Cancer #1 Killer

gdpawel · Posted: Sat Jan 15, 2005 8:38 pm Post subject: Cancer #1 Killer

The Associated Press reported that Cancer is the Top Killer for Those Under 85. There has been no real progress in the treatment of most common forms of cancer. Recent NCI data showed that U.S. cancer mortality rates have increased and age-adjusted cancer mortality rates in response to treatment have not improved in several decades, despite the introduction of many new drugs. There is a mind-set of cancer culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else. Tumor shrinkage should not be the criteria for approving cancer drugs.

The January 10, 2002 issue of the New England Journal of Medicine noted that 20 years of clinical trials yielded survival improvement of only 2 months for patients with advanced lung cancer. It also pointed out that oncologists at a single institution may obtain a 40-50% response rate (not cure) in a tightly controlled study, but when these same studies are administered in a real world setting, the response rates (not cure rates) decline to only 17-27%.

In the March 15, 2004 issue of the Journal of Clinical Oncology, an editorial stated that a review of all the large, prospective, randomized trials published comparing the newer taxane-based regimens, none of these regimens have increased either complete response rates or overall survival, with median survivals remaining at two years or less. This is precisely the same results which were being obtained 30 years ago.

The results of nearly 30 years of clinical investigation in the treatment of patients with cancer, neither standard or high-dose regimens had done a great deal to improve the outcome of patients. For over the past 20 years, they relentlessly combined chemical agents in various regimens with ever-increasing dose intensity and the survival for patients is exactly the same, less than two years. Not a hint of significantly improved survival.

In the March 22, 2004 issue of Fortune, an extensive expose of why there has been no progress in drug treatment of cancer in three decades, the author writes that it is not localized tumors that kill people with cancer, it is the process of metastasis, 90% of the time. Aggressive cells spreading to the bones, liver, lungs, brain or other vital areas, that are wreaking havoc. You'd think cancer researchers would be bearing down on the intricate mechanisms of invasion and spread? However, according to a Fortune examination of NCI grants going back to 1972, less than 0.5% of study proposals focused primarily on metastasis, trying to understand its role in cancer or just the process itself. Of nearly 8,900 NCI grant proposals awarded in 2003, 92% didn't even mention the word metastasis.

So pharmaceutical companies don't concentrate on sloving the problem of metastasis (the thing that really kills people); they focus on devising drugs that shrink tumors (the thing that dosen't). There is a national problem in the way we treat the problem. It is time to set aside empiric "one-size-fits-all" treatment of cancer for "individualized" treatment based on testing the individual properties of each patient's cancer.

Perusing this article, by a cancer survivor himself, will enlighten one as to the accomplishments of cancer medicine over the last thirty years.

http://blog.aperio.com/articles/Fortune_Cancer.pdf

merianne · Regular Joined: 06 Dec 2004 Posts: 16 Location: lakeland

[quote="gdpawel"]There has been no real progress in the treatment of most common forms of cancer. Recent NCI data showed that U.S. cancer mortality rates have increased and age-adjusted cancer mortality rates in response to treatment have not improved in several decades, despite the introduction of many new drugs. There is a mind-set of cancer culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else. Tumor shrinkage should not be the criteria for approving cancer drugs.

The January 10, 2002 issue of the New England Journal of Medicine noted that 20 years of clinical trials yielded survival improvement of only 2 months for patients with advanced lung cancer. It also pointed out that oncologists at a single institution may obtain a 40-50% response rate (not cure) in a tightly controlled study, but when these same studies are administered in a real world setting, the response rates (not cure rates) decline to only 17-27%.

In the March 15, 2004 issue of the Journal of Clinical Oncology, an editorial stated that a review of all the large, prospective, randomized trials published comparing the newer taxane-based regimens, none of these regimens have increased either complete response rates or overall survival, with median survivals remaining at two years or less. This is precisely the same results which were being obtained 30 years ago.

The results of nearly 30 years of clinical investigation in the treatment of patients with cancer, neither standard or high-dose regimens had done a great deal to improve the outcome of patients. For over the past 20 years, they relentlessly combined chemical agents in various regimens with ever-increasing dose intensity and the survival for patients is exactly the same, less than two years. Not a hint of significantly improved survival.

In the March 22, 2004 issue of Fortune, an extensive expose of why there has been no progress in drug treatment of cancer in three decades, the author writes that it is not localized tumors that kill people with cancer, it is the process of metastasis, 90% of the time. Aggressive cells spreading to the bones, liver, lungs, brain or other vital areas, that are wreaking havoc. You'd think cancer researchers would be bearing down on the intricate mechanisms of invasion and spread? However, according to a Fortune examination of NCI grants going back to 1972, less than 0.5% of study proposals focused primarily on metastasis, trying to understand its role in cancer or just the process itself. Of nearly 8,900 NCI grant proposals awarded in 2003, 92% didn't even mention the word metastasis.

