Chemosensitivity testing

MarkF
MarkF Member Posts: 3
edited March 2014 in Lung Cancer #1
I am trying to raise awareness of chemoresistance/sensitivity testing as a result of my own success with this screening method. I am a 42 yo male, non-smoker who was diagnosed in may 2003 with NSCLC stage 3b. I insisted on having my tumor screened before I began chemo and had a lymph node removed to provide the sample for the test. The testing takes your cancer cells and incubates them in the presence of the drugs the doctors would consider giving you and with some they may not normally consider. The premise is that if in a test tube the presence of the chemo cant kill your cancer cells, at a higher concentration than can be delivered to the patient, then there is little chance that therapy will work in you the patient. The screen is apparently very good at identifying inactive drugs which can save a patient with little time from picking a non-working drug. The contention comes in the ability of the screens to pick effective therapies. I, however, am now a firm believer in this area. My own treatment was directed by the results from my screen. Normal first line taxol cisplatin therapy was inactive in my screen so I avoided that and went instead with the only combination of drugs from the 20 odd therapies tested that did show some tumor cell killing ability. I finished up on a Gemzar, carboplatin, navelbine, high dose Tamoxifen and iressa protocol. After 4 cycles my PET scan is clean, I have no detectable active tumor, and we will not be doing radiation!! My oncologist is stunned and I think is now a convert as to the usefullness of these screens. Whenever I talk to other patients and doctors nobody has ever heard of these tests. A good starting point for information is www.weisenthal.org where I had my tests done Dr Weisenthal has some good background information available on his site. I encourage everyone to at least have a look at this before your next choice of chemo and please fell free to contact me with any questions.
Best Regards
Mark

Comments

  • cbecker
    cbecker Member Posts: 88
    Hi Mark: my husband had this done too but it was after the fact because his doctor here did not do it. He had throat cancer and got rid of that tumor but unfort. it metastasized to lungs he had squamous cell. After 40 radiation treatments to neck that got that tumor but did not check his lungs so he had 12 tumomrs in both. He went thru chemo of cisplatin and taxol and 5fu (clincial trial) and the 5fu brought back radiation recall so just went on cisplatin and taxol. Did not respond so went elsewhere and they did the study. Taxol was the worse one for response to his cancer so he lost his hair and the worse thing is he has bad neuropathy from the taxol. So now they put him on a trial for Iressa. He has to go on trial because it is met. cancer to lungs and fda just approved it for primary lung (I think that is way) He has his follow up lung scan on Oct 23rd to see if Iressa is working. So I do know how important it is to have the chemosensitivity testing done, just wish we knew about it sooner. Thank you for posting this. Prayers to your continued success, hope ours will be the same. It has been a rough almost two years and cancer has run our lives. Thanks, Candy
  • ann330101
    ann330101 Member Posts: 4
    cbecker said:

    Hi Mark: my husband had this done too but it was after the fact because his doctor here did not do it. He had throat cancer and got rid of that tumor but unfort. it metastasized to lungs he had squamous cell. After 40 radiation treatments to neck that got that tumor but did not check his lungs so he had 12 tumomrs in both. He went thru chemo of cisplatin and taxol and 5fu (clincial trial) and the 5fu brought back radiation recall so just went on cisplatin and taxol. Did not respond so went elsewhere and they did the study. Taxol was the worse one for response to his cancer so he lost his hair and the worse thing is he has bad neuropathy from the taxol. So now they put him on a trial for Iressa. He has to go on trial because it is met. cancer to lungs and fda just approved it for primary lung (I think that is way) He has his follow up lung scan on Oct 23rd to see if Iressa is working. So I do know how important it is to have the chemosensitivity testing done, just wish we knew about it sooner. Thank you for posting this. Prayers to your continued success, hope ours will be the same. It has been a rough almost two years and cancer has run our lives. Thanks, Candy

    Hi Cindy,

    My dad was diagnosed w/Lung Cancer in June and it has been a very hard time for my family and I, as I am sure you understand. He just finished 6 treatments on Taxol and also has bad neuropathy in his feet and he is very tired. It was shrinking the cancer a little, but his doctor said he now has to wait until January to continue, because of the side effect and harshness of the Taxol..They may give him a different medication in January. Does the numbness of the feet ever go away after being off the chemo?

