Gleevac

[Guest guest]

Does anyone have experience treating a patient w/ herbs who is also being treated w/ gleevac? The drug is still being researched and I’m unclear about interactions, side effects, ways to potentiate it’s effect, etc.

 

thanks!,

Cara

--

Cara O. Frank, R.Ac

herbbabe

China Herb Company

[Guest guest]

gleevac

>>>What is it?

alon

[Guest guest]

My patient has GIST.

gleevac, at this moment, looks to be the future of cancer treatments. He is having no side effects. (!).

 

Cara

 

 

FDA Approves Gleevec for Leukemia Treatment; Gleevec Also Produces Complete Remission in GIST Cancer

 

The cancer pill Gleevech as shown remarkable benefits for the treatment of chronic myeloid leukemia (CML), -- a rare, life-threatening form of cancer. The drug works by specifically targeting cancer cells, leaving most healthy cells unaffected.

 

The US Food and Drug Administration (FDA) last week announced the approval of Gleevec (imatinib mesylate, also known as STI-571) for CML. FDA reviewed the marketing application for Gleevec in less than three months under its " accelerated approval " regulations.

 

Gleevac Also Works Well for GIST Cancer

 

In a surprise announcement in San Francisco today [May 14, 2001], researchers told delegates to a meeting of the American Society of Clinical Oncology that Gleevec was also showing dramatic benefits among patients with another incurable form of cancer: advanced intestinal cancer gastrointestinal stromal tumor (GIST). The drug has produced complete remissions in more than 180 people with GIST who were participating in clinical studies in the US and Europe.

 

There is growing speculation that Gleevec may be useful in treating a wide variety of cancers. The National Cancer Institute has plans to initiate clinical trials of Gleevec against other types of cancers. The FDA has been inundated with calls about the drug's availability for the treatment of other cancers. Although Gleevec is FDA-approved only for the treatment of CML, physicians can legally prescribe the drug for " off-label " use, although patients would not receive insurance reimbursement for the prescription cost.

 

Gleevec costs $2,000-$2,400 monthly, and is expected to be available by prescription in US pharmacies by the end of May.

 

" FDA and Novartis, the drug's manufacturer, should be commended for the rapid development and review that will make this product available soon for the leukemia patients who desperately need it, " said Health and Human Services Secretary Tommy G. Thompson. " It is also important to recognize that today's approval is also a culmination of years of work and years of investment, by many people in many different institutions, and even in different fields of medicine. It's a testament to the groundbreaking scientific research taking place in labs throughout America. "

 

FDA approved the drug for treating patients with three stages of CML: CML myeloid blast crisis, CML accelerated phase, or CML in chronic phase after failure of interferon treatment. Accelerated approval allows FDA to approve drugs for serious or life-threatening illnesses on the basis of clinical trials establishing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a real clinical benefit. Gleevec has been shown to reduce substantially the level of cancerous cells in the bone marrow and blood of treated patients.

 

FDA approved Gleevec under FDA's orphan drug program which provides financial incentives for drugs developed to treat rare diseases.

 

" Although the long term benefits of the drug are not yet known, early studies have shown that Gleevec will offer a significant improvement for many patients, " said FDA's acting commissioner, Bernard A. Schwetz,PhD. " However, " he said, " further studies are needed to evaluate whether Gleevec provides an actual clinical benefit, such as improved survival, as well as to examine its effect when used in early stage disease. "

 

Dr. Schwetz also said that it is important for physicians and patients to understand currently known side effects from Gleevec, and to realize that additional side effects may be discovered with more follow-up of patients in ongoing studies. Side effects frequently reported in trials of Gleevec include nausea, vomiting, edema (fluid retention), muscle cramps, skin rash, diarrhea, heartburn, and headache. Severe fluid retention occurred in up to two percent of patients, and any unexpected and rapid weight gain should be investigated and, if necessary, treated.

 

Chronic myeloid leukemia occurs when pieces of two different chromosomes break off and reattach on the opposite chromosome, forming the so-called " Philadelphia " chromosome. This chromosome translocation leads to a blood cell enzyme being " turned on " all the time. As a result, potentially life-threatening levels of both mature and immature white blood cells occur in the bone marrow and the blood.

 

Gleevec, a specific inhibitor of the translocation- created enzyme, works by blocking the rapid growth of white blood cells.

 

" For the first time, cancer researchers now have the necessary tools to probe the molecular anatomy of tumor cells in search of cancer-causing proteins, " said Richard Klausner, M.D., director of the National Cancer Institute. " Gleevec offers proof that molecular targeting works in treating cancer, provided that the target is correctly chosen. The challenge now is we've got to find these targets. "

 

Symptoms of leukemia may include abdominal discomfort, bone and joint pains, and fatigue. Some patients are diagnosed when a routine blood test reveals a high white blood cell count with increased numbers of immature white blood cells.

 

Today's approval of Gleevec for treating the three phases of CML was based on three separate single arm studies in about 1,000 patients. These clinical trials were not designed to determine whether Gleevec improves survival. The sponsor is currently accruing patients for follow-up studies necessary to confirm clinical effectiveness of Gleevec.

 

5/14/01

 

Source

US Food and Drug Administration (FDA).