So pharmaceutical companies don't concentrate on sloving the problem of metastasis (the thing that really kills people); they focus on devising drugs that shrink tumors (the thing that dosen't). There is a national problem in the way we treat the problem. It is time to set aside empiric "one-size-fits-all" treatment of cancer for "individualized" treatment based on testing the individual properties of each patient's cancer.

Perusing this article, by a cancer survivor himself, will enlighten one as to the accomplishments of cancer medicine over the last thirty years.

http://blog.aperio.com/articles/Fortune_Cancer.pdf[/quote]

I would like to express what is a personal opinion about cancer in relation to this article. My opinion is that most people whose life expectancy declines during cancer, declines due to the slash, drug, burn treatment methods for cancer. When some one gets a cold, we tell them to take vitamin C, stay well hydrated and get extra rest. To build the immune system back. With Cancer, we take the weakened immune system and feed it chemicals, to make it weaker, burn not only cancerous tissue out of the body, but healthy tissue as well, setting up additional chances for infection, and we hinder the body in other self healing ways by surgical invasion, for diagnostic purposes. I don't think that any procedure that leaves the body weaker than it was before, can possibly cure. It makes no sense. It reminds me of the days when we put rubbing alcohol on a wound to protect us from infection. It burned like the dickens and dryed out the skin so badly, it took twice as long for the skin to heal as would have if it had been merely cleaned with running water. Then we were told the pain was being caused by the germs dying!!. I am afraid, that until the medical industry comes up with immune system building techniques that improve the way the body fights disease, we will continue to kill more patients with cancer than are cured.
_________________
If the world ended tomorrow, there would still be today.

gdpawel · Posted: Thu Feb 03, 2005 10:13 pm Post subject: The Immune System

I could not agree with you more. The body's immune system attacks and eliminates not only bacteria and other foreign substances but also cancer cells. A cancer cell is not a foreign cell; rather, it is a cell whose biologic function has been altered in such a way that it doesn't respond to the body's normal mechanisms for controlling cell growth and reproduction. The abnormal cells can continue to grow, resulting in cancer. Much of the body's protection against cancer is carried out directly by cells of the immune system rather than by antibodies circulating in the bloodstream. Cancer is more likely to occur in people who take drugs that suppress the immune system than in people with normal immune systems.

gdpawel

We have produced an entire generation of investigators in clinical oncology who believe that the only valid form of clinical research is to perform well-designed, prospective, randomized trials in which patients are randomized to receive one empiric drug combination versus another empiric drug combination.

What passes for a successful experiment in clinical oncology? Henderson, et al, entered 3,100 breast cancer patients in a prospective, randomized study to compare cyclophosphamide/doxorubicin alone versus cyclophosphamide/doxorubicin plus Taxol (in the adjuvant, pre-metastatic setting). The results were microscopically positive, at best, and cannot begin to justify the enormous financial and human resources expended (while making no effort at all to test and improve methods to individualize treatment).

But these results changed the face of the adjuvant chemotherapy of breast cancer. Cyclophosphamide+Doxorubicin+Taxol became standard of care. Taxol recently went off patent. Now the thrust is to identify on-patent therapy which is microscopically better in clinical trials of one-size-fits-all treatment. Already, the community-based oncologists are migrating to Cyclophosphamide+Doxorubicin+Docetaxel (expensive/remunerative) so what was the purpose of doing that 3,100 patient prospective, randomized Henderson study?

Some academic oncology groups have as their major ovarian cancer project, clinical trials to show that Taxotere (Docetaxel) can now be the new "standard" therapy. Patients are treated with Taxol plus Carboplatin. If (or when) Taxol plus Carboplatin doesn't work, they'll be crossed over to Taxotere, a drug which is mostly (if not completely) cross resistant with Taxol, for which the cancer clinic will collect several thousand dollars per patient from the large pharmaceutical company if and when they are treated with this drug (delaying the patient's treatment and possibly subjecting them to a horrible death).

There were a couple of recent clinical trials, one dealt with breast cancer and the other dealt with lung cancer; both of them had the drug Taxotere (Docetaxel) in their repective studies. These kind of chemotherapy studies have never yielded any kind of meaningful advance. It's being done simply because Taxotere (Docetaxel) is an on-patent drug which has a Big Pharma sponsor willing to spread around a lot of money to identify and expand indications.

We are getting an expanding list of treatments which are partially effective in a minority of patients, ineffective in a majority, remarkably effective in a few, while being enormously expensive. The fastest way to improve things is to match treatment to the patient.

All the rigorous clinical trials identified are the best treatments for the average patient. But cancer is not an average disease. Cancer is far more heterogeneous in response to various individual drugs than are bacterial infections.

The tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing the individual properties of each patient's cancer. There are over 100 different therapeutic drug regimens which any one or in combination can help cancer patients. The system is overloaded with drugs and underloaded with wisdom and expertise for using them.

