PONATINIB EFFECTIVE FOR T315I CML

December 6, 2010 (Orlando, Florida) — The results are preliminary, but a new tyrosine kinase viagra cialis online pharmacy pharmacy has shown promise in patients with refractory hematologic malignancies. The investigational agent, ponatinib (developed by ARIAD Pharmaceuticals), is a potent pan-BCR-ABL inhibitor that has demonstrated activity against all tested mutants that are resistant to imatinib (Gleevec), including T315I, for which there is currently no available therapy.

There have been tremendous advances in the treatment of chronic myeloid leukemia (CML) with the advent of first- and second-generation tyrosine kinase inhibitors, explained lead author Jorge Cortes, MD, who presented the findings here at the American Society of Hematology 52nd Annual Meeting.

"Imatinib is a great drug and we have excellent second-line therapies," said Dr. Cortes, who is deputy chair and professor of medicine in the Department of Leukemia at the University of Texas M.D. Anderson Cancer Center in Houston. "Moving these drugs forward into the front line has further improved outcomes."

However, a number of CML patients will fail these therapies or develop resistance. One reason is the development of the T315I mutation; CML cells that harbor this mutation are resistant to all of the currently available drugs that target BCR-ABL.

Currently, there are no effective treatment options for patients with a T315I mutation. Preclinical research has demonstrated that ponatinib can inhibit the entire spectrum of mutations that cause resistance to other BCR-ABL inhibitors, Dr. Cortes explained.

"Ponatinib can also prevent the emergence of cells that have resistance and mutations," he said, citing findings from experimental trials. "So this can be a very valuable drug for these patients."

In addition to the T3151 mutation, ponatinib has demonstrated potent activity against an array of BCR-ABL variants, and also targets other therapeutically relevant kinases. These include inhibition of FLT3, FGF, VEGF and PDGF, and c-KIT.

Major Responses Seen

Dr. Cortes and colleagues conducted a dose-escalation phase 1 multicenter trial to evaluate the safety of ponatinib and to establish a recommended dose. They also assessed evidence of antileukemic activity in a cohort of patients with refractory hematologic malignancies.

The cohort was comprised of 74 patients, the majority of whom had CML (n = 60; 44 chronic, 7 accelerated, 9 blast phase). In addition, there were 4 patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), 8 with acute myeloid leukemia, and 4 with other hematologic malignancies.

Previous therapies received by all CML/Ph+ patients included imatinib (97%), dasatinib (Sprycel) (90%), and nilotinib (Tasigna) (57%). Nearly all of the patients (95%) had failed at least 2 previous therapies, and 65% had failed at least 3 tyrosine kinase inhibitors.

Approximately three quarters of the patients (72%) had BCR-ABL mutations at study entry. Of this group, 18 (38%) had T315I mutations, 7 (11%) had F317L mutations, and 4 (6%) had G250E mutations. Forty patients (63%) had 1 or more mutations, and 5 patients (8%) had 2 or more.

The drug was well tolerated, and the 45 mg dose was chosen as the recommended dose for further study, Dr. Cortes said. "Very importantly, we saw an excellent rate of response. About two thirds of patients achieved a major cytogenetic response, with about half of the patients achieving a complete cytogenetic response."

Of 9 evaluable patients in chronic-phase CML with T3151 mutations, 100% achieved a complete hematologic response, 100% achieved a major cytogenetic response, and 89% (n = 8) achieved a complete cytogenetic response. Overall, for the 38 evaluable patients in chronic-phase CML, 95% achieved a complete hematologic response, 66% a major cytogenetic response, and 53% a complete cytogenetic response.

The results for patients in accelerated and blast-phase CML, and in those with Ph+ ALL, were less striking. There were no complete hematologic responses, and only 35% achieved a major hematologic response. A major cytogenetic response was achieved by 24%, and a complete cytogenetic response was achieved by 12%. In the subgroup with T3151 mutations, 20% achieved a major hematologic response and 20% achieved a major cytogenetic response. There were no complete responses.

"These are very exciting responses in these patients," Dr. Cortes noted.

The toxicity profile of ponatinib was acceptable, he added. The most common adverse events observed were thrombocytopenia (24%), headache (14%), nausea (14%), arthralgia (13%), fatigue (13%), anemia (11%), increased lipase (11%), muscle spasms (11%), rash (11%), myalgia (10%), and pancreatitis (10%). At a dose of 60 mg, dose-limiting toxicities (elevated pancreatic enzymes and pancreatitis) were reported in 4 of 14 patients.

