CML

FDA: Proposed Bristol-Myers Drug Appears To Slow Leukemia
June 1, 2006: 10:55 a.m. EST
By Jennifer Corbett Dooren Of DOW JONES NEWSWIRES ATLANTA -(Dow Jones)-
The U.S. Food and Drug Administration said Thursday a proposed drug
from Bristol-Myers Squibb Co. (BMY) appears to slow the progression of
certain types of leukemia in patients who failed other treatments
including Novartis AG's (NVS) Gleevec, based on preliminary clinical
studies.
The FDA posted its review of the drug, dasatinib, on its Web site
Thursday, a day before an outside panel of medical experts is set to
make recommendations about whether the agency should approve the drug.
The FDA's oncology advisory panel meeting will be held in Atlanta to
coincide with the American Society of Clinical Oncology's annual
meeting, which brings together top cancer researchers and experts.
Specifically, Bristol-Myers is seeking FDA approval for dasatinib to
treat patients with chronic myeloid leukemia, or CML, who have failed
treatment with other therapies such as Gleevec and the treatment of
adults with Philadelphia chromosome-positive acute lymphoblastic
leukemia and lymphoid blast chronic myeloid leukemia who have failed
other treatments.
Bristol-Myers submitted four Phase II studies looking at 551 patients
with different types of leukemia. All of the studies show dasatinib,
which the company has proposed selling under the brand name Sprycel,
either halted the progression of the disease or made it undetectable
in several patients. The drug showed a response rate in a range of 31%
to 74% of patients depending on which type of leukemia they had.
However, the patients haven't been followed long enough to determine
whether treatment with dasatinib improves overall survival.
The studies also showed that almost all patients suffered from an
adverse event, such as diarrhea, nausea and vomiting, that likely was
caused by the drug. About 66% of patients suffered more serious
problems including fluid retention, a worsening of underlying blood
problems such as anemia and, in some cases, cardiac problems.
One of the issues the panel will consider is whether a lower starting
dose of dasatinib should be recommended in order to lower the rate of
adverse events. The panel also will be asked whether the company has
submitted enough data "to recommend dasatinib for the imatinib
(Gleevec) intolerant population," the FDA said in a memo.
When considering cancer drugs, the FDA sometimes accepts earlier Phase
II studies rather than larger Phase III studies it typically requires
most companies to submit with drug-approval applications. The FDA can
grant so-called accelerated approval of a drug based on Phase II
studies. But to gain full approval, companies must eventually submit
Phase III data. In 2001, the FDA approved Gleevec for the treatment of
chronic myeloid leukemia based on preliminary Phase II data. Novartis
later gained full approval for Gleevec for CML and then received
approval to treat a rare type of gastrointestinal cancer.
Some patients have developed resistance to Gleevec and there's
currently no FDA-approved treatment for CML patients who are
Gleevec-resistant. So far, the studies of dasatinib suggest the drug
works in many of those patients.
Bristol-Myers said it is "likely treatment with dasatinib will result
in a survival benefit in patients," based on the the Phase II data
which showed the drug produced a so-called cytogenetic response in
many patients.
The FDA typically follows its panel's advice, but isn't required to.
The agency is expected to make a final decision on dasatinib by the
end of the month.
The agency granted dasatinib priority review status, which the agency
grants to drugs or products that it believes are an advance over
existing treatments. It cuts about four months off of the typical
10-month FDA drug-review period.
In recent trading, Bristol-Myers shares were up 29 cents, or 1.2%, at
$24.84 on volume of 1.5 million. Average daily volume is 7.3 million.
-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294;
Jennifer.Corbett@...

ASCO drug conference opens Friday
Annual meeting on cancer treatments a premier medical event
By Val Brickates Kennedy, MarketWatch
Last Update: 4:16 PM ET Jun 1, 2006
BOSTON (MarketWatch) -- Cancer drug makers are gearing up for one of
the biggest market moving events of the year, the annual meeting of
the American Society of Clinical Oncology, or ASCO, where over 25,000
medical professionals will gather to get updated on the latest and
greatest oncology treatments.
Considered one of the premier medical events, ASCO provides a unique
opportunity for drug developers to roll out their latest clinical
results before the very people who drive their sales -- cancer
specialists. The meeting opens in Atlanta on Friday, June 2, and will
run through Tuesday, June 6.
Unlike past years, when ASCO news was dominated by such biotechnology
heavyweights as Genentech, old-line pharmaceutical firms are expected
to grab headlines this year, with Bristol-Myers Squibb's Sprycel and
GlaxoSmithKline's Tykerb potentially creating the most buzz.
"All-in, we believe this year's ASCO is shaping up to highlight large
pharma's competitive threat to biotech in addition to the ever-present
biotech/biotech competition," said Robert W. Baird analyst Christopher
Raymond, in his brief note on the event.
Here's a round up of presentations Wall Street analysts will be
watching closely, especially from Big Pharma:
Bristol-Myers Squibb
In a highly unusual move, the FDA has decided to convene an advisory
panel at ASCO this year to review Bristol-Myers market application for
Sprycel, its much-anticipated therapy for CML, or chronic myelogenous
leukemia. While the agency is not bound to the recommendations of its
panel of experts, it generally follows them.
The FDA meeting is slated for June 2, with the agency expected to make
a final decision on the drug by June 28.
In general, analysts believe that the committee should give Sprycel
the thumbs up.
"Our physician experts believe a recommendation for Sprycel is highly
likely based on reasonable tolerability and excellent efficacy," wrote
analysts at Cowen & Co. of the FDA meeting.
Also a potential market mover will be Bristol-Myers' June 3
presentation of additional Phase III data on Sprycel, also known as
dasatinib, for CML. The drug is initially being targeted for patients
with CML who don't respond well to Novartis AG's Gleevec, the current
standard treatment for the disease. In particular, the market will be
looking for data on how well Sprycel performs against high doses of
Gleevec.
On June 4, Bristol-Myers will be presenting Phase II data for another
one of its oncology products, MDX-010, for advanced melanoma.
According to Bank of America, Bristol-Myers is still trying to figure
out whether to pursue applying for approval of the drug in combination
with other cancer drugs or as a monotherapy. "We will also be closely
watching any side effect data from trials, particularly
immune-mediated events," wrote the analysts.

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Most CML patients on Gleevec alive after 5 years
Sat Jun 3, 2006 3:03 PM ET
ATLANTA, June 3 (Reuters) - Nearly 90 percent of patients with chronic
myelogenous leukemia who were treated with Novartis AG's <NOVN.VX
were alive after five years, new data shows, compared to the no more than 50
percent survival rate with other therapies.
Data presented on Saturday at the annual meeting of the American Society of
Clinical Oncology in Atlanta showed that at five years, the overall survival
of 553 patients who received Gleevec as their initial therapy was 89
percent.
"This trend, if it holds, coupled with the low risk of relapse, means that
the possibility of long-term survival with CML is increasingly likely," said
Dr. Brian Druker, who helped develop Gleevec and is a chair of leukemia
research in the Oregon Health & Science University Cancer Institute.
The typical rate of survival of patients who took other therapies was no
more than 50 percent, investigators said.
The trial was begun in 2000 and involved 1,106 subjects. Half received
Gleevec and half received standard treatment at the time the trial started
-- interferon-alpha and cytarabine arabinoside. Participants were allowed to
cross over to the Gleevec group and only 3 percent remain on interferon.
Gleevec was approved in 2001 by the U.S. Food and Drug Administration. In
2002 it was approved for gastrointestinal stromal tumors (GIST), a rare form
of abdominal cancer, in 2002.
About 4,600 new CML cases are diagnosed each year in the United States,
according to The Leukemia & Lymphoma Society.
On Friday, an FDA advisory panel recommended the agency approve an
experimental Bristol-Myers Squibb Co. <BMY.N
failed other treatments.
The drug, Sprycel, reduced or eliminated leukemia cells in some patients who
had stopped responding to Gleevec or could not tolerate it.
So far it is unknown how long the effects last or whether patients live
longer, FDA reviewers said.