In clinical trials, many patients are excluded because they could not complete the rather arduous treatment. So randomized comparisons are of healthier treated patients against all the controls, rendering a lot of trials invalid. All the rigorous clinical trials that have been identified are the "best" treatments for the "average" patient. This has been referred to as the lowest common denominator theory of cancer treatment. But cancer is not an "average" disease. Cancer is far more heterogeneous in response to various individual drugs than are bacterial infections. The present system exists to serve the clinical investigators and the clinical oncologists, but not to serve the best interests of the cancer patients.

One of the main problems in providing effective chemotherapy is the situation that every patient is unique. Tumors grow and spread in different ways and their response to treatment depends on these characteristics. The amount of chemotherapy that each patient can tolerate varies considerably from patient to patient. Therapeutic protocols currently in use are limited in their effectiveness because they are based on the results of clinical trials conducted on a general patient population, yet no two patients are alike.

Recent NCI data showed that U.S. cancer mortality rates have increased and age-adjusted cancer mortality rates in response to treatment have not improved in several decades, despite the introduction of many new drugs. There is a mind-set of cancer culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else. Tumor shrinkage should not be the criteria for approving cancer drugs.

A patient responds to therapy when their tumor shrinks, but apparently this has nothing to do with survival. A tumor responds, that is, shrinks a little, then quickly grows and spreads. The cancer comes back with a vengeance and the cancer patient is given a death sentence by his/her oncologist who will wash his hands of it.

Experimenting on cancer patients is permissible behavior for medical oncologists. They have been allowed free access to their bodies with no accountability. After a cancer patient dies, there are no repercussions. The oncologist's compensation, reputation, position, career prospects and opportunities for advancement have no relationship to whether or not his patients live or die.

gdpawel · Posted: Sun Nov 13, 2005 9:46 pm Post subject: The War on Cancer

The needed change in the "war on cancer" will not be on the types of drugs being developed, but on the understanding of the drugs we have. There are already over 100 different therapeutic drug regimens out there, and 400 are in the pipeline. Any one or combination of them can help cancer patients. The system is overloaded with drugs and under loaded with wisdom and expertise for using them.

There are many cancer drug regimens, all of which have approximately the same probability of working. The tumors of different patients have different responses to chemotherapy. Tumors grow and spread in different ways and their response to treatment depends on these unique characteristics. The amount of chemotherapy that each patient can tolerate varies considerably from patient to patient. It requires individualized treatment based on testing the individual properties of each patient's cancer.

Under this approach, scientists study how an individual's cancerous cells respond to drugs. Doctors have learned that even when the disease is the same type, different patients' tumors respond differently to chemotherapeutic drugs. More and more physicians and patients are turning to "individualized therapies" to treat cancers, not just "targeted therapies." Without individualized testing, it's difficult to determine which drugs are best for patients who don't respond to standard therapies.

Herceptin is only for the estimated 20% of breast cancer women at risk for recurrence. However, Gene Expression Assays are panels of markers that can predict the likelihood of cancer recurrence in various populations. By testing the gene expression markers of a patient, oncologists can identify those patients unlikely to benefit from chemotherapy from those that would, saving the other 80% of cancer patients the added expense, suffering and even death from having to take chemotherapy.

What a cancer patient would like ideally, is to know whether they would benefit from adjuvant chemotherapy. If so, which active drugs have the highest probability of working, which Chemotherapy Sensitivity and Resistance Assays can test for drug activity against a tumor, and what drugs are relatively non-toxic in a given patient , which Pharmacogenomic Testing can identify.

Whether a patient would benefit from adjuvant therapy depends on two things: (1) whether the tumor is "destined" to come back in the first place and (2) whether the tumor is sensitive to drugs which might be used to keep it from coming back.

The gene expression markers (assays) actually can be calibrated to provide information both about the possibility of recurrence and also chemosensitivity. The problem is dissecting one from the other. Studies to date have just looked at whether people had a recurrence.

You can identify gene expression patterns (via assays) which correlate with this. But it can be hard and even impossible to tell what exactly you are measuring: is it intrinsic aggressiveness of the tumor? sensitivity to adriamycin? sensitivity to cyclophosphamide? sensitivity to taxol? sensitivity to tamoxifen? You find a gene expression panel which correlates with something, but picking apart the pieces is hard.

You can begin to do this if you combine gene expression studies with cell culture studies. Use the cell culture as the gold standard to define the difference between sensitivity and resistance. Then see which pattern correlates with which for individual tumors and individual drugs. It can theoretically be done (and certainly will be done, over time), but it's not easy.

And then you come to the 1,000 pound gorilla of a question: What effect will the different individual drugs have in combination in different, individual tumors? This is where cell culture assays will always be able to provide uniquely valuable information. But it's not one versus the other. The best thing is to combine these different tests in ways which make the most sense. One month's worth of herceptin + avastin costs $8000. That's without any docetaxel and blood cell growth factors and anti-emetics. If nothing else, we can't afford too much trial and error treatment.

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