The future of Combidex in question

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John T
Veteran Member


Date Joined Nov 2008
Total Posts : 4269
   Posted 3/23/2010 10:29 PM (GMT -6)   
The attached letter from Dr Barentsz indicates that the future of the Combidex scan is in jepordy. This has been a very useful tool for PC patients that I can personnallly attest to. If something is not done we will lose this valuable tool.

e-mail: j.barentsz@rad.umcn.nl I CV: http://myprofile.cos.com/jbarentsz

 

wapen4 25% 

 

 

Dear Mr. .,

How are you? I am writing this letter to you to ask for your involvement to ensure that a major advance in the evaluation of men with PC (prostate cancer) is not lost.  I am speaking about Combidex, which is also known as Sinerem in Europe.  Combidex is the iron nanoparticle that is used as a contrast agent when combined with MRI (magnetic resonance imaging).  You may hear or read about this as Combidex, Sinerem, or Ferumoxtran-10.  The early papers on this agent also referred to it as USPIO (ultrasmall superparamagnetic iron oxide).  So simply put, Combidex is the iron nanoparticle that enhances the ability of MRI to detect spread of PC to the lymph node.  Unlike CT scans of the abdomen and pelvis which have a sensitivity of about 47%, Combidex has a sensitivity of 92% (only 8% false negatives) compared to 53% false negative reporting with CT.  How can we afford to lose this important advance that is used to determine the patient’s status and thus his treatment?

Some facts:

In March 2005 the FDA decided not to approve Combidex as a lymph node contrast agent. AMAG pharma (at that time Advanced Magnetics) then decided to stop further approval efforts, and to wait to see how successful Guerbet would be in Europe with their approval trial. AMAG pharma was the only producer of Combidex, and gave Guerbet the license for Combidex in Europe. The contrast was shipped to Guerbet, who then distributed the agent in Europe as Sinerem.

A few year ago AMAG decided to stop the production of Combidex. Guerbet had hoped that their appeal to the EMEA (European FDA) would be positive, so that they could start the production of this agent in Europe based on commercial income. However, in December 2007 the EMEA stated that a main study to evaluate the benefit-risk profile of the medicine had failed to statistically demonstrate the efficacy of Sinerem in the central reading. An appeal of Guerbet to re-evaluate the data was rejected recently. As a consequence Guerbet decided in December 2009 , based purely on financial reasons, not to continue efforts in Sinerem.

This means that no Combidex/Sinerem is produced anymore, and that further efforts for approval are cancelled. On April 1 of 2010, the last available batch of Combidex/Sinerem expires. That means that despite approval by the Dutch authorities, as of April 1st I will not be able to perform Combidex MR exams anymore.

What’s new?

Recently AMAG pharma developed a new USPIO agent “ferumoxytol”, which is FDA approved for therapeutic  use in patients with severe anemia, but NOT APPROVED for diagnostic use. It is possible that ferumoxytol may have lymph node enhancing properties similar to Sinerem (Combidex).  However, there have been no published studies to clarify the optimal dose and time interval of MR imaging after injection of this agent, nor has the accuracy in detecting lymph node metastases been determined.  Certainly these studies are mandatory before this agent is considered for widespread use in nodal staging. However, these studies will require a substantial amount of time if  they are to be performed properly: the doses and the optimal imaging window need to be assessed, and the results using surgical dissection and follow-up validated. In my estimation, this will require at least a minimum of two to three years. A comparative study between ferumoxytol and Combidex, which I am willing to coordinate and perform, may speed up this process.

In the time that it will take for ferumoxytol to be evaluated and validated for patients with prostate cancer, it is necessary that men with PC have access to refined nodal staging with Combidex. This opinion is supported by your most prestigious treating physicians involved in PC evaluation & management, as well as their professional organizations in the USA and Europe. Although it is not a desirable situation, I could help having this test made  available in the Netherlands, but resorting to this last resource makes me highly uncomfortable. Therefore, I am in discussion with Dr. Pereira, CEO of AMAG pharma, to help me solve this undesirable situation.

Solution:

The CEO of the Dutch authorities, the Dutch EMEA representatives, and  the  Department of Pharmacology at Radboud University Nijmegen Medical Center  advised me to ask AMAG pharma for permission to use the preclinical, toxicology and safety data and documents of Sinerem/Combidex to apply for non-commercial production of this agent. After obtaining this approval, I can produce Combidex within one year.  As the safety, toxicology and pre-clinical date are excellent, our Ethical Committee and the Dutch authorities allow me to use this agent on patients on a scientific basis. This also may open the way to start combined scientific trials with US and European participants, not only in prostate but also in other cancer types. Therefore, the use of Combidex will be more widespread.

In addition, trials need to be initiated to explore and validate ferumoxytol for use as a nodal contrast agent, which will lead to FDA approval. Together with some of my expert US partners I am willing to help design coordinate and perform these trials.

I firmly believe that continuing with Combidex will not only allow patients to have recourse to a superior staging examination to determine lymph node involvement, but will additionally allow on-going data acquisition to facilitate evaluation of the new agent ferumoxytol.

What do I need from you?

Your help is very important. You are part of a powerful network. Many of you, and your friends and/or family may be able to help by putting political, economical, PR, and moral pressure on AMAG pharma. Please see how you can mobilize your network and focus on our goal to get the license from AMAG pharma.  I would like to form a Combidex Patient Group (CPG), who working together with me and with your referring physicians will coordinate and optimize your “patient  power”. At short term representatives from this group: treating physicians, patients, leaders from patient advocacy groups, leading politicians, leaders of industry, representatives from NIH/NCI, etc need to show Dr. Peirera the importance for patients of the continuation of Combidex.

