Tailoring The Therapy To The Cancer

[gpawelski]

Cell Culture Assays can help predict which chemotherapy drugs will work best in a cancer patient, by testing different drugs directly against a sample of the tumor to identify which is the most effective. Conventionally, chemotherapy drugs are prescribed based on their overall performance in past clinical trials. However, the best drugs identified may fail to help between 30% and 60% of patients, or more, depending on the disease and the individual. Not all patients will have the same response to the same chemotherapy.

When a cancer patient sees a medical oncologist, they are told that their cancer will be treated with "empiric" or "physician's choice" drugs. However, the average treatment for the average patient cannot possibly work all the time because there are no average cancer patients. Each patient's cancer is unique. Because of this, patients respond differently to the same anticancer drugs. Your treatment should be tailored to your cancer. Assay-testing can help your doctor appreciate how your cancer cells may respond to various anticancer treatments.

With assay-testing, a fresh, surgical specimen is obtained from a viable solid tumor. Less often, it is a malignant effusion, bone marrow, or peripheral blood specimen containing "tumor" cells. These cells are isolated and then cultured in the continuous presence or absence of drugs, most often for 3 to 7 days. At the end of the culture period, a measurement is made of cell injury, which correlates directly with cell death. There is evidence that the majority of available anticancer drugs may work through a mechanism of causing sufficient damage to trigger so-called programmed cell death or apoptosis.

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. In some cases, the tests can return results that show no treatment works. In that case, the patient may be advised to go to a clinical trial or forgo any further, fruitless therapy. Why harm a patient with very toxic and ineffective chemotherapy that would most likely not benefit them, and lower the quality of life that remains.

Some patients may not have easily-accessbile tumors (needle biopsies do not gather enough specimen), making it difficult to harvest a large-enough sample (200mg or 10mm in size). The tests are most reliable before a tumor has been exposed to chemotherapy. However, after a patient fails a previous chemotherapy treatment, the test still can be done once a patient waits at least four weeks.

It is true that what happens in the lab is not necessarily what happens in the patient. Cell death assays are not intended to be 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 is no different than any other medical test in this regard.

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.

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. The hallmark of cancer is its heterogeneity, yet the powers that be insist on trying to homogenize it, rather than tailoring treatment to the individual nature of the disease.

http://www.rational-t.com/

http://www.precisiontherapeutics.com/

http://weisenthalcancer.com/index.htm

[Lisa O]

I know of a few people who did this and found it to be helpful. Thanks for posting.

[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.