    Thanks.
  • gdpawel
    gdpawel Member Posts: 523 Member
    ann330101 said:

    Hi Cindy,

    My dad was diagnosed w/Lung Cancer in June and it has been a very hard time for my family and I, as I am sure you understand. He just finished 6 treatments on Taxol and also has bad neuropathy in his feet and he is very tired. It was shrinking the cancer a little, but his doctor said he now has to wait until January to continue, because of the side effect and harshness of the Taxol..They may give him a different medication in January. Does the numbness of the feet ever go away after being off the chemo?

    Thanks.

    When a patient has an infection, doctors often send a sample of infected blood or tissue to a lab where they can grow the bacteria and see which antibiotics are most effective (called Bacterial Culture and Sensitivity Testing). Chemosensitivity testing is an attempt to do something similar for cancer; fresh samples of the patient's tumor from surgery or a biopsy are grown in test tubes and tested with various drugs. Drugs that are most effective in killing the cultured cells are recommended for treatment. It is highly desirable to know what drugs are effective against your particular cancer cells before highly-toxic agents are systemically administered to your body.

    One approach to individualizing patient therapy is chemosensitivity testing. Chemosensitivity assay is a laboratory test that determines how effective specific chemotherapy agents are against an individual patient's cancer cells. Often, results are obtained before the patient begins treatment. This kind of testing can assist in individualizing cancer therapy by providing information about the likely response of an individual patient's tumor to proposed therapy. Chemosensitivity testing may have utility at the time of initial therapy, and in instances of severe drug hypersensitivity, failed therapy, recurrent disease, and metastatic disease, by providing assistance in selecting optimal chemotherapy regimens.

    All available chemosensitivity assays are able to report drug "resistance" information. Resistance implies that when a patient's cancer cells are exposed to a particular chemotherapy agent in the laboratory, the cancer cells will continue to live and grow. Some chemosensitivity assays also are able to report drug "sensitivity" information. Sensitivity implies that when a patient's cancer cells are treated with a particular chemotherapy agent in the laboratory, that agent will kill the cancer cells or inhibit their proliferation.

    The goal of all chemosensitivity tests is to determine the response of a patient's cancer cells to proposed chemotherapy agents. Knowing which chemotherapy agents the patient's cancer cells are resistant to is important. Then, these options can be eliminated, thereby avoiding the toxicity of ineffective agents. In addition, some chemosensitivity assays predict tumor cell sensitivity, or which agent would be most effective. Choosing the most effective agent can help patients to avoid the physical, emotional, and financial costs of failed therapy and experience an increased quality of life.

    Fresh samples of the patient's tumor from surgery or a biopsy are grown in test tubes and tested with various drugs. Drugs that are most effective in killing the cultured cells are recommended for treatment. Chemosensitivity testing does have predictive value, especially in predicting what "won't" work. Patients who have been through several chemotherapy regimens and are running out of options might want to consider chemosensitivity testing. It might help you find the best option or save you from fruitless additional treatment. Today, chemosensitivity testing has progressed to the point where it is 85% - 90% effective.

    Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual. For many cancers, especially after a relapse, more than one standard treatment exists. There is rarely a situation where you would get everyone to agree that there's only one form of therapy. Physicians select drugs based on their personal experience, possible side effects and the patient's condition, among other factors. The system is overloaded with drugs and underloaded with wisdom and expertise for using them.

    Chemosensitivity testing might help you find the best option, or save you from fruitless additional treatment. Another situation where chemosensitivity testing might make particularly good sense is in rare cancers where there may not be enough experience or previous ideas of which drugs might be most effective.

    Finally, there has been a veritable deluge of new approvals of cytotoxic drugs in recent years as the tortuous FDA process has been speeded and liberalized. In many cases a new drug has been approved on the basis of a single very very narrow indication. But these drugs may have many useful applications - and it's going to take years to find out. Chemosensitivity testing offers a way of seeing if any of these new drugs might apply to your specific cancer.

