Lack of Meaningful Clinical Trials

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 with doxorubicin alone versus cyclophosphamide plus doxorubicin with 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 plus Doxorubicin with 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 plus Doxorubicin with 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.

lindatn

Wonderful points you have made, now how to get it into hands that will listen and do something about it. Cancer remains a big business, if a cure were found big business would be hurting. Linda

AuthorUnknown

Thank you so much for your posting. It is very informative. I know practically nothing about breast cancer, eventhough I was just diagnosed with it, but what I keep reading in my research is "individualized treatment" being described a myraid of ways.

hummingbyrd

lindatn said:

Wonderful points you have made, now how to get it into hands that will listen and do something about it. Cancer remains a big business, if a cure were found big business would be hurting. Linda

Good point Linda. I've made the comment that I do not anticipate finding a cure for cancer, but I do certainly think we are at a point in history where we have the capability of turning cancer into a chronic condition.
I must agree with Greg regarding clinical trials and the NIH or trials funded by drug companies. I am pleased to say the ACS stands apart and independent in their research. Fortunately I am going to get to see that first hand in about two weeks. What an honorable opportunity it will be to witness the selection of which grants the ACS research money shall fund. As a stakeholder we are there to evaluate the "relevency" the research project has to cancer. I for one have very strong opinions against repetitious, redundant studies involving chemotherapy. Best I understand it the ACS is also most interested in revolutionary drugs, theories and methods of prevention. Gotta give them credit for allowing "peers" aka suriviors, caregivers, family members to be involved in selection of grant spending. At least we are getting an inside view and do have some input, something the NIH could definately follow suit and duplicate and should follow the lead of the ACS particularly in light of the fact that the NIH is not spending volunteer dollars or private donations or even corporate dollars! NO on the contrary, the NIH is spending OUR MONEY...OUR TAX DOLLARS! AND the mass MAJORITY of those studies are done with chemo, chemo, chemo. Poison, poison, and more poison! It's high time we, as patients do something about this monster beauracracy dumping our money in the same trash bin. It's time for them to open up clinical trials to be more inclusive than exclusionary. If ACS can work towards making this disease a chronic condition I know dang good and well our government should have the same goal. But it's going to take people with cancer or their friends and family to contact the NIH and each one of our Congressmen and demand something be done. The government claims to be waging a war on cancer. Well if it's a war that they want I think it's war that we can give them, because I know after being in the "trenches" for 5 years I definately know where this war is failing and can certainly offer a better strategical attack. First and foremost is to recognize chemo and radiation, poison and burn is barbaric and it's time to join the 21st century of medicine!
Get some trials that actually involve patients that are in a position of having a fighting chance and try some innovative ideas! I don't know about the rest of you, but I don't feel I have the luxury of penny annie trials that take 5-10 years to prove chemo X is 5% more effective than chemo Y and to have done this extensive study in part because chemo X is about to lose it's patent. As I have said, it's fine with me for our economy to use us as a market resource, but it's not fine with me for them to expect us to sit around and be willing to die for said economical gain!
hummingbyrd

gdpawel

AuthorUnknown said:

Thank you so much for your posting. It is very informative. I know practically nothing about breast cancer, eventhough I was just diagnosed with it, but what I keep reading in my research is "individualized treatment" being described a myraid of ways.

Gene Expression assays are panels of markers that can predict the likelihood of cancer recurrence in various populations.

Chemosensitivity testing is a test for drug activity against a tumor.

Pharmacogenomic testing is a test to identify patients who are likely to have the most (or least) toxicity.

By testing the gene expression markers of a patient, oncologists can identify those patients unlikely to benefit from adjuvant chemotherapy from those that would. If the patient needs adjuvant chemotherapy, by testing the patient's tumor cells and testing the patient toxicity tolerance, the oncologist can select drugs that have a higher probability of being effective for an individual patient rather than selecting drugs based on the average responses of many patients in large clinical trials.

What a cancer patient would like ideally, is to know whether they would benefit from adjuvant chemotherapy (something gene expression assays may be good at). If so, which active drugs have the highest probability of working (something chemosensitivity testing is very good at) and are relatively non-toxic in a given patient (something pharmacogenomic testing should be good at).

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.

roxanne53

hummingbyrd said:

Good point Linda. I've made the comment that I do not anticipate finding a cure for cancer, but I do certainly think we are at a point in history where we have the capability of turning cancer into a chronic condition.
I must agree with Greg regarding clinical trials and the NIH or trials funded by drug companies. I am pleased to say the ACS stands apart and independent in their research. Fortunately I am going to get to see that first hand in about two weeks. What an honorable opportunity it will be to witness the selection of which grants the ACS research money shall fund. As a stakeholder we are there to evaluate the "relevency" the research project has to cancer. I for one have very strong opinions against repetitious, redundant studies involving chemotherapy. Best I understand it the ACS is also most interested in revolutionary drugs, theories and methods of prevention. Gotta give them credit for allowing "peers" aka suriviors, caregivers, family members to be involved in selection of grant spending. At least we are getting an inside view and do have some input, something the NIH could definately follow suit and duplicate and should follow the lead of the ACS particularly in light of the fact that the NIH is not spending volunteer dollars or private donations or even corporate dollars! NO on the contrary, the NIH is spending OUR MONEY...OUR TAX DOLLARS! AND the mass MAJORITY of those studies are done with chemo, chemo, chemo. Poison, poison, and more poison! It's high time we, as patients do something about this monster beauracracy dumping our money in the same trash bin. It's time for them to open up clinical trials to be more inclusive than exclusionary. If ACS can work towards making this disease a chronic condition I know dang good and well our government should have the same goal. But it's going to take people with cancer or their friends and family to contact the NIH and each one of our Congressmen and demand something be done. The government claims to be waging a war on cancer. Well if it's a war that they want I think it's war that we can give them, because I know after being in the "trenches" for 5 years I definately know where this war is failing and can certainly offer a better strategical attack. First and foremost is to recognize chemo and radiation, poison and burn is barbaric and it's time to join the 21st century of medicine!
Get some trials that actually involve patients that are in a position of having a fighting chance and try some innovative ideas! I don't know about the rest of you, but I don't feel I have the luxury of penny annie trials that take 5-10 years to prove chemo X is 5% more effective than chemo Y and to have done this extensive study in part because chemo X is about to lose it's patent. As I have said, it's fine with me for our economy to use us as a market resource, but it's not fine with me for them to expect us to sit around and be willing to die for said economical gain!
hummingbyrd

Thank you both, Greg and Hummingbird,

I am very interested in the clinical trials information and the clinical trials themselves.

I greatly appreciate continued updates on this subject. I hope that Hummingbird can keep us up to date as person in the KNOW about your recent post as a ACS grant selector and stakeholder.

Greg to keep us informed of his up to date knowledge and research of clinical trials.

This would be just great!

Thank you
Roxanne