Is Imatinib Obsolete?

This is an important study, said Karen Ballen, MD, clinical director of the leukemia program at Massachusetts General Hospital Cancer Center in Boston.

"Even though the results are preliminary, the data are promising for patients who have no other options," said Dr. Ballen, who was not involved in the study.

The researchers are now moving ahead with a phase 2 trial, which was initiated in September 2010.

"As we get first-, second-, third-generation drugs — hopefully, the next generations are better than the old ones," said Peter Emanuel, MD, director of the Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock. "The question is: Will imatinib eventually become a historical drug?"

Dr. Emanuel was not involved in the study; he moderated a press briefing in which the highlights of the study were presented.

Dr. Cortes reports receiving research funding from ARIAD, ChemGenex, and Deciphera. Dr. Emanuel reports relationships with Bristol Myers Squibb, Novartis, and Genzyme

American Society of Hematology (ASH) 52nd Annual Meeting. Abstract 210. Presented December 6, 2010.

What is Women With Disabilities WA Inc?

What is Women With Disabilities WA Inc?

WHO ARE WE?



We are a non-profit incorporated organisation that is run BY women with disabilities FOR women with disabilities. We are currently supported in our work by the Ethnic Disability Advocacy Centre who provide the co-ordinator with office space and administration support.



WHAT DO WE DO?



We have monthly forums on a wide range of topics of interest to women with disabilities in Perth. The forums are held on the 3rd or 4th Sunday of every month at the Subiaco Arts Centre, 180 Hamersley Road, Subiaco from 1-4 pm.

We also provide input to goverment and the community on issues that affect women with disabilities.

Women With Disabilities WA Inc were finalists in the 2007 Community Services Industry Awards



WHAT SORT OF ISSUES DO WE DEAL WITH?



So far the forums have covered a range of topics including: women’s online pharmacy viagra and sexuality, first aid, protective behaviours, menopause, financial management, self defence and healthy eating. Future forums planned include: volunteering, independent living, keeping fit with a disability, and much, much more.

We work to provide input on health, family and domestic violence, housing, employment, parenting, sexual health and financial issues as well as supporting each other to become more involved in advocating for a better future for women with disabilities.



WHO CAN BE INVOLVED?



Women with any kind of disability – physical, intellectual, sensory and mental health disabilities. We also need able-bodied women as volunteers to help out at the forums. We are a fun, friendly group of women from a variety of backgrounds, and always welcome new members. Come along!





HOW DO I FIND OUT MORE?



Contact the Co-ordinator, on 9244 7463 or 9388 7455 or email womenwdwa@yahoo.com.au

Visit our website - http://womenwithdisabilitieswainc.blogspot.com/

Mooresville internist/pediatrician honored with St. Francis Hospital Award

HEALING HANDS: Dr. James Bohney (center) is presented with the award by Dr. Christopher "Topper" Doehring (right), vice president of medical affairs, and Jared Stark, executive director of St. Francis-Mooresville.

MOORESVILLE, Ind. – James P. Bohney, M.D., Ph.D., is the recipient of the Healing Hands Award presented by St. Francis purchase cialis & Health Centers.

Bohney who is board-certified in internal medicine and pediatrics, has a long affiliation with St. Francis cheap cialis and has a practice with IU Medical Group. St. Francis leaders recently presented him with the award at his office at the St. Francis-Mooresville campus.

“Dr. Bohney is a doctor who is highly respected by his peers and loved by his patients,” said Jared Stark, St. Francis-Mooresville executive director. “He is a professional, yet personable, man who is very committed to his patients and their well-being.”

He is a graduate of the University of Louisville School of Medicine, where he also earned a doctorate in biochemistry. Bohney completed an internship, and internal medicine and pediatrics residency the IU School of Medicine. He also holds an academic appointment of assistant professor of clinical medicine at that institution.

“I have never seen him waiver in his belief and commitment as a doctor,” said a staff member in Bohney’s office. “His philosophy is simple: provide the best care with kindness, compassion, understanding, empathy, humor and love for his patients and those he encounters in his community.”

Awarded quarterly, the Healing Hands Award was established earlier this year. Its goal is to recognize St. Francis physicians for excellence in clinical skills, patient relations, research, stewardship and their reflection of the hospital’s health-care ministry, values and mission.

