Chemo sensitivity testing and vaccines

[Bill]

katie- thanks for the suggestion. heres the question -

has anybody been treated by a oncologist that uses chemo sensitivity testing method in choosing chemo drugs/ please post the effectiveness of it in your real life case, thanks.

NancyB - it sounds like even though you had tumor tested for chemo sensitivity that you dont know if it actually helped with your treatment or not. any idea on that/

I have a second question thats sort of related. I stayed up all nite sifting through my fathers medical data bases. It looks like cancer vaccines arec still in various stages of clinical studies. are there any cancer vaccines ready for commercial use ? thanks

Rob

[RandyW]

This is what I have Found about Vaccines.

Lung Cancer

Lung cancer is an area where better treatments are needed, especially for advanced disease. Immunotherapy may help people live longer without the severe side effects sometimes seen with chemotherapy.

A recent study of patients with certain types of non-small cell lung cancer (NSCLC) showed that adding the monoclonal antibody bevacizumab (Avastin) to standard chemotherapy helped them live an average of a couple of months longer than those who got only chemotherapy.

GVAX is an autologous whole cell vaccine. It is made by removing cancer cells from the patient and modifying them to express GM-CSF (to help stimulate the immune system). The cells are then irradiated and given back to the patient. Early studies of patients with advanced NSCLC have shown some responses to this vaccine, but further studies are needed.

BLP25 is a peptide (antigen) vaccine that is encased in a fat droplet (liposome) to make it more effective. A small study of patients with advanced NSCLC suggested it may improve survival time. Larger studies may be needed to confirm this.What Are Cancer Vaccines?

Cancer vaccines are intended either to treat existing cancer or to prevent the development of cancer. Cancer treatment vaccines are designed to strengthen the body's natural defenses against a cancer that has already developed. These vaccines may stop an existing tumor from growing, stop a tumor from coming back after it has been treated, or eliminate cancer cells not killed by previous treatments.

Cancer preventive vaccines are given to healthy people and are designed to target infectious agents that can cause cancer. The hepatitis B virus vaccine is an example of a cancer preventive vaccine. It is used to help prevent liver cancer. Another preventive vaccine that is being studied in clinical trials is a vaccine against human papilloma virus (HPV), which is believed to cause most cases of cervical

[Pam's friend]

I just want to echo Katie's comments about the Doctors at Mary Crowley. Pam is enrolled in the EP-2101 vaccine trial at Mary Crowley and we have had a good experience there.

Many of the vaccines in clinical development are in stage 1/2 trials and consequently are being tested on patients with advanced stages of disease. Unfortuneately, sometimes at that point, the disease has affected the immune system rendering it unable to be "powered" by the vaccine. Also, the vaccines, when effective, tend to take a little bit of time to work.

We were fortunate that Pam's disease, although classified as stage IV, was stable after chemo so she had a functioning immune system and time to respond to the vaccine.

Anyway, for the reasons noted above, it seems that the vaccines will eventually be an even more attractive option for earlier stage patients after an initial round of chemo/radiation. I think that's why the BLP vaccine by Merck was so successful for stage 3b patients.

I believe they are close to starting the large scale stage 3 trial for the Merck BLP vaccine.

[Bill]

my father says that chemo sensitivty testing looks like another example of the in vitro vs in vivo disconnect. nobody here is saying that there oncologist uses this chemo sensitivity testing and I would think that it would be used a lot if it worked.. the slew of doctors and nurses that my father has spoken with which has included a couple of out of state cancer research centers all say that survival time is not really improved with chemo sensitivity testing. they say that most chemo drugs available for a certain type of cancer will work for a time no matter what order you give them and use them up. in fact in my mothers case 2 of the 3 drugs being used right now are previouisly used drugs that have failed which my father wasnt happy about but believe it or not they seem to be working in this new combination. at least for now working well enough to keep my mother alive and hold back further lung damage. and she isn;t the only one. this is a new treatment trend along with Tarceva in our area according to what I am told. so much for the theory that failed chemo drugs cant be reused. the good news is that it looiks like failed drugs can be resued if they are reused in new treatment combinations

rob

[karen335]

http://www.welcomefunds.com/viatical-settlements.htm

Rob,

Not sure if I posted this in the right place...

