1. I hope this technology will be brought to masses and we at last will find cancer treatment

Posted at 10:18AM on Jul 6th 2006 by Honey

2. Another great post Jacki

I've been encouraged by data from the recent HERA study - a large study of herceptin in women with early breast cancer. It seems to show (so far) that heart damage is much less common that was previously thought. As you say - its all still very early days - but here's hoping that there are no long term effects waiting to be unveiled.

Like all things in life however - there's a trade off isn't there. We all simply need to decide if the price is worth paying - and I couldn't agree more with your comments on that front.

Best wishes

Posted at 10:40AM on Jul 6th 2006 by Gordon

3. It's a cautionary tale. Herceptin combined with standard chemotherapy will have as many as 4% of women who take the regimen develop symptoms of congestive heart failure, compared with less than 1% of women given chemotherapy alone. It's one of those things that benefits a very few patients a whole lot, is neutral in most, and is bad in a few.

Overt congestive heart failure is a very late and serious manifestation of heart muscle damage. For every patient with frank congestive heart failure, there is probably another two, three, four or five patients with heart muscle damage short of congestive heart failure. The sort of heart muscle damage which can cause fatigue and/or shortness of breath with moderate or mild exertion, which otherwise wouldn't occur.

Herceptin has been in use only a few years. We don't know what will happen 10 or 20 years from now in women who didn't need any adjuvant therapy at all, who would have been cured by surgery alone. Only a minority of patients who receive adjuvant therapy benefit from it. Adjuvant therapy is worth it if the women have to suffer only short term, temporary toxicity, and if it even slightly reduces the probability that their cancers will come back. But if it produces permanent toxicity, whether "chemo brain" or "heart muscle damage," that is a whole different order of magnitude in terms of risk.

Monoclonal antibodies like Herceptin are enormous. Very large molecules don't have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drug affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth. This needs further evaluation. I just hope that a prospective, randomized clinical trial is not the way to go about it.

Posted at 1:00PM on Jul 6th 2006 by Gregory D. Pawelski

4. Gregory's comments above are interesting.

Indeed he posted virtually identical remarks on our blog site at http://www.twinkletwinkles.com/2006/06/herceptin-look-out-theyre-at-it-again.html

If you search for Gregory's name on Google you'll see that he has been a forceful, articulate and intelligent advocate for his views for some time now.

His stance and viewpoint certainly gives food for thought - but there's no doubt that he stands fairly firmly in the camp of those who would seriously question whether chemotherapy / herceptin and the likes should be used at all in the adjuvant setting.

I'm not saying that his views are not well thought out - they very obviously are. Nor am I saying that they may not have some validity - they might and research is now turning towards those very questions.

But I would caution those who read the above comments to keep in mind that Gregory has his own agenda to promote.

Hope this helps

Gordon

Posted at 7:22AM on Jul 7th 2006 by Gordon

5. I was a spouse/caregiver to an ovarian cancer patient. I became intensely interested in cancer medicine by virtue of working through, enduring and surviving my wife's illness. I've gotten a street education by virtue of voluminous reading and hundreds of hours of past and ongoing personal communication with noted authorities in the field.

There is seldom a "standard" therapy which has been proven to be superior to any other therapy. When all studies are compared by meta-analysis, there is no difference.

There are so many new drugs coming down the pike that there is simply no way to evaluate them in prospective, randomized clinical trials. Some trials are positive, some are negative, and it's only after ten years or so that have gone by and 10,000 patients or so, have been enrolled in the trials that anyone can draw conclusions. And by then, what had been the "standard" treatment has now changed, because of all the new drugs which have been introduced. And I wouldn't suggest they hold these new drugs hostage to the really unachievable standard of prospective, randomized clinical trials.

The best chance for discovering the right formula is having "all" the drugs available to oncologists, and allow creativity and insight and the "Art of Medicine" enter into the process. A "standard" therapy would not be for everyone, but having a lot of tools (drugs) available and making use of various tests (molecular and cellular) to match treatment to the patient.

I'm not so sure I would describe it as having my own agenda, but being an advocate for a number of cancer subjects. To paraphrase Martin Luther King Jr: "A scientific communication should be judged on the quality of its content and only secondarily, or not at all, on the qualifications of its author."

Posted at 2:27AM on Jul 8th 2006 by Gregory D. Pawelski

6. Thanks again Gregory

I respect your stand point and completely agree that your contribution can and should be judged on its quality. I'm quite certain that you are as well versed in the literature as many oncologists - and better versed than some. Certainly better versed than me!

As you correctly say "some trials are positive, some are negative, and it's only after ten years or so that have gone by and 10,000 patients or so, have been enrolled in the trials that anyone can draw conclusions"

Those of us long in the tooth in medicine know thats always been the case - and not only for cancer drugs or treatments.

But of course - we have to live in the day to day world too. As a doctor I can only do the best I can with the knowledge I have. As the partner of a breast cancer sufferer, Marjory and I can only work as a team to tackle this thing head on - using our intelligence and our instincts (and our reading) to find the path that suits us best.