    Another Name

    Cell Culture Drug Resistance Testing (CCDRT) or Chemotherapy Sensitivity and Resistance Assays (CSRAs) refers to laboratory testing of a patient's own cancer cells with drugs that may be used to treat the patient's cancer. A group of lab tests known as Human Tumor Assay Systems (HTAS) can aid oncologists in deciding which chemotherapies work best in battling an individual patient's form of cancer. The assay is a lab test performed on a biopsy specimen containing living cancer cells. It's used to determine the sensitivity or resistance of malignant cells to individual chemotherapy agents. Depending on how well the tumor cells respond to each chemotherapy agent, they are rated as sensitive, resistant or intermediate to chemotherapy. The concept is that you are better off using a chemotherapy drug that your tumor reacts to strongly than one your tumor resists.

    There have been over 40 publications in peer-reviewed medical literature showing correlations between cell-death assay test results and the results of clinical chemotherapy in more than 2,000 patients. In every single study, patients treated with drugs active in the assays had a higher response rate than the entire group of patients as a whole. In every single study, patients treated with drugs inactive in the assays had lower response rates than the entire group of patients. In every single study, patients treated with active drugs were much more likely to respond than patients treated with inactive drugs, with assay-active drugs being 7 to 9 times more likely to work than assay-inactive drugs. A large number of peer-review publications also reported that patients treated with assay-tested "active" drugs enjoyed significantly longer survival of cancer than patients with assay-tested "negative" drugs.

    Listing of "Reputable" Labs USA:

    These labs will provide you and your physician with in depth information and research on the testing they provide.

    Analytical Biosystems, Inc., Providence, Rhode Island. 1-800-262-6520

    Anticancer, Inc., San Diego, CA. 1-619-654-2555

    Cancer Therapeutics, Inc., Thomasville, GA. 1-229-224-6839

    DiaTech Oncology, Brentwood, TN. 1-615-294-9033

    Genomic Health, Inc. Redwood City, CA. 1-650-556-9300

    Genoptix, Inc., San Diego, CA 1-858-523-5000

    Human Tumor Cloning Laboratory, San Antonio, TX. 1-210-677-3827

    Impath, Inc., New York, NY. 1-800-447-8881

    Nu Oncology Labs, Virginia Beach, VA. 1-757-554-0926

    Oncotech, Inc., Irvine, CA. 1-714-474-9262 / FAX 1-714-474-8147

    Oncovation LLC, New York, N.Y. 1-212-514-2422

    Precision Therapeutics, Pittsburgh, PA. 1-866-243-6639

    Rational Therapeutics Institute, Long Beach, CA. 1-562-989-6455

    Sylvester Cancer Institute, Miami, FL. 1-305-547-6875

    Weisenthal Cancer Group, Huntington Beach, CA. 1-866-364-0011

    How May a Patient Arrange to Have Their Tumor or Leukemia Tested?

    Both fluid and solid tumor (200mg in size) specimens may be sent out via Federal Express or another overnight courier service for testing at one of more than a dozen labs around the country. Note that the choice of a lab is not a geographical consideration, but a technical consideration. All of the labs that are listed are experienced and capable of providing very useful information. However, the labs vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. These private laboratories have been offering these assays as a non-investigational, paid service to cancer patients, the average cost being about $2,000, in a situation where 20 different drugs and combinations are tested, at two drug concentrations in three different assay systems.

    Assay-tests could be performed from ovarian cancer cells in pleural fluid (fluid from the cavity that surrounds the lungs) which is evidence of Stage IV ovarian cancer, or from Ascites (an abnormal accumulation of fluid in the abdomen), and of course lymph nodes. A worse case scenario is the spinal fluid (spinal tap) but only to diagnose Leptomeningeal Carcinomatous (ovarian). The labs will provide you and your physician with in depth information and research on the testing they provide.

    By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to the patient's own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered.

