Positive Health Online

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 tumour 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.

Assay-testing is based on a biological principle that when a drug is effective, it will induce cell-death (apoptosis) in the cancer cell (this is the new technology). If the cancer cell is resistant to a drug, apoptosis will not occur. Assay-testing for apoptosis will determine whether a drug kills the tumour. Chemosensitivity testing (assay-testing) can take the guesswork out of cancer treatment. Currently, physicians select a drug and must wait about six months to see whether it is effective on a particular patient.

These cell-culture assay-tests provide much more powerful prognostic information. They tell you that a given form of treatment has an above-average probability of being associated with a clinical response and/or with being associated with above-average survival. Likewise, they indicate that given treatment is associated with a below average probability of response and/or survival.

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 tumour 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 tumour 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 tumour 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.

Laboratory Tests Assays

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 Tumour 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 tumour 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 tumour reacts to strongly than one your tumour 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.

Progress Among Medical Professionals

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. It seems probable that a self-educated oncologist, genuinely on the cutting-edge would tend to be aggressive in actual treatment beyond mere rhetoric and make use of running tests on the biopsy before selecting a chemotherapy option.

Dr Ian Cree, Director, Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth UK performed the very first prospective, randomized clinical trial of physician's choice chemotherapy versus ATP assay-directed chemotherapy in non-surgically debulked, platinum-resistant ovarian cancer and presented it at the May, 2005 American Society of Clinical Oncologists (ASCO) meeting in Orlando, Florida.

The results were highly suggestive of an effect due to the assay, and the most successful drug regimens used were nearly all developed using the assay. UK results in cancer are always lower than in the US for a variety of reasons. Part of this is probably lead time bias, but data on surgical debulking may be part of the explanation. Patients in the US get a whole lot more surgery along the way than in Europe.

According to Dr Ian A. Cree, "… 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."

In 1983, medical publications introduced assays based on 'cell-death' (not cell-growth). This was a good five years before understanding the concept of apoptosis (apoptosis is a genetically programmed cell death pathway which exists in all cells, which is supposed to cause them to commit suicide if they become functionally deranged, but doesn't function properly in cancer cells, allowing them to grow abnormally without committing suicide, which can be triggered to occur by effective anti-cancer drugs).

Because clinical oncologists did not understand apoptosis then, these pioneering publications with 'cell-death' (instead of cell growth) endpoints were ignored, and neither clinical trials nor the application of cell death drug resistance assays were supported by academic and private practice clinical oncologists. The clinical utility and clinical accuracy of cell culture drug resistance testing with cell-death endpoints has now been proven.

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. After all, cutting-edge techniques can often provide superior results over tried-and-true methods that have been around for many years.

In the US, the Gynecologic Oncology Group (GOG) has decided to move forward with a study in platinum-resistant ovarian cancer, utilizing a different assay called EDR, to direct chemotherapy. However, this assay is specifically designed to identify 'inactive' rather than 'active' drugs. In this light, the EDR assay has the advantage of telling you who will 'not respond' but cannot in any way change the negative outcome by selecting an 'active' alternative. At least here in the US, it's a start!

There are other medical oncologists in the US, headed up by Drs Larry Weisenthal and Robert Nagourney, that are making proposals for a separate study, a front-line randomized trial with head to head comparison of several assays (EDR, ATP, DISC, MTT, as well as Caspase 3/7). These assays correlate very well with each other on direct comparisons of different methods. Different methods of assay results should be applied in choosing a particular drug regimen to be used in treating an individual patient's cancer.

References

Listing of Specialized Laboratories in the United States and Europe are available from the author.
Various Bio-Assay Journals are available from the Author