It explains how life insurance can be used to pay for treatment for a terminal illnes. If nothing else, it's worth a read...

Prayers for your mom,

Karen in So. California too

[gpawelski]

Bill

Oncologists prescribe patients one standard empiric chemotherapy regimen after another, until they find one that works. This often can expose patients to the side effects of chemotherapy, without showing any cancer-killing results. Guesswork can be done in a laboratory instead. Assay-testing is based on a biological principle that when a drug is effective, it will induce cell-death (apoptosis) in the cancer cell. If the cancer cell is resistant to a drug, apoptosis will not occur. Assay-testing for apoptosis will determine whether a drug kills the tumor. And this can lead to increased survival time.

The American Society of Clinical Oncology points out that tests are useful only if the information they produce leads to patient management changes that improve outcomes, such as longer survival, better quality of life, or fewer adverse events. Until the controlled, randomized trial approach has delivered curative results with a high success rate, the choice of physicians to integrate promising insights and methods like chemosensitivity testing remains an essential component of this kind of treatment advocacy.

Because the number of available chemotherapeutic agents has increased enormously over the past few years, the emphasis on the rationale for these assays has never been stronger. As the number of possible treatment options supported by completed randomized trials increases, the scientific literature becomes increasingly vague for guiding physicians. Almost any combination therapy is acceptable in the treatment of cancer these days.

Physicians are confronted on nearly a daily basis by decisions that have not been addressed by randomized trial evaluation. Their decisions are made according to experience, new basic science insights, bias or personal preference, philosophical beliefs, etc.. With all these uncertainties, would it be wrong to make a clinical decision based on assay testing? Should it be denied to patients who walk in the door asking for it? Patients who want this testing, after a thorough discussion about the peer-reviewed studies and experience that supports it, should not be hindered by restrictive policy.

With the absence of effective laboratory tests to guide physicians, many patients do not even get a second chance at treatment when their disease progresses. Spending six to eight weeks to diagnose treatment failure often consumes a substantial portion of a patient's remaining survival, not to mention toxicities. In cases where there are several equivalent treatments available, patients can benefit from assay test results as a supplement to other clinical data when deciding on a treatment option.

Having some foreknowledge of a given chemo agent's expected result before its administration would benefit the individual patient. The cost of drugs is enormous. Patients are followed with serial CT scans, MRI's and even Pet Scans, just to see if a tumor is growing or shrinking. Not to mention the hospitalizations for toxicity, bone marrow tranfusions, etc. The point is, the cost of ineffective therapy is truly enormous and assay-testing is particularly good at identifying ineffective therapy.

The heterogeneity of human cancer is shown both by the fact that some patients derive great benefit from treatments which fail to help (and often harm) the majority of patients who receive the treatment. And many patients fail to benefit from 1st line chemotherapy, only to derive great benefit from 2nd or even 3rd line chemotherapy. These patients should have received the correct treatment the first time around. Everyone would agree that the earlier in the course of the disease that the most active treatment is given, the better the result for the patient.

Assay testing is a process of testing chemotherapy drugs on a patient's tumor cells to see if the drugs might or might not have any effect on the tumor. By testing the tumor cells, 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 trials.

[Bill]

Greg - I will reply cuz the question was put out by me not my father and he is seldom home these days. we understand the testing theory and it sounds very promising. the problem is what usually happens in the lab compared to actual medical practice. the results seen in the lab arent reproduced that effectivwely in actual medical practice on real patients. I wish it werent so cuz my mother would benefit but 1 oncology dr after anotehr says the same thing. chemo sensitivity testing doesnt help much to extend survival time. just reshuffles the chairs. might also be do to the fact that most patients arent diagnosed til later stages. my moms oncologist said that he will send a sample of her next pleural effusion for chemo testing if she requests it but he doesnt expect it to make much difference in her survival time. I spoke with 1 of the main chemo lab experts in southern cal.. he said that except for the navelbine strength < reduced do to the combination of drugs > that the chemo mix that my mother is on right now sounds good to him

rob

[gpawelski]

Rob

It is true that what happens in the lab is not necessarily what happens in the patient. Individual testing of patients are not scale models of chemotherapy in the patient, anymore than the barometric pressure is a scale model of the weather. But it's always more likely to rain when the barometer is falling than when it is rising, and chemotherapy is more likely to work in the patient when it kills the patient's cancer cells in the laboratory. It's no different than any other medical test in this regard.