http://www.signonsandiego.com/news/business/biotech/20060601-1054-health
-cancer-conference.html
Big Pharma expected to dominate key cancer meeting
By Deena Beasley
REUTERS
10:54 a.m. June 1, 2006
LOS ANGELES - Biotechnology may have blazed the trail, but big pharma is
fast advancing in the competition to develop innovative cancer
treatments.
Companies like Genentech Inc., long seen at the cutting edge of cancer
research, are expected to take a backseat to the mainline pharmaceutical
industry at an annual meeting of oncologists starting this weekend.
"Biotech had the field to itself for a while, but now there are players
of all sizes," said Geoffrey Porges, an analyst at Sanford Bernstein.
Last year, Genentech's Avastin - the first cancer drug designed to work
by cutting off blood supply to tumors - dominated the meeting of the
American Society for Clinical Oncology (ASCO).
This year, big pharmaceutical companies like Wyeth, Pfizer Inc., and
GlaxoSmithKline Plc, will be announcing pivotal-stage trial data for
their own targeted cancer drugs, which are gentler on patients than
chemotherapy, which can cause severe nausea and other harsh side
effects.
Facing looming generic competition for some of their most profitable
products, drugmakers like Pfizer and Bristol-Myers Squibb have been
penalized by investors for not doing enough to develop new medicines.
As a result, many licensed, acquired or developed novel drugs for
diseases like cancer, the No. 2 killer in the United States after heart
disease.
"Big pharma realizes that this is an important area. Some are investing
more than they have before," said Dr. David Schenkein, Genentech's vice
president of clinical oncology and hematology.
He noted that Genentech will have 200 abstracts at the meeting this
year, "clearly a strong leadership position."
Most of that research will be "incremental" or involve combinations of
therapies, he said.
Schenkein attributed the shift to an increase in cancer cases as the
population ages and people live longer as well as advances in biology
that are opening new treatment pathways.
"All in, we believe this year's ASCO is shaping up to highlight large
pharma's competitive threat to biotech in addition to the ever-present
biotech/biotech competition," Robert Baird & Co. analyst Christopher
Raymond said in a report.
Other biotech companies, including Amgen Inc., the world's largest, are
expected to unveil important cancer research at the meeting, but most of
the late-stage presentations will come from traditional pharmaceutical
companies.
Glaxo is expected to present data on its experimental pill Tykerb in
breast and kidney cancer, while Pfizer will unveil trial results for
Sutent in kidney and stomach cancer. Wyeth is slated to report results
for kidney cancer drug temsirolimus and Novartis AG will present interim
colon cancer results for its drug known as PTK787.
Also at the ASCO meeting in Atlanta, a U.S. Food and Drug Administration
advisory panel will review Bristol-Myers Squibb's application for
experimental leukemia drug Sprycel.
Big pharma's interest in cancer comes about five years after Novartis'
launch of the targeted leukemia drug Gleevec.
Gleevec was initially expected to be a niche product, but its
effectiveness and benign side-effect profile led to sales last year of
$2.2 billion.
Cancer drugs are now the fastest-growing section of the pharmaceutical
market and are perceived to be relatively immune from the cost pressures
that increasingly weigh on the U.S. health-care system.
"Oncology has become a long-term market as more people are living with
the disease," said Mark Monane, an analyst at Needham & Co.
"In old movies they used to call it 'the big C.' The name cancer was
unmentionable. Now, with all the new therapies, I don't think we are
curing people, but we are caring for them," Monane said.

By Althea Chang
TheStreet.com Staff Reporter
6/2/2006 5:15 PM EDT
Click here for more stories by Althea Chang
The Bristol-Myers Squibb (BMY:NYSE - commentary - research - Cramer's
Take) cancer drug Sprycel got the nod from an advisory panel to the
Food and Drug Administration for the treatment of certain types of
rare blood cancers.
According to a drug advisory committee's review of clinical trial
data, Sprycel is effective for certain types of chronic myeloid
leukemia, as well as a type of acute lymphoblastic leukemia in
patients who couldn't tolerate or didn't respond to prior drug
therapies, including Novartis' (NVS:NYSE ADR - commentary - research -
Cramer's Take) Gleevec, a standard treatment for the diseases.
Because of the strength of the trial results, the committee believes
Sprycel should be granted accelerated approval for use against chronic
myeloid leukemia. The committee's decision on Friday to recommend that
the full FDA clear the drug was based on an early phase I study
conducted to determine the safest dosages of the drug and five phase
II studies on the safety and effectiveness of Sprycel. A total of 551
patients were enrolled and treated.
While the FDA doesn't have to agree with the advisory committee's
recommendation, it usually follows the suggestions of its panels.
Documents posted by the FDA on its Web site did say that 99% of
patients who took Sprycel had at least one negative side effect,
including fluid retention, anemia, bleeding, gastrointestinal side
effects or heart attacks. In addition, six central nervous system
hemorrhages occurred, five of which were fatal.
Chronic myeloid leukemia is diagnosed in about 4,300 people each year
in the U.S. and accounts for 14% of adult leukemia cases, according to
the FDA. There is currently no approved treatment for the
Gleevec-resistant version of the disease.
Sprycel, also known by the name dasatinib, has already been granted
priority review status by the FDA, a designation given to drugs that
could be a significant improvement from existing therapies. The FDA is
expected to make its decision by June 28.
Bristol-Myers Squibb's shares rose 12 cents, or 0.5%, to $25.27.

Hi:
I would like to address this to all of you who are in a position to make a
donation to the Leukemia Society in the name of Dr. Charles A. Koller, who
is planning once again to participate in this year's bicycle relay with the
Houston Police Department. Fred and I have just made a contribution to Dr.
Koller's relay, as well as to Dr. Mauro's fundraiser for the Leukemia
Society. We were happy to do so, as these contributions will help us all in
promoting research to achieve an eventual cure for leukemia.
I wanted you all to know that Dr. Charles A. Koller, my M. D. Anderson
Cancer Center doctor, is once again planning on participating in this year's
25th Annual Bicycle Relay with the Houston Police Department Bicycle Relay
Team. Dr. Koller has participated in several of the bicycle relay trips in
the past, though unfortunately had to sit out one year when he suffered the
removal of a cancerous kidney. He is now happy to be back to normal with
his health and is therefore once again donating his time and efforts to the
cause of eliminating the scourge of leukemia. This year's relay will be for
3000 miles, from Houston, Texas, to the final destination of Victoria,
British Columbia, Canada. The relay team will be leaving Houston, Texas, on
Tuesday, June 20, 2006, and will arrive in Victoria, British Columbia, on
July 1, 2006.
Dr. Koller states: "I am proud to say, my patient, John Morton, a survivor
of Acute Promyelocytic Leukemia, will be joining the team. John's form of
AML, had a median survival of only 4 weeks five years ago, and now most of
the patients are cured. He is a living example of the benefit of clinical
research in the quest for the cure of leukemia!"
Participants in this efforts use their own vacation time for the
fund-raising event. Dr. Koller's blog from last year's relay which raised
$235,000 for the Leukemia & Lymphoma Society can still be seen at http://www
mdanderson.org/featured_sites/hpdrelay.
So we would like to invite all of you who are able to contribute, to send a
check for whatever amount you wish to donate, made out to "The Leukemia and
Lymphoma Society" and mail it to Dr. Charles A. Koller, MD, MD Anderson
Cancer Center--Box 428, 1515 Holcombe Blvd., Houston, TX 77030-4009.
Thank you all so much for your generosity.
Margot

Hello All,
Please read the news release below. I watched the live webcast of
this today and it was quite interesting. More news later.
Cheers and Congratulations to BMS!
PRINCETON, N.J. (AP) - Drug maker Bristol-Myers Squibb Co. said
Friday that a Food and Drug Administration advisory panel
recommended accelerated approval of the company's dasatinib compound
to treat two kinds of cancer.
The panel recommended the agency approve the drug, based on results
of clinical trials, to treat adults in all phases of chronic myeloid
leukemia when other treatments including Novartis AG's Gleevec
cannot be tolerated or do not work.
The advisory panel also recommended the drug be approved to treat
adults with Philadelphia chromosome-positive acute lymphoblastic
leukemia who are resistant to Gleevec.
Both cancers, which usually occur in adults, are diseases where too
many white blood cells are made in the bone marrow.
While the FDA is not bound by the recommendations, the agency
usually follows the panel's advice. A decision is expected by June
28.

Hi Jennifer,
I also received a note from Dr. Mauro. Thank you for posting.
He was my trial doctor back in 2001. I am one of those fortunate
patients who was treated by him and got to know him and the OHSU staff
as friends.
My plan is to contact all the CML Zero Club members and ask them to
contribute to make Katie's words come true.
Zavie
$102 in the Zero Club

Sprycel Dose Reduction To Be Considered By ODAC During ASCO Road Show
FDA will ask its Oncologic Drugs Advisory Committee whether a lower
initial dose of Bristol-Myers Squibb's Sprycel (dasatinib) for
chronic phase chronic myeloid leukemia patients is appropriate during
a June 2 meeting.
In a briefing document for the panel, FDA suggested that a 50 mg BID
dose, rather than the 70 mg dose studied in the primary efficacy
trials may reduce toxicity without sacrificing efficacy.
Bristol is seeking indications for the multi-kinase inhibitor in
Gleevec-resistant (Novartis' imatinib) chronic, accelerated or blast
phase CML patients and Philadelphia chromosome positive acute
lymphoblastic lymphoma and lymphoid blast CML patients. Sprycel's
priority review user fee date is June 28.
The meeting will be held at the Omni Hotel in Atlanta in conjunction
with the American Society of Clinical Oncology annual meeting.
Bristol conducted a Phase I dose escalation study of dasatinib in
patients with a variety of hematologic malignancies.
"The Phase I study did not determine a maximum tolerated dose;
therefore the applicant chose the recommended dose for Phase II based
on efficacy observed," the briefing document states. "However, in the
Phase I study, efficacy was observed at doses lower than the
recommended Phase II dose."
FDA notes that in chronic phase CML patients "there was no evidence
of a linear dose response," with the majority of the major cytogenic
responses (MCyR) occurring in patients in the 50 mg BID, or 105
mg/day and 70 mg/BID cohorts. Higher and lower cohorts had fewer
responses, the agency adds.
"Based on evidence of [complete hematologic response] and MCyR at
doses lower than 70 mg, a starting dose of 50 mg BID or lower may be
appropriate in chronic phase disease, with dose escalation as needed
based on response and toxicity," the agency concludes.
Major toxicities associated with dasatinib seen in clinical trials
include bleeding events, myelosuppression, fluid retention,
gastrointestinal events, congestive heart failure/left ventricular
dysfunction and QT prolongation.
In addition to the potential to reduce toxicity via a lower starting
dose, the other issue FDA identified with the application is "whether
sufficient data have been provided to recommend dasatinib for the
imatinib tolerant population."
Bristol's application includes data from the Phase I trial and four
Phase II trials in a total of 445 Gleevec-resistant or intolerant
patients with hematologic malignancies.
The MCyR rate after 12 weeks in studies in chronic phase CML patients
was 45%. In the remaining studies major hematologic response rates
after 12 weeks ranged from 30% to 60%.
Bristol will also present data at the advisory committee meeting and
ASCO from a randomized trial (CA 180017) comparing standard-dosed
dasatanib with high dose imatinib in imatinib-resistant patients.
According to FDA's briefing document, "preliminary efficacy results
include a MCyR of 45% in the dasatinib arm and 21% in the imatinib
arm."