·      Can you please send me an e-mail telling me, in what way you can help my goal in having Combidex/Sinerem available within the next year?

In addition, I need funds to get the license from AMAG, to produce  Combidex/Sinerem on a non -commercials basis, and to perform international scientific trials. My estimate is $2,000,000 in total. Although I cannot guarantee this right now, I expect that this investment will be paid back through by the MR exams, and by the international trial participants. Can you please indicate if you are willing to give financial support, and if so in what way you like to contribute?

To enhance the importance of the patients’ perspective and demonstrate this to Mr. Pereira, I ask  you to tell me in a few lines how Combidex changed your treatment, and what it meant to you and your family & friends. Please send this letter in an e-mail as a Word file attached, before April 19, as I will have a meeting with Dr. Pereira and his AMAG-team on April 22nd.

·      Can you please send me such a letter before April 19th?

Finally, in order to promote lymph node imaging with Combidex, Dr. Roach and I are planning a meeting on Lymph Node Positive Prostate Cancer on 9/26/10 in San Francisco. Patients are also invited and we would like to include a patient panel as part of the program.

I know that together we will help Combidex to survive!

Kind regards,

Jelle Barentsz, MD, PhD.

 


64 years old.

PSA rising for 10 years to 40, free psa 10-15. Had 5 urologists, 12 biopsies and MRIS all neg. Doctors DXed BPH and continue to get biopsies yearly. 13th biopsy positive in 10-08, 2 cores of 25, G6 less than 5%. Scheduled for surgery as recommended by Urological Oncologist.

2nd Opinion from Dr Sholtz, a Prostate Oncologist, said DX wrong, pathology shows indolant cancer, but psa history indicates large cancer or metastasis. Futher tests and Color Doppler confirmed large transition zone tumor that 13 biopsies and MRIS missed. G7, 4+3, approx 16mmX18mm.

Combidex MRI in Holland eliminated lymphnode mets. Casodex and Proscar reduced psa to 0.6 and prostate from 60mm to 32mm. Changed diet, no meat and dairy. All staging tests indicate that tumor is local and non agressive. (PAP, PCA3, MRIS, Color Doppler, Combidex, tumor reaction to diet and Casodex, and tumor location in transition zone). Surgery a poor option because tumor is located next to the urethea and positive margin is very likely; permanent incontenance is also high probability with surgery.

Seed implants on 5-19-09, 3 hours door to door, no pain, minor side affects are frequency and urgency; very controlable with Flowmax and lasted 4 weeks. Daily activities resumed day after implants with no restrictions. Gold markers implanted with seeds to guide IMRT.

25 treatments of IMRT 6 weeks after seed implants. No side affects at all.

PSA at end of treatment 0.02 mostly the result of Casodex. When I stop Casodex next week expect PSA to rise. Next PSA in November. Treatments and side affects have greatly exceeded my expectations. Glad to have this 11 year journey finally conclude.

JohnT


zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 3/24/2010 7:03 AM (GMT -6)   
I looked at the profile on the doc (link) you have, wow this is quite the qualified appearing expert in his line of work. Dr. Strum knows him and about Combidex and mentioned it in his book back in 2004-5 and still gives recommendations to selective patients to consider having Combidex done on sites like P2P(Patient to Patient) for patient advice on selected cases he reviews their histories and treatments for free and online for others to see info. Amazing to see what some folks have gone through or how wild some cases might be.

I think Dr. Strum just mentioned that in the USA for prostate cancer $500 million or was it billion is spent on our scanning methods(ct, bone, prostascint, MRI's etc.), usually wasted on patients that have usually have only lower stats (usually not even necessary) and almost never find mets in that low risk patient groups, in med to high risk groups probably should have these tests and even some of those don't find anything, these are not precise enough tests is the truth of the matter, they cannot detect micro-mets or minute amounts of PCa. Those dollars could be better spent on other patient assessments, care and ways, was his point.

Combidex does find cancers much better than any USA method we have, and costs a fraction of what the others cost here. It is not perfect but is found to be superior and there might even be questions about the particles in the body for longer term (don't know), still is very useful possible tool. It is a choice for patients, whom need all the choices they can get and find.
Youth is wasted on the Young-(W.C. Fields)


Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25394
   Posted 3/24/2010 7:56 AM (GMT -6)   
It would be a major shame to lose any tool with that much value, any way to change the thinking in this process?
Age: 57, 56 dx, PSA: 7/07 5.8, 7/08 12.3, 9/08 14.5, 10/08 16.3
3rd Biopsy: 9/08 - 7/7 Positive, 40-90% Cancer, Gleason 4+3
Open RP: 11/08, Rht nerves saved, 4 days in hospt, on catheters for 63 days, 5th one out 1/09
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos margin
Incontinence:  1 Month     ED:  Non issue at any point post surgery, no problem post SRT
Post Surgery  PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12
Latest: 7/9 met 2 rad. oncl, 7/9 cath #6 - blockage, 8/9 2nd corr surgery, 8/9 cath #7 out 38 days, 9/9 - met 3rd rad. oncl., mapped  9/9, 10/1 - 3rd corr. surgery - SP cath/hard dialation, 10/5 - 11/27 IMRT SRT 39 sess/72 gys ,cath #8 33 days, Cath #9 35 days, 12/7 - Cath #10 43 days, 1/19 - Corr Surgery #4,  Caths #11 and #12  same time, 2/8-Cath #11 out - 21 days, 3/2- Cath #12 out - 41 days, 3/2- Corr Surgery #5, Caths #13 & #14 same time, 3/6 Cath #13 out - 4 days

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