Chemosensitivity Testing

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Chemosensitivity Testing

by Gdpawel on Sun Jul 11, 2004 12:00 AM

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Presently used chemotherapy drugs have a high rate of failure. This was brought out in a January 10, 2002, issue of the New England Journal of Medicine, when it was noted that 20 years of clinical trials using chemotherapy on advanced lung cancer have yielded survival improvement of only 2 months. It also pointed out that 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%. In that case, knowing which chemotherapy agent "will" or "will not" work is essential. Chemosensitivity Testing 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. Another Name Cell Culture Drug Resistance Testing 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. 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. Ken Blackman, PhD. Solid Tumors Only. 1-800-262-6520 Anticancer, Inc., San Diego, CA. Robert Hoffman, PhD. Solid Tumors Only. 1-619-654-2555 Oncotech, Inc., Irvine, CA. John Fruehauf, MD. Solid Tumors and Hematologics. 1-714-474-9262 / FAX 1-714-474-8147 Sylvester Cancer Institute, Miami, FL. Bernd-Uwe Sevin, MD. Solid Tumors Only. (especially GYN). 1-305-547-6875 Human Tumor Cloning Laboratory, San Antonio, TX. Daniel D. Von Hoff, MD. Solid Tumors Only. 1-210-677-3827 Rational Therapeutics Institute, Long Beach, CA. Robert A. Nagourney, MD Solid Tumors and Hematologics. 562-989-6455 DiaTech Oncology, Brentwood, TN. Vladimir D. Kravtsov, MD, PhD Medical Director 1-615-294-9033 Weisenthal Cancer Group, Huntington Beach, CA. Larry M. Weisenthal, MD, PhD. Solid Tumors and Hematologics. 1-714-894-0011 / FAX 1-714-893-3659 / e-mail: mail@weisenthal.org One interesting note about Dr. Larry Weisenthal (Weisenthal Cancer Group), a male NSCLC (diagnosed stage IIIB or IV) patient availed himself to the Weisenthal Cancer Group for chemosensitivity testing. Tissue specimens that were sent to the lab showed resistance to single agent cisplatin and carboplatin and resistance to taxol. However, the drug combination of gemcitabine + carboplatin + vinorelbine + high dose tamoxifen + gefitinib (Iressa) was very synergistic and tested sensitive. He completed 6 x 3 week cycles incorporating 2 doses per cycle with the exception of carboplatin which was administered only once per cycle. After two cycles the main mass in his lung had reduced 85% and lymph nodes were virtually undetectable. After 4 cycles the CT of his lung showed only a small residual mass which was not detected by PET. He just had his first scan since completing the IV chemotherapy in October 2003 (he continues on Iressa at 250mg/day) and all appears unchanged and is still considered a complete response by his oncologist. Without the screen, he firmly believes he would have been placed on standard therapy (like taxol/carboplatin) which would not have been nearly as effective (if at all) and according to his oncologist, certainly would not have ever been treated with the combination that had shown activity in the screen. His oncologist at the leading cancer center appears to be a firm convert to the benefits of this prescreening.

RE: Chemosensitivity Testing

by survivor1dallas on Wed Dec 22, 2010 03:52 AM

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Dallas, Tx.  Dr. June Meymand 972-661-8140  chemosensitivity testing for Dallas patients.  Great test and doctor who interprets them for us lay people.  I am staying at the clinic now and it is amazing to see the other people helped and how the individual plans are developed. 

Best Wishes and Happy Holidays,  BT

RE: Chemosensitivity Testing

by greatdad on Thu Dec 23, 2010 02:27 PM

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Does anyone know where they do chemosensitivity testing in Canada?

RE: Chemosensitivity Testing

by Lizabeth1999 on Thu Dec 23, 2010 02:41 PM

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The downside to this is that the sensitivity testing may come up with results that are not in the approved protocol for your type of cancer.  For example, you have head and neck cancer and the test shows that you are senstive to chemo agents used for treating colorectal cancer.  And then there's the rub....