The only role that chemosensitivity testing plays is that it seems entirely reasonable that effective, although mutagenic therapy would be preferred over ineffective, mutagenic therapy. Chemotherapy not only causes mutations, which might make a given cancer more agressive, but it causes second malignancies as well.

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. Metastasis is an organism-wide phenomenon that may involve dozens of processes. It's hard to do replicable experiements when there are so many variables. So, instead, researchers opt for more straightforward experiments that generate plenty of reproducible results (like tumor shrinkage).

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.

A chemo-induced gene mutation can happen when the original chemo received does not work. The cancer comes back. When it does this, the cancer comes back more aggressively. The mutagenic effects (changes in form) of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior. You might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion. Like when chemotherapy on an ER+ cancer brings about a remission, but in the process also causes any remaining cancer to become ER-.

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. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them. I just feel the we cannot afford more "trial and error" treatment.

Blessings to you and your family.

[gpawelski]

From Medicineworld.org: Cancer News Blog

Researchers at Karolinska Institutet in Sweden have helped to identify a molecule that can be used as a vaccination agent against growing cancer tumours. Eventhough the results are so far based on animal experiments, they point to new methods of treating metastases.

The results are presented in the online edition of the prestigious scientific journal Nature Medicine, and represent the collaborative efforts of scientists at KI and Leiden University Medical Centre in Holland.

The study analysed an immunological cell, a T cell, which recognises other cells with defects common to metastasing ones. These defects (which are found in MHC class 1 molecules) allow the tumour cell to evade the "conventional" T cell-mediated immune defence.

The scientists have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the scientists can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.

"So far we've only conducted research on mice, so it's too early to get out hopes up too much," says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. "However, the study does point towards new possible ways of developing a therapy for advanced tumour diseases."

The newly published study is a continuation of an original discovery that first identified the TEIPP-T cell and that was presented in Ms Wolpert's doctoral thesis at Karolinska Institutet in 1998.

The spread of tumours, or metastases, is the most common cause of death from cancer.

[Bill]

Greg >> 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.

Greg - this stqatement of yours is exactly what we are coming up against. this is also the explanation given why tumor shrinkage doesnt have much to do with survival time. 1 oncologist told us that chemo testing would be very valuable if there was a pool of chemo drugs availsble that contained some drugs that cured cancer not just delayed progression of the cancer. this is the main reason given why they are not excited asbout chemo testing right now. reshuffling the order doesnt help much

rob

[gpawelski]

Boy! The oncologist is really washing his hands of it.

"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. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them."

Even M.D. Anderson Cancer Center is now taking a new look at how to evaluate new medicines and treatments for cancer. They are adopting the Bayesian method of science in more than 100 cancer-related phase I and II clinical trials being planned or carried out, because the Bayesian method of science is more in line with how science really works.

Chemosensitivity testing is most accurate thanks to the Bayesian methology. The method is no stranger to cell culture assasy testing. In fact, it is what gives credit to the accuracy of these tests.

[Alisa]

I have to say that the three oncs that I have spoken to about this all say the same thing that Rob is saying. But I think they are making progress in that field ....

[gpawelski]

There certainly is resistance to this approach from some oncologists, but no one has ever shown that harm could result from the use of these technologies and there is a considerable body of evidence to support their use. The tests provide a valuable research resource and have been used to develop new drugs for cancer.

I seriously doubt that many "on the floor" oncologists have any understanding whatsoever of the "current" technologies of chemosensitivity testing (like clinical oncologists), which are based on "cell-death" and not "cell-growth." Some are slow to change. There are many very intelligent people who are working every day to bring these technologies to reality.