    Some Resistance

    The fact that some doctors don't agree isn't stopping many cancer patients from taking this matter into their own hands, and sending their live path specimens off to one of the above private labs for assay-testing to be done. In fact, approximately 10,000 individual patient specimens are currently being submitted for testing by more than 1,000 clinical oncologists, surgeons and pathologists annually in the United States. There has been much discussion about whether assay (in vitro) tests are of any use, as the in vivo response to a drug may very well be different in the body than in the petri dish. But, they said the same for Bacterial Culture and Sensitivity Testing. Doctors cannot remember a time when they didn't have this technology. It is a 'gold' standard. So will Chemosensitivity Testing.
  • gdpawel
    gdpawel Member Posts: 523 Member
    The traditional criteria ever used to evaluate laboratory tests has been the predictive 'accuracy' of the test.

    None of the available laboratory tests used in the selection of treatments for cancer patients have ever been tested for 'efficacy'. This includes estrogen receptor, progesterone receptor, Her2/neu, immunohistochemical staining for tumor classification, bacterial culture and sensitivity testing, CT, MRI and FDG Pet Scans to measure tumor response to treatment.

    There is no literature establishing clinical 'efficacy' of these laboratory tests, because the costs of such clinical trials are prohibitive, granting agency support is non-existent, and no other analogous tests have been or will likely ever be subjected to such an unreasonably high bar criterion for clinical use.

    The only data supporting any of them relate to test 'accuracy', and there is a total lack of information regarding test 'efficacy'. (randomized trials with outcome measurements for diagnostic tests)

    Also, no one is seriously proposing that any of the molecular tests now available (Oncotype DX, EGFR amplification/mutation) should have to be proven 'efficacious', as opposed to merely 'accurate', before they are used in clinical decisions regarding treatment selection.

    The American Society of Clinical Oncology (ASCO) reviews of cell culture assay tests for establishing clinical 'efficacy' specifically excluded all studies reporting the predictive 'accuracy' of the tests. In other words, they excluded reports that only reported correlations between assay results and clinical outcomes.

    Instead, ASCO reviews included old, previously-reviewed studies comparing outcomes of patients who had treatment based on assay results versus patients with empirically chosen therapy. The criteria of laboratory assay 'efficacy', as opposed to laboratory assay 'accuracy' sound reasonable, but it is unprecendented with regard to any other laboratory test ever evaluated.

    Cell culture assay tests have been well proven to have predictive 'accuracy' with that of estrogen receptor, progesterone receptor, Her2/neu and the newer molecular tests. In light of the precious little in the way of guidance from clinical trials with respect to best empiric therapy (where the only thing that has been proven to correlate with treatment decisions is reimbursement to the prescribing oncologist) and the importance of basing cancer treatment at least in part on patient preferences, it is entirely reasonable to support judicious application of laboratory tests which have been well characterized with respect to test 'accuracy'. These are diagnostic tests and should be held to that criteria, and not to that of therapy.

    These laboratory tests are a tool for the oncologist. The oncologist should take advantage of all the tools available to him/her to treat a patient. And since studies show that only 25-30% of patients do respond to chemotherapy that is available to them, there should be due consideration to looking at the advantage of human tissue assay tests to the resistance that has been found to chemotherapy drugs.

    Cell culture drug resistance testing is for preventing use of known anti-cancer drugs that are not likely effective in the specific tumor. Cell culture drug sensitivity testing tries to determine specific drug and dose effectiveness. The distinction between sensitivity and resistance is more semantic than substantive.

    In virtually all forms of cancer, clinical trials have failed to identify best drug regimens for use in all individuals with a given form of cancer.

    Oncologists have been documented to use reimbursement (payment to the oncologist) as the most important criterion for selecting between the large array of otherwise equally acceptable regimens. (Jacobson, M.,O'Malley, A.J., Earle, C.C., et al. Health Affairs 25(2):437-443, 2006) & (Patterns of Care: 2005,Vol 2,Issue 1)

    The established criterion on which to judge all laboratory tests used to help in the selection of cancer treatment is test 'accuracy' and not test 'efficacy'.

    Cell culture assay tests with cell-death endpoints have been exceedingly and reproducibly well established to be usefully 'accurate' in correlation with and predicting for clinical outcomes, including tumor response and patient survival.

    There should an expansion of Medicare and private insurance reimbursement to promote even greater utilization and development of laboratory-based mechanisms, like cell culture assays, for improving the match between tumors and an ever-increasing number of partially effective and very expensive drug therapies.