Without it being an approved treatment protocol for your type of cancer, the roadblocks begin.

Don't get me wrong.  We did this kind of testing and I thought it was hugely beneficial and extremely informative, and if it helps one person, one person at a time is enough.  Unfortunately, there is still so much push back from mainstream medicine and what's accepted and what is not.....it is just an uphill battle.  Not to mention that many oncologists will tell you that these tests have not been "validated" yet, so patients might not find doctors willing to collaborate.

Thanks for posting the information.  I think it's a huge step in the right direction and I am thankful we did the testing.

RE: Chemosensitivity Testing

by Gdpawel on Wed Feb 02, 2011 02:14 AM

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It has been very routine and well-accepted practice to prescribe drugs in cancer types and disease stages outside of those in which the drugs originally received FDA approval. Generally, insurance companies have paid for drugs used outside of FDA-approved settings because the treating physician finds their use in those instances to be "medically necessary." An estimated 60% of anti-cancer drugs are used off-label. Medicare has radically expanded its authorization for use of cancer drugs by putting off-label decision making in the hands of compendia writers. Reimbursable drugs include those prescribed off-label as long as they are listed in compendia officially designated by the Center for Medicare and Medicaid Services (CMS), Medicare's parent agency. Most private insurers follow Medicare's lead when setting their cancer drugs reimbursement policy. CMS gave oncologists the okay to use the NCCN compendium to justify payment for the off-label use of cancer drugs. In addition to the NCCN drug registry, CMS approved Elsevier's Clinical Pharmacology and Thomson Micromedex DrugDex compenium. My personal belief in having additional support of drug patient-specific activity, as determined by extensive laboratory pre-tests to improve patient outcomes, could very well bolster an argument for off-label use of specific cancer drugs. Also, by having additional support of drug patient-specific activity, as determined by extensive laboratory pre-tests (chemoresponse assays) to improve patient outcomes, could very well bolster an argument for off-label use of specific cancer drugs, with no economic ties to outside healthcare organizations, and recommendations made without financial or scientific prejudice. What is the precedent for using cell culture assays tests? There isn't one paper, or two, which by itself, makes a case for or against cell-based assays. Nor does the proposition that the whole thing depends on one study or even one review. You've got to consider the body of literature as a whole. The fact that none of this exists as one neat, convenient paper in the New England Journal of Medicine does not, in any way, negate the existence of this body of information. It has been found that newer methods of "cell-death" assays have an overall predictive accuracy of 98.2% concerning treatment response, which compares favorably with older, previously published data ranging from 75% to 92%. (Staib,P.et al. Br J Haematol 128 (6):783-781, March 2005) We have tests such as estrogen receptor, progesterone receptor, Her2/neu, BCR-ABL, C-KIT, CD-20, etc., and panels of immunohistochemical stains for subclassifying tumors. All of these tests are used to select chemotherapy in precisely the same manner as cell culture assay tests are used. Also, we have the use of additional medical tests, such as serial CT, MRI, and PET scans, performed for the purpose of monitoring the size of the tumor to determine if it is shrinking or growing with chemotherapy. The purpose of this testing is to determine if chemotherapy with specific drugs should be continued or changed to different drugs. These radiographic tests are also used as an aid in making clinical decisions about the choice of chemotherapy. So yes, there is precedent for using cell culture assays.

RE: Chemosensitivity Testing

by jeannemac452 on Wed Feb 02, 2011 04:00 AM

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My husband was diagnosed with stage 4 nsclc and was told to get paliative care from MSKCC.  A friend suggested the Weisenthal Cancer Center in Ca. (we live in NJ).  They came up with a regimen that treated my husband.  Unfortunately, he died but not from the cancer.  I have met a number of people who were told to go home and get their affairs in order from Sloane Kettering and then went to Weisenthal.  One particular woman, who I still remain very good friends, is now alive 23 years later.  Another young man 30 ish was suffering from pancreatic cancer.  He, too, was told to get his affairs in order.  His protocol was not one that was used in the treatment of pancreatic cancer but it worked for him.  I met him a few years after his treatment and he was doing wonderfully.  I cannot understand why the mainstream medical profession is not following this new form of treatment.  I can only guess it has something to do with $$$$.