Hi all,
I had a note from Dr. Mauro (one of my previous docs during my STI571
clinical trial days) and he also included the announcement below about
his campaign for the LLS's Man of the Year. I think that any of you who
know Dr. Mauro or any of the team at OHSU can appreciate the
tremendously valuable contributions they have all made to advancing CML
treatment, not to mention their compassion and support for patients.
Please take a few moments to read his note -- and then put your vote
where your wallet is and make a donation to Dr. Mauro's campaign. The
money doesn't go to him -- it goes to the LLS, which turns around and
funnels that money into patient services and research. I don't think
there's anyone among us who has not benefitted from this work.
Also, please forward this to your family and friends so that they can
also help make a difference! These good folks give and give and give to
us -- now let's give back!
(I'm doing my part -- I've raised over $6,000 so far for the LLS this
year and will participate in the Anchorage half-marathon, health
willing, on June 17.)
Jennifer G.
www.cmlsupport.com
==============================================
Note from Dr. Michael Mauro:
First of all, thank you for your willingness to put up with me by
reading this fundraising appeal (not to mention your willingness to
withstand bone marrow studies, blood draws, my occasional (? frequent)
tardiness in the clinic, and your bravery and courage in fighting CML or
any other blood cancer). You know me as Michael Mauro, your leukemia
physician at Oregon Health & Science University. You likely know I came
to Oregon 6 years ago to work on a special project at OHSU to develop a
drug then called STI571, now Gleevec. Having just celebrated 5 years of
FDA approval, Gleevec has changed the face of cancer therapy,
revolutionizing the treatment of CML by offering an alternative to bone
marrow transplant and remarkable remissions to most patients. As well,
the example of Gleevec has energized the search for similar "targeted"
therapies for all cancers and hopefully is just the start of things to
come in CML and other conditions.
You may not know that I am also Vice President on the board of the
Portland chapter of the Leukemia and Lymphoma Society (LLS), one of the
biggest charitable organizations supporting research, education, and
patient services for blood-related cancers. The original research and
patient trials testing Gleevec were supported and made possible by grant
support from the Leukemia & Lymphoma Society. I serve on the board of
the LLS as I see no better way to give back to the organization that
believed in our work and the vision of my mentor, Brian Druker, and my
efforts now help raise funds for further research, patient education and
family services for all those battling blood related cancers.
Each year, the LLS holds a fundraising event called "Man and Woman of
the Year"; this year I was nominated to be one of the candidates.
Despite its name, it is fortunately not self-promotion but rather about
fundraising for the cause and honoring a local boy and girl of the year
battling blood-related cancer. When asked to run, I could not say no
given how strongly I feel about the importance of the work we do. My
goal is to make true the words uttered by Katie, a 10 year old girl with
CML whom I know well, when she heard about my campaign: "Dr. Mauro isn't
running for Man of the Year; He is going to WIN Man of the Year!"
There are a few different ways to help:
1/ If you are in the Portland area on June 5th, I am hosting a
fundraising dinner at Hurley's Restaurant (1987 NW Kearney). The theme
of the evening will be "Three Generations of Success" with special
guests who will share their CML stories, and other surprises in the
works; a wonderful evening is guaranteed. This is my favorite restaurant
in Portland; the chef is a retired NYC fireman who creates the most
wonderful French dishes. Wine will be provided by Owen Roe Wines.
Tickets will be $150 per person. Please let me know directly if you are
interested in attending so I may hold tickets for you (email me at
maurom@... or phone me at 503-494-0376).
2/ If you are in the Portland area on June 14th, the grand finale event
for the Portland Man and Woman of the Year will be held at the
headquarters of Wieden+Kennedy (224 NW 13th Avenue); a reception with
food and wine, silent and live auctions, and announcement of the winners
will take place that night. Tickets are $25, and hopefully if you come
my auction items might beckon you to bid*.Let me know as well if you are
interested in this as I will hold tickets (email me at maurom@...
or phone me at 503-494-0376).
3/ The society has provided me with a webpage for direct donations to my
campaign. Dollars equal votes in this campaign, so every bit counts. The
weblink is:
<http://www.active.com/donate/ormwoy/orMMauro
http://www.active.com/donate/ormwoy/orMMauro
As well, donation (a check can be made out to the Leukemia & Lymphoma
Society) along with the enclosed donor form can be sent to my office at
OHSU to the following address:
Michael J. Mauro MD
Center for Hematologic Malignancies
Oregon Health & Science University
3181 SW Sam Jackson Park Road
Mailcode UHN-73C
Portland OR 97239
It is not like me to ask of others, especially those who have a lot on
their shoulders already. I ask without obligation of you, in part
because I know if I didn't let you know about this, many would be mad
for me not telling; I also ask because I know you feel as strongly as I
do about how important our work, your battle, and our future success is
and that it depends on sustained research like the initial and ongoing
research in CML surrounding Gleevec that would not be possible without
help from the Leukemia and Lymphoma Society. Please feel free to spread
the word to others battling CML, to friends, family, to anyone
interested in the cause.
Again Thank You, and Be Well Always,
Michael
Michael J. Mauro, MD
Assistant Professor, Center for Hematologic Malignancies Oregon Cancer
Institute Oregon Health & Science University Portland OR 97239

Chat Reminder - Tuesday 9:00 PM Eastern
Photo: Tulip on front lawn.

Cheryl-Anne and Suzan,
Dr. Goldman is very accessible and I think would answer your outstanding
questions by email. If you'll write to me privately I'll give it to you although
you probably already have it. Or, if you have questions you'd like to have
covered I'd be happy to follow up at my next appointment with him which is June
30. In addition to blood work, interview with an intern, I always have a good
long time to chat with Dr. Goldman.
Susan L

Dr Goldman's talk - May 24, 2006 - Montreal
As mentioned in my previous message, essentially Dr. Goldman covered a short
history of CML and then talked about current approaches to treatment. When
it came to the question of how Gleevec made it to expanded clinical trials,
he thought it was his patient in the UK who started a petition on line. We
pointed out that it was our very own Suzan McNamara who was present with us.
He was thankful that we corrected him. Afterwards we were thinking that
perhaps he was thinking about the petition in the UK?
He fielded a number of questions:
We brought up our interest in immunotherapy, and knowing that he is
currently working in this area we were quite interested to hear what he
might have to say. He told us that he is just in the very preliminary
stages of getting a clinical trial underway. He was quite cautious to give
us too many details, so we will just have to keep a watch out for more news
in the future. As you can imagine, this area of research is quite
competitive!
Interestingly, he stated, rather convincingly too, that he felt that perhaps
we might find in the future that some patients, albeit a very small
fraction, might be able to stop IM (but only after several years of
continuous PCRU - is there anyone who has achieved several years of
continuous PCRU, without any fluctuations?)and maintain undetectable level
remission similar to INF. He is interested to find out, as others are, why
this may be so. He emphasized however, that patients should not stop IM
because most patients relapse fairly quickly. We will have to keep our eyes
open for any new data about this.
He was asked about pregnancy (we have a few young patients in our group).
He told us that there have been a number of cases of mothers with CML on IM
who have become pregnant and that this data is being tracked quite closely
at Novartis. He pointed out that some of the pregnancies have resulted in
normal healthy births and children. He spoke about one case where the
patient was already 9 weeks pregnant and was on IM. Of course the first
trimester is where IM would pose the most teratogenic risk, so it is more
like a case of shutting the barn door after the horse is already out.
However, after careful consideration and consultation with Novartis (who
advised/suggested a therapeutic abortion) the decision was to stop IM and
allow the pregnancy to continue. Mother and baby are fine and the mother
re-started IM 4 months after the baby was delivered. He also mentioned that
there were reports of spontaneous abortions, and foetal malformations, so
while there have been a number of live healthy births, the recommendation is
to avoid Gleevec and pregnancy, er, I mean avoid getting pregnant while on
Gleevec ;
Pregnancy!!!! <just too funny, I couldn't resist
We asked what is the significance, if any, of having hypocellular marrow for
years while undergoing Gleevec therapy? Do you think that there will be any
long term adverse effects from this? Dr. Goldman that it is something that
is common, but that there doesn't seem to be anything to worry about.
There was a question about at what point can a patient safely reduce the
dose of IM? These would be patients who started on a 600 mg or 800 mg dose
and achieved CCR. These are patients whose QOL is compromised because of
side effects from IM. His response was that the dose should not be reduced
as there is no data that would support doing so.
We asked about our concern with staying on IM (or any other drug for that
matter) for significant durations of time at very low or undetectable levels
of disease. The concern of course being that even at PCRU there are still
quite a few CML cells that could potentially wreak havoc at some time in the
future. He seemed to be less concerned with this, saying that as long as
you have a 3 log or better reduction you should just stay with IM. In
thinking about this, I wish we could have been more clear with him. We
really wanted him to talk about a true cure.
On the subject of hormone issues with Gleevec therapy. e.g. missed menstrual
cycles, heavy periods, breast enlargement, he really didn't have much to add
about this but if I remember correctly, he did say that Novartis was
tracking this.
He basically said that Dasatinib and Nilotinib are essentially the same
drugs with regards to performance, although I do not quite understand how
that could be so. I think it is a bit premature to say that as Dasatinib
has been used on more patients than Nilotinib. However, we just have to
remember that this was his opinion and he reminded us that his opinion might
vary from ours and our treating doctors opinion.
We thanked Novartis for sponsoring Dr. Goldman, in fact someone from
Novartis joined us, which was a bit of a surprise, it did change the tone of
the meeting though. We've had some of our best productive meetings when it
is just us patients with our doctors.
Dr. Goldman is a delightful person and we were very happy to meet him. We
thanked him and gave both he and Dr. Pierre Laneuville each a very nice
bottle of wine with cards signed by all of us. We hope Dr. Goldman will
come back and visit us again as a guest of the CML Society.
I should mention that the CML Society is holding our first board meeting
next week and we will be putting together our agenda of activities for this
coming year. We will be posting the minutes and updating the website so,
stay tuned.
Cheryl-Anne and Suzan

