Answer to a call for help

I responded to a blog  from a man dealing with  a difficult cancer .   He expressed hope that an mRNA vaccine could help him.  He was frustrated with the FDA.  So am I . Here is my comment

I am a medical oncologist and hematologist in Seattle. The information you supply certainly justifies your desperation. It is not sufficient for me to supply any practical advice.

 The options available to you are both too numerous and too few.  I agree that the American (and international) systems for therapeutic approvals are so slow and cumbersome that people are denied potentially useful interventions and die waiting for an acceptable statistical confidence interval. The systems (like the FDA) justify this based on the dangerous unknowns that devolve from unjustified approvals. (They are very fond of the fact that thalidomide [which can cause horrible birth defects] was not approved in this country until it was shown effective in multiple myeloma; and by then, the birth defect side effect known, its administration severally restricted [ allowing the drug company, Celgene, to gain enormous, outrageous profits]. The parenthetical comment is important.  It demonstrates the web of interests that are victimizing you and others like you.

 Drug companies have adopted a "your money or your life” pricing policy which makes the typical new oncology  drug cost $1,000.00 Per DAY ( $360,000. per year).  The rules of the FDA (the product of lobbying by drug companies, insurance companies and other .. with a few good intentions...) restrict its mission to "safety and efficacy." Theoretically cost does not enter into its considerations.  But FDA approval has become very defined.  New drugs are approved ONLY in certain combinations (often forcing the use of toxic medicines in addition to the newly approved one) for very specific stages of very specific diseases. Only certain brands of therapies are approved for specific stages of specific diseases, although nearly identical medicines exist. This practice means that there is no competition for price. Use of the medicine for a less advanced stage of the disease can be denied insurance coverage because it is not approved.  It is particularly egregious in the field of checkpoint inhibitor therapy, an immune therapy that allows the immune system to work harder than it ordinarily would by removing some of the checkpoints. [ I presume this type of therapy has been explored with you]

 

 Approvals (now) require prior “lines” of treatment. A number of older (often more toxic) treatments must be administered   before the patient qualifies for the newly approved treatment. All these restrictions serve to  severely limit the range of utilization of these drugs and, at the same time, keep the prices exorbitantly high by eliminating competition. It is worth remembering that Medicare still cannot negotiate the price of these drugs.

 

At the same time, there are subtle and overt advertising campaigns aimed at you and aimed at your doctors  and probably aimed at the approval process to advance certain therapeutic options regardless of their probability of success in your case. I think a degree of skepticism must accompany the hope generated by new therapies like mRNA vaccines. It is hard to get a good handle on the probability of success. But great effort is spent to make the therapy appear appealing and promising.

 

You, and people like you, are in the midst of a battle that is primarily motivated by economic considerations. Hugely successful therapies that are effective in a broad range of cases will be approved rather rapidly, at least for a very limited spectrum of disease. Otherwise, the system fails so miserably it would be abandoned. But anything less than that is going to be subject to a long and arduous process that will restrict its usage and increase its cost.

 

 

 

 

 

Coronavirus: Lost

There was an interval of at least 2 months between the discovery of coronavirus December 2019 and his first appearance in the United States in Washington state.  It was clear in that time  this was a very dangerous, sometimes deadly, extremely disruptive epidemic.  It makes me very angry that so little was done in the interval.

What ever was left of the part of the government that protects it people failed.  I recognize that it has been stripped of its resources.  It also appears that its administration did not function properly.  I do not understand the details of why testing materials took so long to produce, why the original tests were defective, but I would not be surprised if some profit motive drove this problem.

No one took charge.  That includes Anthony Fauci and it is an indictment of the president, his Department of Health, his supporters and even his powerful detractors.

But this is not a time to review the past mistakes.  The crisis is ongoing

The current mistakes need to be dealt with.  It is apparent that the Providence Hospital system's calling for such strict restriction on the use of protective equipment increases the probability for staff to become infected.  If staff is infected, and there is an asymptomatic cohort spreading virus, that virus is spreading to hospitalized patients and to other staff members.  Restrictions in anticipation of worsening epidemic are worsening the epidemic. Protective equipment should be used wisely.  It should be used carefully, it should not be wasted, but it should be used when needed to protect workers, staff, patient's and the population at large

The restrictions on who can be tested have increased the epidemic.  It creates a cohort of people who suspect that they may spread the virus and who cannot find out if they are  infected.  The delay in reporting is a significant hardship.