RE: Chemosensitivity Testing

by Gdpawel on Mon Mar 07, 2011 11:27 PM

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I know, up until recently, CTCA used drug resistance testing. This kind of testing measured only the drug "resistance" endpoints of drug testing. There are other pre-testing techniques that measure drug resistance and drug sensitivity for anti-tumor and anti-angiogenic activity. The current clinical applications of in vitro chemosensitivity/resistance testing is ever more important with the influx of new "targeted" therapies. I am a strong advocate of pre-testing for chemotherapy drug selection, and CTCA using "half the science" is better than using no science at all. However, Oncotech went out of business because Exqon threw them to the wolves. I wonder what they are doing now? It amazes me that private insurance carriers don't like to pay for these assays but should emphatically mandate it as a requirement for obtaining chemotherapy reimbursement against ill-directed treatments. Evidence and costs both support the use of these tests and is more than sufficient to justify them. What is the precedent for using cell culture assay tests? We have tests such as estrogen receptor, progesterone receptor, Her2/neu, BCR-ABL, C-KIT, CD-20, etc., and panels of immunohistochemical stains for subclassifying tumors. All of these tests are used to select chemotherapy in precisely the same manner as cell culture assay tests are used. Also, we have the use of additional medical tests, such as serial CT, MRI, and PET scans, performed for the purpose of monitoring the size of the tumor to determine if it is shrinking or growing with chemotherapy. The purpose of this testing is to determine if chemotherapy with specific drugs should be continued or changed to different drugs. These radiographic tests are also used as an aid in making clinical decisions about the choice of chemotherapy. So yes, there is precedent for using cell culture assays.

RE: Chemosensitivity Testing

by ynouhi on Fri Mar 25, 2011 08:05 PM

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Check out DiaTech Oncology in Montreal, the MiCK assay is a chemotherapy drug sensitivity microculture assay.

 

Good luck

RE: Chemosensitivity Testing (MiCK Assay)

by Gdpawel on Sun Jul 31, 2011 02:58 AM

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While apoptosis represents an important mechanism of programmed cell death, it is only one of several cell death pathways. Apoptotic cell death occurs with certain mutational events, DNA damage, oxidative stress and withdrawal of some growth factors particularly within the immune system. Non-apoptotic programmed cell death includes: programmed necrosis, para-apoptosis, autophagic cell death, nutrient withdrawal, and subtypes associated with mis-folded protein response, and PARP mediated cell death. While apoptotic cell death follows a recognized cascade of caspase mediated enzymatic events, non-apoptotic cell death occurs in the absence of caspase activation. While caspase activation (MiCK Assay) is of interest, comparably easy to measure and useful in many leukemias and lymphomas, it does not represent cancer cell death in all circumstances and can be an unreliable parameter in many solid tumors. Responding to functional profiling's scientifically sound suggestion that caspase activation is but one mode of cell death that may be more applicable to hematologic than all solid tumors, the MiCK Assay is a clear indication that they are following the literature of cell-based functional profiling. Labs that focus on measurements of caspase activation can only measure apoptotic cell death. While apoptotic cell death is of importance in hematologic cancers and some solid tumors, it does not represent the mechanism of cell death in all tumors. This is why functional profiling measures all cell death events by characterizing metabolic viability at the level of cell membrane integrity, ATP content, or mitochondrial function.

RE: Chemosensitivity Testing

by jenmas on Tue Jan 24, 2012 06:11 PM

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On Dec 23, 2010 2:27 PM greatdad wrote:

Does anyone know where they do chemosensitivity testing in Canada?

Hi - did you ever receive a reply on chemo tesing in Canada?  I've been looking for someone here also and cannot find anyone.  Thanks for your help!  Jen

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