Well I am back on steroids again for another 6 days. At least I will
have a better weekend. Thanks to all of your suggestions you helped me
greatly. I guess what I do know now is that is it going to be a longer
healing than I guessed.
Happy Memorial Day to everyone. Have a safe fun weekend.
Joan P.
dx'd 8/03
#662
Gleevec 400 mg

Chat Reminder - 10:00 AM - Saturday
Photo - Tomatoes at S.O.G.H. Soup Kitchen

Hi Joan,
Advil will help and should not increase the effusion. Indocin
(indomethacin) would be still more effective, but it's by prescription only
because it can be a little hard on the stomach, so check with your doc.
Best of luck resolving this,
Richard R

Basic research at the Max Planck Institute of Biochemistry leads to a
novel cancer therapy
Axel Ullrich, at the Max Planck Institute of Biochemistry in
Martinsried, Germany, already showed at the beginning of the 1990s that
blocking blood vessel development in a tumour slows down its growth, and
shrinks its tissue.
This fundamental principle led to the development of Sutent ( Sunitinib
).
When particular growth factors are bound to specific receptors on the
surface of a cell, this can cause the cell to propagate itself and build
certain tissue similar to blood vessels.
Worldwide, research into receptors has focused on a special class of
proteins, called tyrosine kinases. They are responsible for causing the
received signal to be transduced through a long signalling cascade into
the nucleus, triggering cell division and multiplication.
Signalling cascades are absolutely necessary, if various tissues - like
blood vessels, nerve tissue, and connective tissue - are to be built up
during the development of an organism and in the process of tissue
regeneration.
Research has focussed on these tumour cell signalling cascades, because
in cancers they are often disturbed. If there were a way to block growth
factors, or the receptors on the cellular surface from tumour cells,
that could lead to targeted therapies against cancers. Already in the
1980s, cancer researcher Axel Ullrich, then a scientist at Genentech (
USA ), working with colleagues in the UK and Israel, succeeded in
describing the structure and function of a receptor for epidermal growth
factor ( EGF ). Since then, tyrosine kinases and various growth factors
have been at the focus of research and development of therapies against
tumours.
Also, over a decade ago, a team led by Ullrich discovered that by
interrupting the oxygen and nutrient supply to tumour cells, it is
possible to inhibit cancer development. The Max Planck scientists showed
that tumour tissue just a few cubic millimetres in size can create
vascular endothelial growth factor ( VEGF ), which triggers blood vessel
development.
There is a receptor specific to VEGF, called Flk-1/VEGFR2, found only in
endothelial cells which are the building stones of new blood vessels.
When Flk-1/VEGFR2 is made inoperative, this blocks the development of
tumours. If no blood vessels are created in tumour tissue, the tumour
fails to grow. This discovery led to the invention of what are called
angiogenesis inhibitors.
Ullrich and the Max Planck Society, in co-operation with New York
University, founded Sugen, Inc. in California in 1991.
Sugen is the first biotechnology company with roots in the Max Planck
Society.
The firm developed chemical substances which block Flk-1/VEGFR2 in
endothelial cells.
At the end of the 1990s Sugen was taken over by Pharmacia, which itself
was bought by Pfizer in 2003. Development of the project continued at
Pfizer.
Sutent ( Sunitinib ) has now reached the market as a multi-targeted
tyrosine kinase inhibitor, which blocks both the building of blood
vessels in tumours as well as other illness-related enzymes in tumour
cell signalling networks.
Clinical studies with GIST patients looked into their ability to
tolerate Sunitinib, as well as its effectiveness on them.
Some of these patients had already been treated with Imatinib (
Gleevec/Glevec ), but their tumours continued to develop.
Others were not able to tolerate Imatinib at all.
Still other patients had advanced renal cell carcinoma with failed
available treatment.
In the case of the GIST patients, it took four times longer for tumours
to renew growth when treated with Sunitinib, compared to the placebo
group.
Patients with advanced renal cell carcinoma saw a shrinking of the
tumour; in 26 to 37 percent of them, the tumour shrunk to at least half
its size.
Sunitinib is being tested now, as well, on patients with advanced forms
of bladder cancer, breast cancer, cervical cancer, colon cancer,
esophageal cancer, head and neck tumours, liver cancer, lung cancer,
melanoma, ovarian cancer, pancreatic cancer, prostate cancer, and
testicular cancer. The studies are in various stages of clinical trials
( phases I through III ), and most of them are being carried out in
combination with other therapies.
Source: Max-Planck-Gesellschaft, 2006
XagenaMedicine2006

""a novel form of fluid retention presenting as multiple joint effusions
in a patient with advanced phase CML on high-dose imatinib, as well as
successful measures that were undertaken to control this adverse
event.""
Eur J Haematol. 2006 May;76(5):444-6. Epub 2006 Mar 17.
Multiple joint effusions associated with high-dose imatinib therapy
in a patient with chronic myelogenous leukaemia.
Moore JC, Dennehey CF, Anavim A, Kong KM, Tiong Ong S.
Division of Hematology and Oncology, College of Medicine, University
of California at Irvine, CA, USA.
Imatinib mesylate is a small molecule tyrosine kinase inhibitor that
has significant efficacy in the treatment of chronic myelogenous
leukaemia (CML). However, it is likely that patients with CML will
require prolonged and perhaps life-long therapy. In general, the
side-effects of imatinib therapy have been mild to moderate, with the
large majority of patients tolerating prolonged periods of therapy.
However, a minority of patients are completely intolerant of therapy,
while others are able to remain on therapy despite significant
side-effects. Here, we describe a novel form of fluid retention
presenting as multiple joint effusions in a patient with advanced phase
CML on high-dose imatinib, as well as successful measures that were
undertaken to control this adverse event. Although fluid retention,
including periorbital oedema, pleural and pericardial effusions, as well
as life-threatening cerebral oedema have been previously described and
attributed to imatinib, this is the first case of imatinib-associated
polyarticular effusions that we are aware of. Further work will be
required to confirm a casual relationship between imatinib therapy and
this novel side-effect, as well as to determine the underlying
pathophysiologic mechanisms.

Hi Joan,
I have not followed your story but have some suggestions, as I had a
pleural effusion with Gleevec early on. It was actually a pleural effusion
and pericarditis (heart also) combined but the pleural effusion was the
worst part I believe. I was hospitalized for a couple days because I had so
much pain....and put on pain meds (morphine) but mostly IV
anti-inflammatories to settle things down. I was told that the lining of
the lungs (pleural sac?) was irritated. I did have 800cc of fluid taken
from the left lung, and I don't remember a lot of pain after that, but I
was still off work for about a week or so.
You might need a stronger Rx anti-inflammatory.....as an over-the-counter
you might try Aleve, and you could take 2 pills twice a day for a good dose
(but run all this by whoever is treating you for this). Aleve is the Rx
drug Naprosyn.
For me, position was really important.....but this was more for the heart
involvement I believe. It felt better to lean forward, or lie on the left
side (because of the position the heart was in).
To minimize chest expansion, try to breathe from your belly (diaphragm).
Belly moves in and out when you breathe this way. Also, you could see if
binding your chest helps......try wrapping a towel tightly around your
chest, to minimize movement (like you would with a rib fracture)....if this
helps, you can get a 6 inch ace bandage to do this or use a strip of cloth,
etc.
Experiment with heat or ice and see if either helps with the
discomfort...they will also increase circulation which might help the
healing process.
Hope some of this helps you a bit. But if you remain really uncomfortable,
bug your doctor so he will address it. I was off Gleevec for 17 days during
this episode.
Nancy C.

