most
concerned by a recent study done by Novartis showing an increased
frequency of genitourinary tumors in rats treated with Gleevec daily
for 24 months. Ms. Tilley said the report reminded her that "they
don't know the long-term effects of taking this drug because it is so
new."
Novartis's Dr. Young says the rat study is continuing, but
that in
safety data from more than 9,000 patients, there hasn't been
findings
of increased incidence of any kind of tumor. She added that the
company did send out a letter to physicians in November 2004 about
the
rat data and updated the Gleevec label to reflect the findings.
Ms.
Tilley said the knowledge she can go back on the drug if her
counts go up,
and that others who have done this have been able to
get the cancer back
into control, made her feel that, "I've got a
parachute."
Reasons
To Stop
Why some cancer patients quit taking so-called smart
drugs:
-- Side effects -- The drugs can cause fatigue, swollen eyes
and
legs, nausea and vomiting.
-- Fertility issues -- Both women
and men often are advised to
refrain from having children while taking
these drugs.
-- Cost -- Even patients with insurance can have
significant co-
payments, which add up.
-- Drug resistance --
Some tumors develop mutations that become
resistant to the drug and
require new therapy.
Stopping Cancer Drugs
Clinical trials
starting this year where some patients will stop
taking their medication
to test whether the cancer will progress:
SPONSOR: M.D.Anderson,
Houston TRIAL: Leukemia patients will take
Gleevec and interferon. If they
remain without detectable levels of
cancer in their blood for two to three
years, the drugs will be
stopped.
CONTACT: Jorge Cortes,
713-794-5783
SPONSOR: French Sarcoma Group, 36 institutions in France and
Switzerland * TRIAL: GIST patients whose cancer hasn t progressed for
at least three years will be eligible for a trial where some people
will stop taking Gleevec.
CONTACT: Jean-Yves Blay,
[EMAIL PROTECTED]
SPONSOR: Australasian Leukaemia and Lymphoma Group,
Australia **
TRIAL: Leukemia patients with undetectable levels of cancer
in their
blood for at least two years will be eligible for a trial where
some
people will stop taking Gleevec.
CONTACT:
www.petermac.unimelb.edu.au/allg
*Accredited oncology centers in
the U.S. are eligible to participate
**Available only to patients in
Australia
Copyright (c) 2005 Dow Jones Reuters Business Interactive LLC
(Factiva)
Louis Nault
Montreal, Quebec,
Canada
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