What I hear here reminds me of "The Discoverer" post. Two Australians won the Nobel Prize in medicine for proving that bacteria and not stress was the main cause of painful ulcers of the stomach and intestine. How many loved-ones had died of a bleeding ulcer? They would have been cured permanently by a two week course of antibiotics. And the two Aussies did it over the dead body opposition of the entire world of medicine and the pharmaceutical industry. Ah! the mindset of rewarding academic achievement and publication over all else.

This is a perfect example of thirty-five years of the trail-and-error mind-set that has occupied cancer research. The cancer "investigator" culture that prizes itself on the exhaustive examination of trivial hypotheses, while eschewing support of cancer "discoverer" type research, attempting to create entirely new paradigms of cancer treatment. A dysfunctional 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 achievment and publication even though their proven "activity" has little to do with curing cancer.

Over at www.cancerselfdefense.com they have a pretty good saying, "If your current Doctor hasn't done it, do it yourself (then find a better doctor)."

[kiams]

I paid for chemo sensitivity testing after my last surgery. My Oncologist thought I was wasting my money, however, he ended up selecting the same drug shown by the lab to have the best result against my tumor. It was expensive, but it gave me peace of mind.

[Alisa]

I read an article written by a cancer patient that had this testing done and it showed she would not respond to a particular chemo cocktail. She went ahead with it anyway, cause it was the protocol treatment at her hospital and she had full response. Had she listened to the sensitivity test, she would not have used this treatment. She is currently NED. I don't remember all the details, but I think the article was posted here at lchelp.

[Bill]

I read an article written by a cancer patient that had this testing done and it showed she would not respond to a particular chemo cocktail. She went ahead with it anyway, cause it was the protocol treatment at her hospital and she had full response. Had she listened to the sensitivity test, she would not have used this treatment. She is currently NED. I don't remember all the details, but I think the article was posted here at lchelp.

A :

This was one of the criticisms that I heard from some of the med oncs and OCNs that I spoke with re: chemosensitivity testing. Chemotherapeutic agents that were ruled out based on chemosenstivity testing, as well as previously failed in practice, are being reused in different tx combinations with varying degrees of success. Most of this defies what I know about pharmacology, synergism, etc. but oncology is full of unknowns. My wife's current chemo cocktail looks like a loser on paper but she is still alive and now off of oxygen. So, obviously there's been some improvement in her respiratory function since starting this new tx regimen. When I confronted her med onc about this he confidently replied that he expected a favorable response based on trial and error with this and similar combos. Also, this type of therapeutic action unhinges the long-standing theory in oncology that failed chemotherapeutic agents can't be successfully reused.

B

[gpawelski]

kiams

Besides the assays predicting which chemotherapy drugs will work best for the patient, they can also end up confirming that the standard treatment is the best option.

Multiple drug therapy does not seem to confer an advantage over single agent treatment, however, combination chemotherapy frequently, but not always, has produced degrees of clinical benefit than single agent therapy.

There are two potential explanations for this. First, when two or more drugs are given, there is a greater probability that at least one of the drugs will be active (synergistic to the tumor). Second, there is the potential for true synergy, where the whole is greater than the sum of the parts.

[gpawelski]

Bill

In regards to "trial and error" treatment, whatever clinical response that has resulted to the average number of patients in a randomized trial, is no indication of what will happen to an individual at any particular time. They are trying to identify the "best guess" treatment for the average patient. You cannot mate notoriously heterogeneous diseases into "one-size-fits-all" treatments.

While new chemotherapy regimens "appear" to be improving survival, when these same regimens are tested on a wider range of cancer patients, the results have been disappointing. In other words, oncologists at a single institution may obtain a 40% - 50% response rate in a tightly controlled study, but when these same chemotherapy drugs are administered in a real world setting, the response rates decline to only 17% - 27%.

Because of this, patients respond differently to the same anticancer drugs. Your treatment should be tailored to your cancer, not your cancer tailored to your treatment.