Hi all,
I am still suffering from the pain of the effusion. I took a steriod
for 6 days it helped, but now the pain has returned with vengence.
Please if someone could offer some tips as to what they did. Also how
long can this go on? Dr. Said I have some fluid left , but not a lot
like before. Also he put me back on Gleevec 400mg increase to 600mg in
a week. Any home remendies someone said walking? Advil helps some, but
does that cause more fluid? Help??
Take care,
Joan P
dx'd 8/03
#662
400mg

Another use for Imatinib in the works.
Zavie
""Platelet-derived growth factor (PDGF) has been proved to play an
important role in progressive glomerular disease of systemic lupus. The
present study investigated the tyrosine kinase inhibitor of PDGF
receptor, imatinib, as a novel therapeutic approach for the cure of
lupus nephritis in New Zealand Black/White (NZB/W)F1 hybrid mice with
established disease""
""findings of amelioration of animal survival and renal manifestations
in NZB/W lupus mice with established disease by imatinib suggests the
possibility to explore whether imatinib may function as steroid-sparing
drug in human lupus nephritis.""
2006 May 10;
Imatinib ameliorates renal disease and survival in murine lupus
autoimmune disease.
Zoja C, Corna D, Rottoli D, Zanchi C, Abbate M, Remuzzi G.
1Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Platelet-derived growth factor (PDGF) has been proved to play an
important role in progressive glomerular disease of systemic lupus. The
present study investigated the tyrosine kinase inhibitor of PDGF
receptor, imatinib, as a novel therapeutic approach for the cure of
lupus nephritis in New Zealand Black/White (NZB/W)F1 hybrid mice with
established disease. Two groups of NZB/W mice (N=30 each group),
starting at 5 months of age, were given by gavage vehicle or imatinib
(50 mg/kg b.i.d). Fifteen mice for each group were used for the survival
study. The remaining were killed at 8 months. Imatinib significantly
(P=0.0022) ameliorated animal survival with respect to vehicle. The drug
significantly delayed the onset of proteinuria (% proteinuric mice, 7
and 8 months: 33 and 47 vs vehicle, 80 and 87, P<0.05) and limited the
impairment of renal function. Imatinib protected the kidney against
glomerular hypercellularity and deposits, tubulointerstitial damage, and
accumulation of F4/80-positive mononuclear cells and alpha-smooth
actin-positive myofibroblasts. The abnormal transforming growth
factor-beta mRNA expression in kidneys of lupus mice was reduced by
imatinib. In conclusion, findings of amelioration of animal survival and
renal manifestations in NZB/W lupus mice with established disease by
imatinib suggests the possibility to explore whether imatinib may
function as steroid-sparing drug in human lupus nephritis.

Hello Folks,
Dr. Goldman was in town today and gave met with fellow CMLers from Montreal,
Ottawa and Toronto.
He covered the basics of CML up to what is the current state-of the art.
Novartis also allowed him to announce the new brand name of Nilotinib -
Tasigna.
We will cover the more salient points of the talk in another e-mail.
It was nice to get together again with fellow CMLers and know that everyone
is doing well.
Cheers,
Cheryl-Anne

Hi Cheryl-Anne,
Now we have a musical little trio.....Gleevec, Sprycel and Tasigna!
tra-la-la-la-la
But of course, we are really fortunate to have all this research going on
and new drugs being developed. Looking forward to your notes from Dr.
Goldman's talk.
Nancy C.

Dane,
It's very good to hear from you!
I am sorry you had to battle the GVHD but from what I know it's sometimes
very important that this occurs and hopefully your good results only get
better.
Keep the faith... and stay strong:)
Lisa Martinez
Tampa
Message 6
From: "Dane T." dane714@...
Date: Tue May 23, 2006 6:19pm(PDT)
Subject: Good News from Houston!
Have not updated in a while, primarily because I have been feeling awful
from the side effects of the steroids I am on to treat Graft Versus Host
Disease. It has been a very difficult 3 months.

My mum is having shoulder pain, too. But , what kind of abnormality they see in
X rays??
http://spaces.msn.com/anabu36spain/

Dane,
Congratulations for the excellent news! Thanks for sharing and I hope that
things continue to get better and better.
Hugs,
Dana
"Dane T." <dane714@...
Have not updated in a while, primarily because I have been feeling awful
from the side effects of the steroids I am on to treat Graft Versus Host
Disease. It has been a very difficult 3 months.
I have started weaning off the drug (Medrol) in small increments, hoping the
GVHD does not return. So far, so good and tomorrow I will be down to only 8
mgs a day. I am slowly starting to feel my energy coming back, but still
quite debilitated from the muscle wasting in my legs, which is a common side
effect of the Medrol.
It appears that the plan to induce Graft versus Host Disease (via a high
dose Donor Leukocyte Infusion) in order to spark my immune system into
fighting the residual cancer cells (Graft Versus Leukemia) may be working.
My test results from May 9th came in and shows that I am once again 100%
Donor Cells and my BCR-ABL count (cancer cell count) has gone down from 8.32
in January to 0.13 as of May 9th.
This is the best possible news I could get at this point.
I return to Houston on June 15 for a bone marrow biopsy and with any luck
those results will show a continued trend for the better.
Regards and Prayers
Dane Tessler
www.caringbridge.org/tx/dane
www.danesweb.com
SPONSORED LINKS
Individual medical
Cml Leukemia
Health professional Cancer center

From Chattanooga, Tennessee, through British Columbia and Yukon, to
Alaska and around the Western and South Western USA states, approx
15000 miles and two months in the motorhome.
Anyone who has CML and would like their name written on the side of
our motorhome for the ride please send me an email:
livingwithcml@... with your first name and initial of your
last name. If you would feel comfortable sharing a bit about who
you are that would be great, but only if you chose to do so. I love
reading everyone's stories it gives me strength.
The Leukemia & Lymphoma Society has given us permission to use their
logos on the motorhome for this fundraiser - hopefully we can get
that done soon. We have plenty place for your names and will keep
adding them as long as we can see out of the windows :-) This trip
across country is in an effort to raise funds for the LLS.
This adventure is for all of you too it's because of you that
Steven has a really good chance at life. You have laid the
groundwork for Steven by going through the trials, the years with
CML, sharing your stories and surviving the hard times and showing
us that there are good times too. If you are newbies, like us, then
you need the ride anyway to ease this round of stress any reason
to "ride the road" is good for me!
You have all given me so much strength, hope and helped keep me sane
and able to sleep at night and we would be really honored to have
you on the road with us
Love and Thanks
Annie
(mom of Steven)
www.livingwithcml.blogspot.com
www.roadrunnersusa.blogspot.com

Hey Group:
CONGRATS . . . Judy. . . You Go Girl! ! ! I keep you in my prayers as my
'heroine'. You have survived pre 'our gold' came full circle. . . and still you
rise to "0"! "RAH, RAH, RAH". (cymbals & pompoms).
Dane. . . praying for your maintenance of Donor cells!
Prayer for Newbies adjustment to our gold and survival. Dr Drucker stated at
the ASH Conference that our bug~CML is a CHRONIC disease; and a newly diagnosed
survivor has a 25 year median. . . complete opposite to the morbid mortality
rate I was given almost 3 years ago.
As I tell everyone 'I AM FANTASTIC' . . . all of you, my sister & brother
survivors are also "FANTASTIC". . . and as always; in my prayers.
"K"
"I AIN'T FINISHED YET"!!!

Hi Nanc, I'm back home after an extended stay with my sister. Just
going through some posts and saw your "fish" news. I'm so happy for
you. Fingers crossed that the cyto will show a drop as well. This
has been a long time coming, I hope you're feeling well. Ellen

Dane I'm so glad to hear about the good news you received. I'm sorry
this has been such a long hard road, but I hope you continue to scale
that mountain. Prayers, love, and hope.
Amy B.

Have not updated in a while, primarily because I have been feeling awful
from the side effects of the steroids I am on to treat Graft Versus Host
Disease. It has been a very difficult 3 months.
I have started weaning off the drug (Medrol) in small increments, hoping the
GVHD does not return. So far, so good and tomorrow I will be down to only 8
mgs a day. I am slowly starting to feel my energy coming back, but still
quite debilitated from the muscle wasting in my legs, which is a common side
effect of the Medrol.
It appears that the plan to induce Graft versus Host Disease (via a high
dose Donor Leukocyte Infusion) in order to spark my immune system into
fighting the residual cancer cells (Graft Versus Leukemia) may be working.
My test results from May 9th came in and shows that I am once again 100%
Donor Cells and my BCR-ABL count (cancer cell count) has gone down from 8.32
in January to 0.13 as of May 9th.
This is the best possible news I could get at this point.
I return to Houston on June 15 for a bone marrow biopsy and with any luck
those results will show a continued trend for the better.
Regards and Prayers
Dane Tessler
www.caringbridge.org/tx/dane
www.danesweb.com

note was cut short.
Nancy C.