[Guest guest]

My patient has GIST. gleevac, at this moment, looks to be the future of cancer treatments. He is having no side effects. (!).Cara

 

Hi Cara, Check this out.

 

Emmanuel Segmen

 

 

 

 

 

Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.

 

J Biol Chem 2001 Oct 12;276(41):37747-53 (ISSN: 0021-9258)

 

Boren J; Cascante M; Marin S; Comin-Anduix B; Centelles JJ; Lim S; Bassilian S; Ahmed S; Lee WN; Boros LG Department of Biochemistry and Molecular Biology, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Marti i Franques 1, Barcelona 08028, Spain.

 

Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.

[Guest guest]

thank you Emmanuel:

my question remains: what should be thinking about if I want to prescribe herbs ( I mean besides responding to signs and symptoms). For instance, we know that some chemotherapeutics are cardiotoxic- we know that there are herbs to mitigate these effects.

what, if anything, do I need to be aware of with Gleevec.

 

Cara

Emmanuel Segmen

 

Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.

J Biol Chem 2001 Oct 12;276(41):37747-53 (ISSN: 0021-9258)

Boren J; Cascante M; Marin S; Comin-Anduix B; Centelles JJ; Lim S; Bassilian S; Ahmed S; Lee WN; Boros LG

Department of Biochemistry and Molecular Biology, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Marti i Franques 1, Barcelona 08028, Spain.

Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.

 

 

[Guest guest]

" Gleevac "

 

Who comes up with these drug names? Some of the ugliest words.

 

But there must be a rhyme and reason to it- lots of them end with

consonants.

 

Just my own musing...

 

B

 

 

 

Brian Benjamin Carter, M.Sci., L.Ac.

http://www.pulsemed.org/briancarterbio.htm

Acupuncturist & Herbalist

Editor, The Pulse of Oriental Medicine

Columnist, Acupuncture Today

(619) 208-1432 San Diego

(866) 206-9069 x 5284 Tollfree Voicemail

 

The PULSE of Oriental Medicine

http://www.pulsemed.org/

The General Public's Guide to Chinese

Medicine since 1999... 9 Experts,

240+ Articles, 195,000+ readers....

 

Our free e-zine BEING WELL keeps you

up to date Sign up NOW. Send a blank email to:

beingwellnewsletter-

 

[Guest guest]

" Gleevac " , though disgusting sounding to me as well, reminds me of something

" vaccuuming " gunky gooey stuff out of my system...gleefully removing the

diseased parts.

 

Julie

 

 

> " Gleevac "

>

> Who comes up with these drug names? Some of the ugliest words.

>

> But there must be a rhyme and reason to it- lots of them end with

> consonants.

 

>

> Just my own musing...

>

> B

[Guest guest]

I think Gleevec was one of the Sleestak's kids.. but some of the movie

companies were suing Novartis for the rights to use Sleestak and lost

out, so the kid is going to cash in on the $5 royalty for each pill

sold. Ahh... if I could just remember TCM like I remember old corny

sci-fi shows..

Geoff

 

> __________

>

> Message: 11

> Wed, 25 Jun 2003 23:49:05 -0700

> " Brian Carter " <bbcarter

> Re: Gleevac

>

> " Gleevac "

>

> Who comes up with these drug names? Some of the ugliest words.

>

> But there must be a rhyme and reason to it- lots of them end with

> consonants.

>

> Just my own musing...

>

> B

[Guest guest]

Hi Cara,

 

Based on the paper below, you might note that Gleevec is typical of a class of chemotheraputic agents that are protein kinase inhibitors. They unhinge the connection between reading a gene and the subsequent polypeptide production. Great for stopping a malignancy ... not great for the overall function of the body. So you will have to give support for general debilitation, weakness, fatigue and so on.

 

A special side-effect of Gleevec is Severe periorbital edema secondary to STI571 (Gleevec). You can look up this paper title in Medline or other search engine if you want to read the paper, or ask me and I'll send you an abstract. Apparently some people taking Gleevec need surgical intervention for edema that forms inside the orbit of the eye and may cause visual obstruction. You can think about what that means in Chinese medicine. Since normal kidney activity represents 25% of a resting basal metabolic rate, you can probably get a clue as to what Gleevec does to kidney function if periorbital edema is a major side-effect. My guess is that the kidney pulse of your patient will have a special story to tell you.

 

Emmanuel Segmen

 

 

-

Cara Frank

Wednesday, June 25, 2003 6:19 PM

Re: Gleevac

 

thank you Emmanuel: my question remains: what should be thinking about if I want to prescribe herbs ( I mean besides responding to signs and symptoms). For instance, we know that some chemotherapeutics are cardiotoxic- we know that there are herbs to mitigate these effects. what, if anything, do I need to be aware of with Gleevec. CaraEmmanuel SegmenGleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem 2001 Oct 12;276(41):37747-53 (ISSN: 0021-9258) Boren J; Cascante M; Marin S; Comin-Anduix B; Centelles JJ; Lim S; Bassilian S; Ahmed S; Lee WN; Boros LG Department of Biochemistry and Molecular Biology, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Marti i Franques 1, Barcelona 08028, Spain. Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.