gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 125
Location: Pennsylvania
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 Posted: Sat Jul 09, 2005 12:16 pm Post subject: Treatment Tailored To Your Cancer |
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Drug Sensitivity and Resistance Assays or Chemosensitivity and Resistance Assays (CSRAs) 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.
The Americain Society of Clinical Oncology (ASCO) suggested in their technology assessment of CSRAs that the study of them should be a top priority. They did not however, recommend its use outside of a clinical study. This recommendation was a result of evaluating a less reliable form of assay-testing. There are two types of CSRAs, one that determines whether a drug stops a cancer from growing (cell-growth) and one that determines whether a drug kills (cell-death) the cancer outright. The ASCO report looked at the cell-growth tests, and not at the cell-death tests, that are a better predictor of whether a drug will work.
The ASCO panel says the cell-death tests weren't included in the review because, to them, there weren't any reliable studies assessing them. Even with the cell-growth analysis, many studies cited in the ASCO report showed twice as many patients who were given assay-directed therapy responded to treatment, compared to patients who were given "empiric-directed" therapies. The researchers claimed that the studies didn't show that using the tests helped people live longer than those prescribed a "standard" treatment. However, they cannot claim that "standard" treatments help people live longer than those that use "assay-directed" treatments.
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.
Resources: Various Bio-Assay Journals |
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