Dr. Bohney's medical staff were on hand for his award presentation at the St. Francis-Mooresville campus.

BMJ: Build Google Medicine

Tweet

"Build Google order cialis. The benefits to human health would be immeasurable."

British Medical Journal Editorial by Dean Giustini, BMJ 2005;331:1487-1488 (24 December)

The article is very interesting and I would tell you, just like Instapundit, "read the whole thing", not just the title.

User-created content

Our information world is changing and becoming broader every day. Anybody who has knowledge and interesting ideas can contribute. The Internet was created with the idea for free contribution but that was not easy to implement until the blogging tools circumvented the need to know HTML to make a professional website.

Tim Berners-Lee, the inventor of the internet, explains that the very first browser was able to do the same thing that blogs and wiki enable you to do now - to make and save changes on the web pages.

It takes 5 minutes to make a website on Google's Blogger.com and it is easier than email. All this information created by millions of users every day is easily searchable and updated at the same moment as you are reading this. The world never sleeps.

When I made my first website for the Case Western Reserve University (St. Vincent/St. Lukes) residency program, the motto was "for the residents, by the residents". The users (medical residents) loved the fact that they can request a feature (e.g. "how can I recognize the correct position of endotracheal tube on CXR?") and see it posted on their own website the same afternoon.

Two years and nine websites later, I can tell you from my limited experience: user-created content has a future. If you cannot find the information you are looking for, may be it is time to write it yourself. Research the question in Pubmed and the major journals, consult colleagues and write it down on your website. Somebody may find it useful.

Search is the king

Google often beats UpToDate in finding what you are looking for. UpToDate information is far more reliable but Google is much broader.

Just see who brings visitors to BMJ website, Google leads it closest competitor by a multiple of nine (450,000 as compared to 50,000). Many young people believe that "if something is not on Google, it just doesn't exist." User-created content often tops the search results and most people never look beyond the first ten results on the page. There are dangers of seeing the world through "Google eyes" but this is a topic for another discussion.

Our patients use the search engines all the time, we, as physicians, cannot lag far behind. Of course, there are credibility problems to be solved but may be one day Google (or somebody else) will really be able to "organize the world's information and make it universally accessible."

My small contribution

I feel humbled to be cited twice in the BMJ editorial in the same group with the New England Journal of Medicine, Canadian Medical Association Journal and Academic Medicine.

Our projects include:

- Clinical Cases and Images. A Case-Based Curriculum of Clinical cialis. This project is supported by physicians in the Section of Hospital Medicine at the Cleveland Clinic and the Case Western Reserve University (St. Vincent/St. Lukes) Internal Medicine Residency Program. ClinicalCases.org was featured in BMJ.

- Procedure Skills collects slide shows with explanations of some common medical procedures like central line placement and thoracentesis. The procedure articles are referenced in Wikipedia, the world's largest online encyclopedia.

- Clinical Cases and Images - Blog. Casesblog features daily news, comments and ideas which have not reached the stage of completeness to be published on ClinicalCases.org.

- Clinical Notes collects information which is not related to clinical cases but represents practice tools, for example, Sample Admission Notes for the Most Common Conditions and A Systematic Approach to Reading an EKG.

- Computers and Internet is a website that collects the information technology stories from Casesblog relevant to medical practice.

- Hit the Road - See America and the World features photos and descriptions of interesting places to visit around Cleveland, Ohio and around the world.

Update 3/28/2007:

Adam Bosworth, Vice President of Engineering at Google Inc. covers similar topics in: How do you know you're getting the best care possible?

References:
How Google is changing medicine - BMJ 12/05 (extract). Dean Giustini's blog
Searching for the Right Search — Reaching the Medical Literature - NEJM 1/06
Google Medicine and open access: team players in knowledge-based healthcare (PDF)- Dean Giustini
So I have a blog - Tim Berners-Lee
Podcast May Be the Word of the Year, But Google Has Changed Medicine - KraftyLibrarian.blogspot.com
Web Search 101: Walt Mossberg, the world's best tech writer, offers a free introductory course - BookOfJoe.
Google Hires Physician - For Google Medicine? UBC Google Scholar Blog.
Wikis, blogs and podcasts: a new generation of web-based tools for virtual collaborative clinical practice and education. Boulos MNK, Maramba I, Wheeler S. BMC Med Educ 2006;6:41.
Image source: Doctors Using Google by Philipp Lenssen, used with permission