[Alisa]

So, with all this information, it still seems to me that chemo sensitivity testing is a waste at this time. But I think we've come far in this area and hopefully they will perfect the test soon. And when they do, I bet we, on this board, will be the first to know.

[gpawelski]

Alisa

Chemosensitivity testing is not a waste of time. Laboratory screening of samples from a patient's tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents. Besides the assays predicting which chemotherapy drugs will work best for the patient, they can also end up confirming that the standard treatment is the best option, and like with kiams, give a peace of mind.

Like I've said above, chemosensitivity testing has been perfected thanks to the Bayesian methology. The method is no stranger to cell culture assay testing. It is what gives credit to the accuracy of these tests. Even M.D. Anderson is taking a new look at how to evaluate new medicines and treatments with this methology, because the Bayesian method of science is more in line with how science really works.

[Alisa]

Right, I understand all that. But what about the instances where the test said a treatment would not be effective, but in fact, was effective and patients showed great response and/or are NED after the same treatment the test said would be ineffective? That's all I meant when I said in my opinion, I think it pays to wait until it is more accurate but I would never 100% rule anything out. But I think this is a GREAT START and I am very excited to see how this all develops.

Thanks you so much for all the information.

[Bill]

Right, I understand all that. But what about the instances where the test said a treatment would not be effective, but in fact, was effective and patients showed great response and/or are NED after the same treatment the test said would be ineffective? That's all I meant when I said in my opinion, I think it pays to wait until it is more accurate but I would never 100% rule anything out. But I think this is a GREAT START and I am very excited to see how this all develops.

Thanks you so much for all the information.

A :

I'd summarize the current status of chemosensitivity testing this way. Assuming that a reliable correlation b/w in vitro ( lab ) test results and in vivo ( patient ) response does exist, chemosensitivity testing, at this stage of knowledge, would better organize chemo tx and tumor response ( shrinkage ). Unfortunately, until a cure is found, a better organized tx regimen with improved tumor shrinkage does not correlate with a clinically significant improvement in survival time. IMO, an experienced med onc with lots of trial and error experience with various combination chemo regimens can most likely administer a tx regimen that is at least comparable in survival time to what you'd get by strictly adhering to chemosensitivty testing results. Possibly a better result could be obtained by the experienced med onc if you consider the possibility that drugs ruled out by chemosensitivity testing may have tx value if administered in the right combination(s). I, for one, prefer that my wife's med onc try any chemo combination, no matter how ineffective it appears on paper, if he is confident, based on experience, that said chemo combination has tx value. Individualized tx theory has merit but it's not etched in stone.

B

[gpawelski]

Laboratory tests are judged by "accuracy" and "reproducibility" and never by their effect upon treatment outcomes. Improved outcome studies of laboratory tests are never carried out. Most tests used today in oncology have comparable "sensitivities" and "specificities."

Pet Scans were not approved because they saved lives in a controlled clinical trial that compared the outcome of patients who received care with or without the benefit of a Pet Scan. They were approved because their performance characteristics (sensitivity/specificity) are reproducible, favorable and provide useful information to treating physicians.

Sensitivity and specificity are terms that apply to test accuracy. No test in oncology, including imaging studies such as MRI’s and PET scans, has ever been shown in a prospective randomized clinical trial to improve patient outcomes.

The existing standard has always been the accuracy of the test. This is true for every single test used in cancer medicine, from estrogen receptors to panels of immunohistochemical stains to diagnose and classify tumor to Her2/neu and CA-125 to cell culture assays to MRI Scans, CT Scans, Pet Scans and on and on.

Because Pet Scans are accurate and reproducible and because they correlate reliably with the clinical or biological phenomena which they are intended to detect or measure, many such tests are considered invaluable.

A cell culture assay is the one test in oncology which has the greatest immediate potential to improve therapy selection for "individual" patients. Data from studies demonstrate close correlation between prospective predictions of drug activity and patient chemotherapy response, and overall survival.

When individual patients are treated with drugs "active" in cell-death assays, they have vastly superior response and survival rates than when they are treated with drugs which are "not active" in the assays.