Congratulations Judy.....I know this is a big relief to get back to ZERO!
It is so nice when we have 'other' options when our disease is not controlled.
Maybe Zavie will send you some info on how to add a note to the Dr. Druker
appreciation album from Gleevec........if you hav

Hi Judy -- What good news! Thanks for sharing and best wishes
always, Kathy

Hello All,
We are so fortunate to have Dr. Goldman visit us tomorrow.
Here are some instructions for tomorrow's Lunch & Learn with Dr. Goldman.
Please share this message with other CMLers who may want to attend
LUNCH: The lunch will actually take place in the main cafeteria of the
Royal Victoria Hospital - the 3rd floor. It has been completely renovated
and we have our own private room. Lunch is a "Gourmet" box lunch which has
an assortment of sandwiches, veggies, fruit and juice and water. We only
have 1/2 hour for lunch as we should start the lecture at 12:00 sharp.
LECTURE with Q&A: Will be held in the Primrose Amphitheatre which is
located in the Woman's Pavilion room F3 10. It is quite easy to get there
from the 3rd floor cafeteria. We will take the elevators located past the
patient elevators on the third floor and go up to the eight floor. We
follow the corridor and go right just before the Ross Pavilion Café and walk
down to the Primrose (if you haven't finished your lunch, you can bring it
with you).
PARKING: Parking is just crazy these days at the Royal Victoria. Wear
comfortable walking shoes. We cannot use the doctors parking this time as
it will be completely full. We will have to go in by P3 and more than
likely we will have to park up on P7. It offers a lovely view of Montréal
as it is actually located on the mountain, however it is a bit of a walk to
the building. If you wind up in P7 take the stairs at the far end of the
parking down past the pool, go left and walk up the slight incline towards
the woman's pavilion. Go in by the woman's pavilion, and go right, take the
stairs one flight down and follow the corridor to the elevators (you'll walk
past the Primrose Amphitheatre) and take the elevators to the 3rd floor.
If you would like my cell phone number, please get in touch with me and I
will give it to you. I will leave my cell phone on (shh, don't tell anyone)
to help you if you get lost.
The lecture must start at 12:00 sharp and finish at 13:00 sharp as Dr.
Goldman must go to another talk with doctors at another hospital. I will be
taking him there.
If you haven't yet confirmed your attendance with me, please let me know
today so that I can make sure we have enough food.
See you all tomorrow.
Love and Peace,
Cheryl-Anne

Here is some advice to plant some flowers and go for a walk!
Influence of yard work and weight training on bone mineral density among
older U.S. women.
Turner LW, Bass MA, Ting L, Brown B.
Department of Health Science, Kinesiology, Recreation and Dance, 309 HPER
Building, The University of Arkansas, Fayetteville, AR 72701, USA.
lori@...
The purpose of this study was to determine the influence of type of
physical activity on bone mineral density among older U.S. women. Findings
from the present study indicate that jogging, swimming and calisthenics
were weak predictors for high bone density values. Bicycling, aerobics,
walking and dancing were moderate predictors for positive bone density.
Yard work and weight training were strong and independent predictors for
positive bone density.
PMID: 12537080 [PubMed - indexed for MEDLINE]

I have some news I want to share with the group. For the new people, I was
diagnosed with cml in 1992, had a bone marrow transplant in 1993 and relapsed in
2004. Since then I have been on 400mg of gleevec and after some initial
problems have been doing very well. I had a bmb on 9th of May and was due to
see my doctor for results next week. He left a message on my phone today to say
the results of the pcr are in 0.00% . At relapse I was 85% so I am absolutely
thrilled with this outcome. I guess from the decimal points this will be
looking at 10,000 cells, but I'm not sure, will findout next week, but after
being in remission so long before I feel like I've won the lottery again. I
wanted to share my news with you all and thankyou for all the help and advice
you have given me. I particularly wanted to mention how much Zavie has
supported me, I met him just after relapse when I was very frightened and felt
very alone, his wisdom and positive attitude has helped me
through some very dark days and nights, and his chat line has been a great way
to share this journey we are all on.
Judy Telford

Hi "K" and others,
On my last visit with Dr. Druker, I showed him the abstract about the bone
issue with Gleevec. He looked at it briefly, was aware of it and said that
the way the study was done was not very scientific....that just because 2
things happen, in an aging population, it does not mean that one causes the
other.
That said....he did say that when you have CML, your bone x-rays will not
be normal....this is before treatment and while on treatment. So, when an
orthopedist sees something on x-ray and is concerned....it may really be a
normal CML x-ray. I know from others who write on various lists that they
have had doctors concerned about X-rays (looking like cysts or tumors or
???) and have been told by Dr. Talpaz that it is nothing....so he is saying
the same thing. So if you have something like shoulder pain and see an
orthopedist who takes an X-ray and expresses some concern.....it is best to
have a CML specialist look at the X-ray (it may just be a 'normal' CML
abnormality).
Maui Nanc

Hey Alicia & Christine & Group Regarding Bone Pain:
I have been told that its unrelated, but I had numerous Chronic Orthopedic
Diseases pre our bug~CML. I actually have OsteoNecrosis, which is 'bone death
disease'. None of the Doctors will link any of my diseases to our bug.
I've had 3 hip surgery's, and in need of 4-5 Orthopedic Surgery's at the
present time; but the 3 Ortho Surgeons said 'bye' and put me in Pain Management
because they didn't want their reputations tarnished. . . performing major
operations on me.
My common sense tells me that they use bone marrow in diagnosing our disease,
and we have some bone pain(hmmm). I know that my pain level has increased in the
3 years I have been a survivor(hmmm). Our immune system, bone marrow, and blood
are all involved(hmmm); but my Oncologist, & 3 Ortho Surgeons say that they
aren't related. Go figure. . .
I am on 'what they call heavy medications' for my Chronic Pain and will be for
life. Make sure that your doctor gives you something other than Percocet for
your pain because of the Acetaminophen in this medication; which is detrimental
to the liver. Percodan is stronger, and uses Aspirin. Vicodin works for minor
pain. As with any medication, start with the lesser dosage. I have been up &
down with pain medications since the early '90's; and with my Chronic Orthopedic
Diseases. . . all of which I call Chronic Illnesses. I am never pain-free and
will have to take the medication for life.
Take care Group. . . and know that I have all in my prayers.
"K"
"I AIN'T FINISHED YET"!!!

Hey Nancy. . . CONGRATS!!!! I have been saying Xtra prayer for you.
"K"
"I AIN'T FINISHED YET"!!!

Chat Reminder - Saturday 9:00 AM EDST
Photos - Canadian Liberator Tulips - Ottawa - Gift from Holland

Hey Nancy,
I replied under another subject heading, and you may have missed it!
CONGRATULATIONS! This is one downward trend that we all hope
continues for you!
Love and all good things,
Cheryl-Anne

Hello CML buddies,
I read that Oil of Olay is working with over 1000 dermatologist's
offices to offer FREE skin cancer screenings throughout May and June.
Since we are all suspectible to skin cancer, especially because of
Gleevec inhibiting C-Kit, I thought this was worthwhile to post.
Go to www.olay.com for the dermatologists that are offering this
service in your state.
Sincerely, Lynn (Snickersunny)
Dx'd 12/03
PCRU
400 mg Gleevec

Hello CML buddies!
Has anybody written to or spoken to a CML expert regarding this
latest study, and/or if they are going to broaden this study?
Should we all be getting periodic "Serum Phosphate" monitoring with
this news...and also possibly Bone Density screenings... or at least
a baseline? Maybe they will discuss at the next ASH possibly...?
This is very important news. I wanted to ask Dr. Nimer about it
during the CML teleconference today, but was not able to get through
the telephone lines..
Did anybody listen to it? I thought that it was an excellent RECAP
about CML basics and spoken in an easy,layman fashion-very through.
My only wish would be that they gave it more time. An hour is not
enough time to cover such a broad scope. Plus, they always ask
people to keep their quesitions "broad" in nature, and it always
turns out to be a personal consult..
Sincerely, Lynn (Snickersunny)
DX'd 12/03
PCRU
400 mg Gleevec.

Title: The Changing Horizon:
Managing the Challenges of CML Treatment
SPEAKER: STEPHEN D. NIMER, MD
DATE: Thursday, May 18, 2006
TIME: 12:00 PM to 1:00 PM Eastern
11:00 AM to 12:00 PM Central
10:00 AM to 11:00 AM Mountain
9:00 AM to 10:00 AM Pacific
DIAL-IN NUMBER: 888-633-9557
PASSWORD: "Education"
Conference ID: 7329281
Please remember to dial-in 15 minutes prior to start time.
Photos: Tulips in Ottawa
Zavie

