ETHICAL ISSUES IN CANCER THERAPY USED IN CLINICAL TRIALS.
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In desperate times and in situations where there is no known standard therapy left or existing, patients are involved in various phases of clinical trials and off label use of medications occurs.  One difference between off label use with On label use is that early on, people had been willing to put their life at risk, and consented to participate in a clinical trial aimed at proving a point or concept.. These trials often are with a limited scope of objectives to reduce specific biases. But once proof of concept is established, can we extrapolate  these findings to other parallel situations?  Or do we need to do clinical trials even though similar situations, concepts, mechanisms and possible responses apply?  Several scenarios can be asked:

1. If A leads to B and B leads to C, can we conclude without a trial that A leads to C?
2. If A=B and B=C, can we conclude that A=C ?
3. If A-B=C can we conclude the A-C=B?
4. If A using B gets C, therefore A using C gets B?

While some of the scenarios are clearly true, some are not fully true and some conclusions are completely wrong. And resulting consequences could be devastating. The variables are what happens between the letters. And the intensity of the quality of the conclusion depends very much on these various variables.  Ethicists around the world struggle with these Issues all the time.

When it comes to Humans, the variables become endless: Gene differences, gender, age, previous exposures, set of circumstances, state of main organs, and susceptibilities are just a few known and unknown variables.   Reaction to something known will depend on the mentioned variable.  And even though the drug and side effects are known, these variables still question or challenge us because they can change the outcome.  The safety or acceptability of the outcome determines or influences the ethical nature of the outcome.  The moral nature of the outcome is another dimension that is part of the Ethical decision and is a tall order that also nees do be met.
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Case in point:

3 decades ago a young researcher was working with a drug that was banned because pregnant women who took the drug had babies with short limbs. The drug was Thalidomide of course.  He was trying to know why this drug led to this calamity.  History taught us that restricted growth of blood vessels in the embryo was one of the main reasons; of course we know now.  But as he worked with Thalidomide, he fell ill.  He was diagnosed with Myeloma.  He wanted to learn more about his disease and soon learned about the pathways in Myeloma and quickly concluded that based on what he knew about Thalidomide, it could help in Myeloma.  He also knew that it would take time for the drug manufacturer to allow the use of the drug for his condition.  Off label use was authorized by someone in this desperate situation and the rest is history!
Now that we know the drug used is effective, was it ethical to try or allow the use of thalidomide without having the results of a clinical trial?  This situation judged today brings out the notion that what is not ethical today may not be unethical tomorrow. The ethical nature of a practice is relative to time, place and culture and? you think it, it's good!

Case in point 2:

Dr Maurie Markman commented on a case about the possible use of Bexarotene, a medication approved for treatment of Cutaneous T-cell lymphoma, in Alzheimer dementia.  Based on what target and mechanisms, one may conclude it can work in this disease.  But a physician says "NO" to recommending it off label.
Who should decide, the desperate, but informed patient, or the Doctor?
And what are the possible reasons this Doctor makes that decision?
At what threshold is a trial needed to allow us to conclude that the OFF-LABEL USE IS WORTH WHILE? IS OUR IGNORANCE ENOUGH OF A REASON TO NOT TRY SOMETHING CONSENTED? IS AN ETHIC PANEL ENOUGH PROOF TO ALLOW SUCH A USE?
Or both patient consent and an ethical panel decision need to reach the threshold together?
YOU TELL ME!
SHOULD WE LEARN SOMETHING FROM THE FIRST CASE? 

FDA APPROVED THE GENERIC DOXIL IN REPONSE TO SHORTAGE AND ITS CONSEQUENCES ON ONCOLOGY PRACTICES ACROSS THE UNITED STATES.
The Generic version is manufactured by SUN PHARMA GLOBAL FZE.
Shortage was first believed to be a commercial ploy to increase the price until it became real.   This approval will limit chances of new shortage and will help patients with Myeloma, Kaposi sarcoma and Ovarian Cancers who need this medication the most.

Managing the loopholes in the cell cycle

Cure to cancer is within reach and is within the management of LOOPHOLES. Cancer cells have within their pathways, redundancy that protects these pathways to maintain life of the malignant cell. You close one door, just to see another one open up to ensure that the life of the cancer cell is maintained. So, unless you hit a critical pathway with no escape routes, the treatment result will be partial and temporary. To succeed we need to hit several targets in total and and sometimes sequentially to impose on the cell to choose the path to its natural death (apoptosis). So most treatments which are limited to one or only a few targets prove partially and temporary effective. This is why building an electronic Cell and being able to put in all the pathways and observe where they lead to, what doors open and which ones are closed or closing, which are critical and which lead to apoptosis (natural cell death) is crucial. Which sequence of shut down leads to sure cell death? Right now we are at the step where we are learning about shutting or opening one door and evaluating the sequence of events that follow. But with our model in hand, we can be more comprehensive in our approach. The model will help determine effects on cancer cells by shutting several doors at once, "closing Loopholes" as Tax people would love to say. This approach with target therapy has led to breaking resistance to certain types of cancers that were notoriously resistant. Today, we are starting to have response rates in Melanoma. We have double or triple longevity in Chronic Myeloid Leukemia, GIST, Myeloma etc...Just wait to see what we will get once we manage to give Multistage Multitarget Therapies (MMT). Cure is within the management of Loopholes!