There is no proven "standard" first line therapy which has been shown to be superior to the many other choices which exist. The therapies are equivalent on a "population" basis, but not on an "individual" basis. Patients should have the "correct" treatment in the first line setting. This can be accomplished by individualizing cancer treatment based on testing the cancer biology.

Upgrading clinical therapy by using drug sensitivity assays can improve the "conventional" and "targeted" situation by allowing more drugs to be considered. The key to improving drug sensitivity tests is related to the number and types of drugs tested. The more cancer drug types there are in the selective arsenal, the more likely cancer medicine is to prove beneficial.

Every cancer patient should have his/her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of drug sensitivity assays are being encouraged by growing patient demands, scientific advances and medical ethics. Drug sensitivity tests are a powerful strategy that cannot be overlooked.

[Bill]

The American Society of Clinical Oncologists (ASCO) and their affiliated investigators/reviewers have been of the opinion, based on preconceived bias and not on any actual data, that it is impossible to take freshly biopsied human tumors, place them in tissue culture, and obtain any useful information whatsoever concerning the likelihood of different drugs working against the very same tumor in the patient.

The have not only refused to support work in this field, but they have also done everything within their power to extinguish work in this field. In their review, they specifically excluded from consideration all published studies which documented test accuracy (not efficacy), the only criterion used to validate any test currently used or ever used, in all of cancer medicine.

It's one of the greatest lost opportunities in all of cancer medicine, and the efforts to extinguish work in this area continue unabated, because ASCO refuses even to look at data showing that patients are 7 times more likely to benefit from treatment with assay-tested "active" drugs than from treatment with assay-tested "inactive" drugs, in scores of studies, involving thousands of patients, in lieu of a misguided quest to identify the best treatment for the average patient through unproductive clincial trials of empiric therapies.

We can do better!

G :

I think that you've essentially answered your own question. Based on my search for medical opinion on utilizing chemosensitivity testing it's been a wholesale rejection of this technology from those questioned. The reasoning is as I have laid out in my previous posts including numerous personal contacts and clinical opinion such as this one :

http://www.aetna.com/cpb/data/CPBA0245.html

Another limitation is that the typical private practice med onc simply doesn't have that many suitable chemotherapeutic drugs in his or her arsenal to fight a given cancer. Any competent med onc will very likely make an effort to utilize all of these suitable drugs on a given patient and should be able to utilize them in a reasonably intelligent rationing order. Assuming in vitro vs. in vivo reliability ( which, as you state, is a questionable issue ), I can envision this testing being more beneficial when the day comes that a med onc has a very large group of suitable drugs ( including some curative ) available for a given cancer patient. We will just have to wait and see how med oncs deal with cures when that day hopefully comes.

B

[gpawelski]

Medicare Contractor Establishes Reimbursement Coverage Policy for Cell Culture Assay Tests

National Heritage Insurance Company (NHIC), the contractor that administers Medicare programs in California, has established a positive coverage policy for Cell Culture Assay Tests known as Chemosensitivity (Resistance) Testing or Oncologic In Vitro Chemoresponse Assays for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within Southern California. Medicare bills for this testing are billed through NHIC because the test is conducted by the approved laboratories in California.

This pre-test can help see what treatments have the best opportunity of being successful for "high" risk cancer patients. The test measures the response of "live" tumor cells to drug exposure. Following this exposure, the assays measure both cell metabolism and cell morphology (Functional Profiling). The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. Assays based on "cell-death" occur in the entire population of tumor cells.

This cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses "fresh" human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients.

Following the collection of "fresh" tumor cells obtained from surgery or tru-cut needle biopsies, a cell culture assay is performed on the tumor sample to measure drug activity (sensitivity and resistance). This will pinpoint which drug(s) are most effective. Tissue, blood, bone marrow, and ascites and pleural effusions are possibilities, providing tumor cells are present. At least one gram of fresh tissue is needed to perform the tests, and a special kit is obtained in advance from the lab. The treatment program developed through this approach is known as assay-directed therapy.