http://www.docguide.com/news/content.nsf/news/852571020057CCF68525716F00
44422B
New Study Shows Initial Treatment With 800 mg/day Imatinib Mesylate
(GLEEVEC) Significantly Improved Progression-Free Survival in Group of
High-Risk Patients With Rare Form of Gastrointestinal Cancer
. Investigation of high-dose Gleevec regimen significantly reduces
relative risk of progression by 61% in patients with specific mutation
. Authors recommend these patients receive 800 mg/day at start of
therapy
EAST HANOVER, GERMANY -- May 15, 2006 -- A higher, investigational
starting dose of GleevecR (imatinib mesylate)* tablets can improve
outcomes for high-risk patients with advanced Kit-positive
gastrointestinal stromal tumor (GIST) expressing exon 9 mutation,
according to new findings from the largest clinical trial to evaluate
the drug's effects by mutation. The study findings are now available
online and are expected to be published in May.
The clinical trial, an EORTC (European Organisation for Research and
Treatment of Cancer) phase 3 study, compared two doses of Gleevec in
patients with unresectable and/or metastatic Kit (CD117) positive GIST.
While the majority of patients derived benefit from taking 400 mg/day of
Gleevec, the study showed that patients whose tumors expressed a
mutation on a certain gene segment called exon 9 had significantly
superior progression-free survival (P =.0013) when administered Gleevec
at the investigational dose of 800 mg/day.
"This latest study provides further evidence that Gleevec is a highly
effective therapy for patients with advanced Kit-positive GIST, and
offers insight into potential ways to improve long-term outcomes for
these patients," said Diane Young, Vice President and global head of
Clinical Development at Novartis Oncology. "These data also highlight
that the investigational dose of 800 mg/day may be more effective for
high-risk patients expressing the exon 9 mutation."
In this study, investigators analyzed data from a recent randomized
EORTC Phase III trial comparing two doses of Gleevec (400 mg/day vs. 800
mg/day) in patients with unresectable and/or metastatic Kit-positive
GIST, to assess whether tumor genotype correlated with the
dose-dependent clinical response to Gleevec. Pre-treatment samples of
GISTs from 377 patients enrolled in the clinical trial were analyzed for
mutations of Kit and platelet-derived growth factor receptor alpha.
The presence of a Kit exon 9 mutation was the strongest adverse
prognostic factor for response to Gleevec, increasing relative risk of
progression by 171% (P <.0001) compared to Kit exon 11 mutations. In
patients whose tumors expressed a Kit exon 9 mutation, treatment with
the high-dose regimen resulted in a significantly superior
progression-free survival (P =.0013), with a reduction of the relative
risk of 61%.
About Gleevec Tablets
Gleevec (imatinib mesylate) tablets are indicated for the treatment of
patients with KIT (CD117)-positive unresectable and/or metastatic
malignant GIST. The effectiveness of Gleevec is based on objective
response rate. There are no controlled trials demonstrating a clinical
benefit, such as improvement in disease-related symptoms or increased
survival.
Important Safety Information1
Severe (NCI Grades 3/4) lab abnormalities (400mg/day; 600mg/day) --
including neutropenia (10%; 11%), anemia (3%; 9%), and hepatotoxicity
(6%; 8%) -- and severe adverse experiences (NCI Grades 3/4), including
fluid retention (eg, pleural effusion, pulmonary edema, and ascites) and
superficial edema (7%; 12%), hemorrhage (6%; 11%), and musculoskeletal
pain (6%; 1%), were reported among Gleevec patients. Patients should be
weighed and monitored regularly for signs and symptoms of edema, which
can be serious or life-threatening. There have also been reports,
including fatalities, of cardiac tamponade, cerebral edema, increased
intracranial pressure, papilledema and gastrointestinal perforation.
Bullous dermatologic reactions (eg, erythema multiforme and
Stevens-Johnson syndrome) have also been reported. In some cases, the
reaction recurred upon rechallenge. Several postmarketing cases note a
resolution or improvement of bullous reaction following dose reduction
with or without supportive care.
Some patients (5%) were reported to have severe GI bleeds or
intratumoral bleeds. GI tumor sites may have been the source of GI
bleeds.
Dose adjustments may be necessary due to hepatotoxicity, other
nonhematologic adverse events, or hematologic adverse events. Therapy
with Gleevec was discontinued for adverse events in 8% of patients at
both dose levels.
Patients with severe hepatic impairment should be treated at a starting
dose of 300 mg/day and should be closely monitored.
Gleevec is metabolized by the CYP3A4 isoenzyme and is an inhibitor of
CYP3A4, CYP2D6, and CYP2C9. Dosage of Gleevec tablets should increase by
at least 50% and clinical response should be carefully monitored in
patients receiving Gleevec tablets with a potent CYP3A4 inducer such as
rifampin or phenytoin. Examples of commonly used drugs that may
significantly interact with Gleevec include acetaminophen, warfarin,
erythromycin, and phenytoin. (Please see full prescribing information
for other potential drug interactions)
For daily dosing of 800mg and above, dosing should be accomplished using
the 400mg tablet to reduce exposure to iron.
Use of Gleevec tablets is contraindicated in patients with
hypersensitivity to imatinib or to any other component of Gleevec
tablets
Women of childbearing potential should be advised to avoid becoming
pregnant while taking Gleevec tablets
Because of the potential for serious adverse reactions in nursing
infants, women should be advised to avoid breast-feeding while taking
Gleevec tablets
Common Side Effects1
The majority of patients who received Gleevec in the clinical study
experienced adverse events at some time. Most adverse events were mild
to moderate in severity. The most frequently reported adverse events
(all Grades, 400mg/day; 600mg/day) were superficial edema (81%; 77%),
diarrhea (59%; 70%), nausea (63%; 74%), fatigue (48%; 53%), muscle
cramps (47%; 58%), abdominal pain (40%; 37%), rash (38%; 53%), vomiting
(38%; 35%), musculoskeletal pain (37%; 30%), and hemorrhage (26%; 34%)*
Supportive care may help the management of most mild to moderate adverse
events so that the prescribed dose can be maintained whenever possible
Gleevec tablets should be taken with food and a large glass of water to
minimize gastrointestinal (GI) irritation. Gleevec tablets should not be
taken with grapefruit juice.
* Known as GlivecR (imatinib) outside the U.S.
* Numbers indicate the range of percentages in 5 studies among adult
patients with Ph-positive CML and KIT-positive GIST. For more detailed
study information, please see the full prescribing information for
Gleevec.
SOURCE: Novartis Pharmaceuticals Corporation

Dear Giora,
I am sorry to hear about Dot's stroke. We are praying for her. She
has been an inspiration and advocate for so many.
Strokes are so scary.... My Mom's BP has recently been out of control
268/139!!! She went to emerg and we thought she was going to have a
stroke but she did not. She is on hypertension meds now and the BP is
slowing coming down...nerve wracking stuff.
Peace, love and everything good,
Christine

Hi Nancy,
I accidentally sent a message meant for you to Zavie and Cheryl Anne. Please
check it out It's about your FISH.
Susan

Hey Nancy,
Just home from work and doing another scan of e-mails. Found yours of earlier
today. So the FISH finally got the message from the turtle to get outta town,
huh? Wonderful news. Looking forward to the cyto results.
Love,
Susan

Hi Christine,
My cyto and FISH has always been right in line with each other....at 3
months, cyto was 30% and FISH was 26%. (At the start of the trial, my cyto
was 35% and I think FISH was 32%).
So, Dr. Anthony might be right on the $$$ with NAET........at 20%.
When Dr. D said I might be a dasatinib turtle it did not even register,
because 'we' use that term all the time.......later, I thought, 'hey, what
does he know about turtles'.
Anyway, it feels good to see some downward movement.
We can do the turtle strut across the zero line together! (and I think we
will be some of Zavie's longest hold-outs!
love, Maui Nanc

Hey Nanc,
17%!!!!!!!!!!!!!! That's terrific!! I hope you see a drop in the
cyto too. I waiteed 12 months to get a response so I hope your
response at 6 months is taking you to zero by 12!
Yipppeee... another turtle closing in on the zero line.
I love that Dr. D. knows you are a turtle. :-)
Much love,
your turtle pal,
Christine

Dear Giora,
Wishing Dot a 'refuah shleima'.
Dot and Leo became dear friends during the STI571 trials at OHSU.
Zavie

Thanks Richard..........
Yes, the FISH was just the preliminary, I only had my bma last Thurs. We
will get cyto %, FISH and pcr. I have been stuck at 30-35% for about 3
years, so this is looking like a change.
This Sun. I am going to one of Ian's concerts.....they do a really good
job. Also a chance to bump into Carrie and John.
Love you, and thanks for caring about all of us on the list.
Maui Nanc

Hooray for you Nancy - I'm so happy to hear that your FISH is taking the
plunge at last! Keep going - deeper, deeper!
Love,
Richard R
PS - are you tracking PCR as well?

Yes Chris, I do. Have been fighting it for 3 years. On Gleevec, 400mgs, and
bone pain can be a 10 (scale 1-10) at times, like today when weather is cold,
raining. Have you mentioned it to your doctor? - Lynne A.

Hi Richard,
Thank you for adding your knowledge. Many years ago during an especially
stressful time (as now) I had the same sensation which finally went away. I
think you're right. When I'm actively busy it is less and when I'm quiet or
inactive it gets worse.
Thanks again.
Love,
Susan

does anyone else out there ever have severe bone pain in the femur? I have it
at times so that it feels almost debilitating. Have taken to using a cane at
times. Also, severe pain in the ribs on one side?
chris in minn
dx 12/03/03
remission 06/04
gleevec 4oo daily

Hi Jane
You know that caravan park on the left hand side of the road going
into Stellenbosch? I started that one! Mountain Breeze. I mostly
lived in the Southern Suburbs though. Been here since 94.
Steven is doing great - what a wonderful attitude this 'child' has -
no "siestog" with him! (another form of 'shame')
You can email me directly if you want to chat SAfricanese........ :-)
Love and light
Annie
www.livingwithcml.blogspot.com
www.Roadrunnersusa.blogspot.com

Hi Susan,
The sensation you describe is almost certainly a variant of
hyperventiallation due to stress, especially in light of normal O2 levels
and xrays. A normal pulmonary function study result would clinch the
diagnosis, but I don't think that's necessary.
If you're meditating these days, you might see whether the symptoms change
after you're done (though it wouldn't be surprising if they actually
increased the early part of a sit; as you become more conscious of your
stress, its symptoms seem to increase before you're able to let them go).
Warm regards,
Richard

It is a dual kinase inhibitor, much like Bristol's MBS-354825 (also known as
dasatinib).
Dual inhibitors are supposedly stronger than Gleevec.
To find out more just type SKI-606 in any search engine and you will find
lots of information about it.
Regards,
Mario
_____
From: kathydf47 [mailto:kathydf47@...]
Sent: Tuesday, May 16, 2006 9:37 AM

Anyone have any info on this CML drug? A friend is being advised by
MDACC to start it & I had never heard of it. thanks for any help.
best to all,
Kathy
dx 5/03

Hey Annie
Your statement about the Universe really made me laugh - I am MUCH
more circumspect now! Whereabouts in CT are you from? We are in
Somerset West. How long have you been in the States? How's your
son doing? - he is so young to be dealing with this. Shame!
Thought the use of that good old South African word will warm your
heart. For the rest of you - "shame" in South Africa can mean
anything from "poor thing" to "isn't he cute?" Weird country this.
Regards
Jane

i am very sad to report that dot is in very bad health right now. she had a
stroke about 9 days ago and is in coma at the hospital. it is so sad that
someone who had been fighting cml for so many years and so bravely is suffering
from an unrelated sickness.
dot has been the main idea and founder of our israeli cml patients support
group.
i hope that she will recover soon with the help of your prayers
shalom
giora

Notre Dame Cathedral with Loiuse Bourgois's spider sculpture in the
foreground, Ottawa, Canada.