The last bit is the most important. All of those dealing with cancer should remain involved enough in their care to figure out what "suits them best" and to then stick with that decision and live with its consequences.

No one has the right answers except the cancer sufferer themselves. Doctors and guys like us posting on blogs can provide input - but in the end the individual and their family have to figure it out for themselves.

Marjory and I weighed up all our options - came to a decision and will now run with it. We'll either do well or we won't - but at least we've been involved and in control throughout.

Marjory is drawn more to the views that Jacki expressed in her original post. If heart problems come down the line then let them come. Yeah - we will have to deal with it if and when it happens but at least she will be here to deal with it.

I agree with you - there is a tendency to jump for any new breakthrough and to grab the good news without properly considering the down sides.

Not all women will benefit from herceptin. Some will be harmed. Maybe time will show more harm than benefit. But for now the balancing act has to be achieved and the decisions taken by the individual.
Staying positive is vital. Hope is crucial - even in the bleakest of circumstances. Losing hope is a disaster.

Being as informed as you can be is very important - and your postings are a vital part in helping build the big picture.

Many of those with cancer will find what you write deeply disturbing and painful to read. Some will misinterpret your intent but balance in life is everything. The light seems all the brighter when you've properly looked at the darkness.

I do not intend any criticism of your writing or your views - your input is a vital part of the jigsaw. Keep at it. Keep questioning. Keep shaking the foundations. But bear in mind the pain that your questions cause for those who are already committed to their own path.

Best wishes
Gordon

PS - this is the most sustained discussion that I've seen on this blog. Jacki .. Dalene ... what do a couple of guys need to do to get a gold star around here??

Posted at 7:49AM on Jul 8th 2006 by Gordon

7. Dear Gregory & Gordan -- Thank you both so much for your commentary on my post about Herceptin and the forces that make it promising and questionable at the same time. I love that my liimited input on the topic has created this great discourse that is definitely thought-provoking for me -- and hopefully for others too.

Thank you,
Jacki Donaldson

Posted at 2:21PM on Jul 8th 2006 by Jacki Donaldson

8. My comment about Monoclonal antibodies like Herceptin being enormous, may be a reason targeted "small-molecule" therapies ruled at the annual ASCO meeting of oncologists. The most exciting results shown came from studies of multitargeted tyrosine kinase inhibitors, small molecules that act on multiple receptors in the cancerous cells, like Tykerb and Sutent.

The trend is away from the monoclonals to the small molecules, a trend which a new predictive test (EGFRx) may be able to hasten. The EGFRx (TM) assay will test molecularly-targeted anti-cancer drugs therapies Iressa, Tarceva, Sutent and possibly Nexavar, because of being small molecules.

However, drugs like Avastin (although a monoclonal antibody) can be tested with EGFRx (TM) because the target of Avastin is not the cells themselves, but rather a hormone (VEGF) secreted by the tumor cells. The Avastin complexes with free VEGF and blocks its action. The EGFRx (TM) test can discriminate between the activity of different targeted drugs and identify situations in which it is advantageous to combine the targeted drugs with other types of cancer drugs.

Most patients are treated not with a targeted therapy drug alone but with a combination of chemotherapy drugs and clinical studies should not be generalized to all patients with cancer (each is different). The EGFRx (TM) assay relies upon a technique known as “Whole Cell Profiling” in which living tumour cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs.

A variety of metabolic and apoptotic measurements are then used to determine if a specific drug was successful at killing the patient's cancer cells. The whole cell profiling method assesses the activity of a drug upon combined effect of all cellular processes, using several metabolic (cell metabolism) and morphologic (structure) endpoints.

Not only is this an important predictive test that, it is also a unique tool that can help to identify newer and better drugs, evaluate promising drug combinations, and serve as a "gold standard" correlative model with which to develop new DNA, RNA, and protein-based tests that better predict for drug activity.

Posted at 7:41PM on Jul 18th 2006 by Gregory D. Pawelski

9. I and Ms Yue, my afflicted beloved, would give anything to take such a risk.

In China it is barely possible to get Herceptin and if you can it is beyond reach financially.

HER2 seems to be the smoldering ashes without a glow that only needs a good immunological ill wind to burst explode into flames.

I suffered Officer Candidate, Airborne, and Bomb Disposal Training in the Military. I hoped at the time that putting myself in harm's way would serve some greater good--ya, I really did. Herceptin treatment is no different: Roche has a promising, but imperfect drug. It saves lives while taking some in the process. I would volunteer, if I could, to take the medicine for me and for the greater good that would come of my success or failure. Ms Yue feels the same.

The women here are not briefed on how to reduce the swelling caused by lymphedema and compression bandages, believe it or not, are too costly to just hand out.

It is a battle we would love to fight in.

Best, and good luck from China.

Posted at 11:46AM on Jul 31st 2006 by Lonnie