There is a clear variation in the severity of disease.  It is not clear to me what causes this variation.  It is possible that minor variations in the virus could cause ultimately less severe disease.  The current model of disease involves a large component of damage by the immune system.  The details of the viral sequence and the proteins that it codes may directly interact with the elements of the immune system that are invoked.  There may be a immunizing strain of the coronavirus that is currently in the population.  Such as strain that approaches this dream could be identified by looking at people who have had a mild case was contacts have also had a mild case.  Such an approach is clearly very dangerous.  Not pursuing such an approach may also be an error

Cancer myths

Since the time of Virchow, the first person to sucessfully apply the microscope to human pathology, cancers have been calssified ccording to their "site of origin." Virchow lived in a time when the details of anatomy were being discovered. With the microscope the pathologists ( histologist) could identify patterns of cells that (seemed) characteristic of particular tissues and/or organs. Amazingly, there was often a correlation between the cell patterns and the gross anatomy - collections of cells that looked like they came from the kidney ofen correlated with the identification of a mass in the kidney! It seems true that cancer cells keep some of the characteristics of their origins. This statement has various levels of meaning. The ususal action ascribed to it is that cancers are catagorized, and thus treated, accoding to their established or presumed cell of origin.
However, we have a deepening understanding of cells that goes far beyond their appearance. Identical appearing "lymphocytes" are standardly differentiated by immuno chemical means and the results generates a varation in treatment. The idea of cell of origin is expanded to include the catagorization of tumors, on the basis of immunocytochemical analyses, to theoretical sites of origin.
The implicit meaning of the idea of cells of origin is that tumors retain characterisitice of their origins that inform their behavior and susceptibilities. I think that there is limited truth to this. THis idea has been a way to generate ideas about potential treatments for cancers. THus, fluorouracil, which causes diarrhea, might be a good tretment for lung cancer; DDT, which causes adrenal failure could treat adrenal cancer, etc. This was not a terrible strategy given the paucity of active agents and the generally low expectations.
The tissue of origin might also predict a general resistance to chemothehrapy and/or other therapies. Thus kidney cells that function to excrete poisons are exprected to be resistant to chemotherapy. The same argument pertains to colon cells or bladder cells. The truth value of this agrgument is not clear to me. Myths?
Along comes molecular biology. There are many components to molecular biology. DNA expression in all its twists and turns ( enhancers, splice choices, siRNA, etc), signal transduction, proteasomes, angiogensis, etc.. each is a model for cancer and each contains some value, none is the whole answer and probably not even their overlap constitutes a complete enough answer to apply across all cancers.

The array of expressed genes is probably the closest we currently come to a functional description of the situation in cancer cells. But the technique is not good. It generates a list of genes that are either overexpressed ot underexpressed in cancers. There is an admixture of statistics that are not clearly appropriate, arbitrary cutoff levels that define over or underexpression, ignorance of the interaction among the genes, etc. But even if all of these issues were sorted out, I am not convinced that the answer would be very useful.

The Oncotype is a commercialization of (an early form) of this technology. It is living its oncology life: Initial excitement, statistical significance in a few clinical trials, commercialization, exorbitant prices and profits, flaws emerge, junked.

social networks and disease

iGoogle

Does cancer also follow social networks? An obvious question. Can he data be mined?
The paper used the Framinghham data.
http://www.nih.gov/news/pr/jul2007/nia-25.htm

Curing cancer

What constitutes a cure ?

A cure means that a disease has been eradicated and will not return. The dictionary says"make healthy again "

Is it really possible? It may depend upon the definition.

Where does the cure take place? In time: that means that the disease never returns.
In the mind : that means that normal life resumes . The thought of the disease returns to the baseline worry.


The worst situation: Treatment is toxic and there is no benefit. Treatment makes the situation worse. Death due to treatment.


The best situation: Cure with no toxicity. Spontaneous cure . It happens.


The usual situation: Treatment provides something less than cure. Treatment is toxic. Is it worth it?

1. The oncologist has several dissperate simultaneous goals. These include

1. cure,
2. prolongation of life,
3. improving quality of life,
4. providing hope,
5. providing accurate and realisitic information,
6. psychological support of both the patient and those who care for him and those that care about him.