Hi Cheryl-Anne,
I realized that I did not write that exactly correctly...about Dr. D
worrying. I don't think it was about me personally.........but collectively
for ALL us cmlers. That it is his worry or concern, that these drugs are
not killing off all the cml cells.....he is a problem solver and he has
taken this on as his problem to solve! I did remind him that I was doing
'other stuff' for my cml and he said......"yes, I know"
also NEWS FLASH...........I just got my preliminary FISH for my 6 month on
BMS. I don't have my results from the 3 month right in front of me (but
cyto was unchanged at 30% and FISH was sl. down at 26% I
think)..........................
my preliminary FISH is down to 17%............the dasatinib turtle might be
on the move! Actually I was anticipating this.......because I brought a
sample of bm aspirate home in a vial (Dr. D is very co-operative about my
requests) and had my alternative practitioner test it (me holding it and
him asking questions, a form of NAET) and it said my results would be less
than 30%........and between 20-25%.........so we will see what cyto results
are!
that's all for now,
Maui Nanc

I am sure that cookies have a strong influence on the stamina that
researchers have! I call it my 'cookies for a cure' program.....and Dr. D
says those cookies disappear in a day! These folks in the lab, doing all
the tedious, repetitive work of research don't have much patient contact
(if any)......so it is a nice way to let them know that there are real
people out there benefiting from their research and appreciating them (I
think that appreciation goes a long way with with any employee). Along the
way I discovered those ?? silicone baking 'things' that you put on the
cookie sheet....so they don't stick and don't burn!! they work
great...never a ruined batch. I also gave them all my left-over Halloween
candy!!
Maui Nanc

Hi,
In response to your comments about research and big pharma and their agenda in
terms of a cure or more new disease management drugs instead: Nothing that Big
Pharma does that is self-serving would surprise me.
I'm going to be plying those researchers at hospitals with cookies and any other
sweets that might make them work with more vigor and independent minds.
Susan

Hi Susan,
Just to let you know, Dr. Goldman will be here doing a speaker tour
with most of the hem/oncs here in Montreal. This is why we had an
opportunity to have him speak to our group. He is quite excited to
meet us all as he is fascinated with patient groups. I am finding
that most hem/oncs out there (those in the know anyway) are checking
out the various lists and are impressed with the level of knowledge
we have.
My understanding is that Dr. Goldman is interested in immunotherapy
and I am looking forward to talking to him a bit about that when he
is here in a couple of weeks.
I have recently started back into gardening and I am enjoying it when
I can get to it. Good luck with your plants and let us know how it
goes.
Cheers,
Cheryl-Anne
results, I don't actually know what Dr. Goldman is researching at NIH
except that it's CML. He only sees a couple of patients one day a
week, too. Obviously, since Cheryl Anne was able to book him, he is
also making presentations to groups here and there which I'm happy
about because he's so good at explaining the disease and also because
he stays abreast of drugs, vaccines in the pipeline.
had a cold rain. But other days we have sun and it's in the 70s. I
prefer the latter, of course. Have a good time planning and planting
your garden. I have to satisfy myself with big pots of plants on my
second floor balcony but even that is fun and it looks so pretty when
they're all blooming in the summer.

Hi Nancy,
Yes, since this research center at the University oif Maryland has a wing (small
but well-funded, I think) dedicated to BMTs, I'm sure they're always looking for
candidates. Also, because stats from the procedure have been improving I'm sure
they'd love to get their handsa on a 60-year-old with no siblings. Yikes! No
thank you.
I also have a question for you which I have asked my trial doc and nurse
practitioner but no one has an answer yet. I have trouble getting full
satisfying deep breaths. It's like they stop just short of filling my lungs.
They took an xray that didn't show anything. And my lungs always test well --
full breaths, no fluid. Also, the oxygen levels in my blood are quite good.
Any ideas? I had this same pheno many years ago and it was stress. That
woulnd't surprise me at this point, but I sure would like to get rid of it!
Bests,
Susan

Hi Jane,
I also forgot to mention that the 2nd generation drug, dasatinib (the BMS)
drug is expected to be approved in June in the US....and that will
gradually start availability elsewhere??? I don't know the time frame or
process. Many who have switched from Gleevec to this drug in trials find
that the side effects are much less for them. So this might also be a
future option for you.
It is a more potent drug (so should work as well or better than IM) but has
fewer side effects.
And about the stress causing CML.......what stress does is decrease the
effectiveness of your immune system.......which might have played a part.
For 'some' reason, your immune system did not recognize your first cml cell
as 'defective' and eliminate it.
Best wishes,
Nancy C.

Hi Jane,
You should always bring your questions and concerns to the list....others
will share their knowledge and experience with you.
Some folks on Gleevec are able to work and others are not, and some of
those are on disability. Yes, the CML is under control....the disabilty
comes from the side effects of the treatment. You need to start a diary
documenting these on a daily basis for a record....
with some specifics. Like did you need a nap....what could you not get done
because of fatigue, etc. Even rate the side effects on a 5 point scale.
The thing for your disability analysts to realize.....when they think
remission, they think you have had treatment and are stable in remission.
Most other cancers have a course of treatment that stops. This is
different.....we keep taking the same drug that causes the side effects
every day....it does not stop! Tell them it is like having 'chemo therapy'
every day!
NO NO NO......you are not an ideal candidate for a BMT............because
of age, the fact that it would be an unrelated donor..........you chances
of dying from the procedure itself are at least 20% (more I am sure) and
all the possible complications like GVHD. And if you are having a good
response from Gleevec......why would you decide to play Russian Roulette!!
If you have doctors that are so keen to try a BMT......suggest that they do
one on a relative of theirs!! I do not believe that ANY cml specialist in
the US would be recommending a BMT to you......if you wanted one, that
would be your choice.
Yes, there are very good cml specialists in England. You might go onto the
European CML site and ask there about how you might get an appt.
That site is www.cmlsupport.org
If you simply wanted a statement with his opinion, in response to your
question (here is my brief history, my response to Gleevec.....should I
consider a BMT)..........Dr. Druker at OHSU is very good about replying to
e-mails................ drukerb@...
Keep in touch with the list.
They are good for a reality check....no one knows better what it is to be
dealing with CML than those who also have it.
Nancy C.
Eugene, OR.....patient at OHSU

Hello Jane
I am sorry about your diagnosis and hope you find a doctor that be
able to help you feel comfortable with your choices about BMT or not
and help you handle this disease.
My 22 year old son was diagnosed with CML in March this year and
this board and the

Hi there
Been lurking but not posting for a while. Mainly because I know I
have questions but I haven't been sure how to form them. Now I am
feeling really low so I am just gonna take a shot at it. So many of
you are so wise, I can only benefit huh?
During the whole oflast year I was fighting a horrible battle at
work which looked like it was going to end up in the labour court.
I got really stressed out in November and asked 'the universe' to
find a way for me toget out of the situation with a little money and
without having to go to court. Later that same week, I took myself
off to the doctor to deal with the "stress" symptoms and got the CML
diagnosis! Bummer.
Anyway, it now became a possibility to apply for disability benefits
and to leave the organisation that way so I stopped fighting my
employer and concentrated on fighting the CML.
The insurers are now suggesting that, because of Gleevec, the CML is
not a disability but something more like Diabetes and therefore I am
not disabled. Which, I guess, is probably true except that I am so
exhausted on the Gleevec that I can hardly do anything!
I am 47 years old, I have 3 kids and a husband and am under pressure
to go full steam ahead for a BMT. My gut is shrieking "NO" but the
doctors are really keen to try it. I do not have a sibling match.
I really need to talk with a CML specialist because the more I see
of my oncologist, the more I understand that her knowledge is
shallow. Also, she just doesn't have the skill to help me make my
case.
I live in South Africa and, to my knowledge, we don't have any CML
specialists here (unless one of you knows better) so I was wondering
if any of the amazing docs that you all talk about would be willing
to enter into an email conversation with me.
There is a chance that I may get the opportunity to travel to
England in September - are there any really good specialists there?
Another strange thing - a close friend and work colleague who has
also gone through the kind of work stress that I did and is also
fighting a legal battle has also been diagnosed with CML - do you
think that is at all significant?
I will be interested to hear your responses
Regards
Jane

It would be fun, but I'd better wait until summer. I come down on Tuesdays and
Thursdays for two classes.....the first is an eight o'clock and the second is at
twelve, then I have to scoot home to pick up my daughter. But let's plan on
something. When is the Art on the Vine that you were talking about last summer?
And wasn't today spectacular?!!! I have definitely worn a path between here and
Eugene.
I am keeping my fingers crossed for your six month results! rosemary