Individualized assay-directed therapy is based on the premise that each patient's cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.

The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they abandoned the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit. Drug "sensitivity" testing is merely a point a little farther along on the very same continuum which "resistance" testing resides.

Cell cuture assay tests based on "cell-death" have proven very effective in identifying novel treatment combinations for a variety of cancers. The value of cell-death assays is that they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. It can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

The current clinical applications of in vitro chemosensitivity testing is ever more important with the influx of new "targeted" therapies. Given the technical and conceptual advantages of "functional profiling" of cell culture assays together with their performance and the modest efficacy for therapy prediction on analysis of genome expression, there is reason for renewed interest in these assays for optimized use of medical treatment of malignant disease.

The payment provided will be sufficiently realistic that all Medicare patients for whom this testing is indicated will be able to get it with only the routine 20% co-payment, as Medi-gap insurance secondaries are mandated to provide payment for co-pays for Medicare-approved services.

The coverage became effective for claims for services performed on or after February 19, 2007. The decision is posted at:

http://www.medicarenhic.com/cal_prov/ar ... t_0107.htm

NHIC Medicare Services reimburses qualified laboratories in Southern California for cell culture assay tests on a Medicare patient anywhere in the United States.

Likewise, Highmark Medicare Services reimburses a qualified laboratory in Pennsylvania for cell culture assay tests on a Medicare patient anywhere in the United States.

NHIC has jurisdiction over Southern California, so that is who gets billed when the laboratory is located in California.

Highmark has jurisdiction over laboratories in Pennsylvania, so that is who gets billed when the laboratory is located in Pennsylvania.

The coverage decision is posted at:

http://www.highmarkmedicareservices.com ... 32007.html

It amazes me not only that some private insurance carriers don't like to pay for cell culture assay tests but that they don't emphatically mandate it as a requirement for obtaining chemotherapy reimbursement against ill-directed treatments.

The validation standard that private insurance companies is accepting from "molecular" profiling tests is "accuracy" and not "efficacy." The "bar" has been instantly lowered. No longer will it be essential to prove that the use of a diagnostic test improves clinical outcomes, all they have to do for these "molecular" profiling tests is prove that the test has a useful degree of "accuracy." However, at the same time, the validation standard they want for "cell-based" profiling tests is "efficacy."

The "cell-based" profiling tests have the same entitlement to be judged by the same validation standard as "molecular" profiling tests. The combination of measuring morphologic (structural) effects and metabolic (cell metabolism) effects constitutes measuring the "profile" at the whole cell level. It must be noted that both types of dignostic tests are just that, "tests" and not treatment.

Profit, as we have seen, is a powerful motivating force. Among the private payors, at least, the profit motive is entirely consistent with the goal of the test, which is to identify efficacious therapies irrespective of drug mark-up rates.

The evidence in support of these assays is more than sufficient to justify the funding of validation trials, if any more truly are needed, as claimed - speciously and self-servingly - by the medical establishment.

Everyone is scared to death - and rightly so - at what is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs that benefit only a small percentage of patients who receive them, hence the headlong rush to develop tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient.

Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class, such as Sutent, Tarceva, Iressa, and Nexavar.

The FDA could benefit too, as they find themselves under increasing pressure to allow new drugs into marketplace while at the same time protecting the safety of potential recipients of those drugs as well as the financial interests of those who will have to pay for them.

It explains the new paradigm of requiring a companion diagnostic as a condition for approval of new targeted therapies. The pressure, in fact, is so great that the companion diagnostics they've approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

I think that in both of these areas - private insurance carriers and the FDA - there is a very real opportunity to make a substantial impact and contribution, an interest in saving the healthcare system perhaps billions of dollars a year (and thereby the healthcare system itself) by ensuring that expensive treatments are used appropriately.

Committee chairpersons, committee members and persons in congress who may have personal interests not only in discovering new cancer treatments - everybody wants that - but also, in the "here and now," using currently-available cell culture assay technologies to improve the effectiveness of existing drugs and save lives today by administering the right drug to the right patient at the right time.