The Oncotech EDR Assay (PDF Download)

Oncotech's EDR Assay was developed for testing in vitro drug responses in solid tumors, and is the only solid tumor assay capable of identifying extreme drug resistance with over 99% accuracy. Validation of Oncotech's EDR assay technology has been documented by 450 clinical correlations obtained over an eight year period. Results of this study were published in the Journal of the National Cancer Institute¹. To date, Oncotech has performed EDR testing on over 80,000 tumor specimens for over 1,000 hospitals nationwide.

Results from the EDR Assay are used to determine the probability of non-response (extreme drug resistance) by the tumor to the selected chemotherapeutic agent. To accomplish this, our laboratory uses thymidine incorporation to calculate the proliferation of tumor cells after they have been plated in a 3D agarose media and exposed to a variety of chemotherapy agents.

Clinical Significance of the EDR Assay

In general, most solid tumors such as lung, ovarian and breast cancer may be treated with different combinations of chemotherapeutic agents. In the EDR Assay, panels of drugs specific for each tumor type are tested. When EDR is present, it is usually possible to eliminate the resistant drug(s) and still formulate a standard treatment regimen. Thus, the greatest utility of Oncotech's EDR Assay is found in those tumor types where more than one standard chemotherapy option exists.

Oncotech provides concise, easy to interpret reports that accurately identify ineffective agents. This approach provides a cost-effective means to manage cancer therapy, and saves unnecessary treatment related morbidity for the patient.

Chemoresistance vs. Chemosensitivity

Oncotech's unique Extreme Drug Resistance (EDR) assays should not be confused with traditional (clonogenic) chemosensitivity assays.

Chemoresistance

Chemoresistance and chemosensitivity are different. Chemosensitivity testing is performed to help the physician select an active chemotherapy agent. Drug resistance testing, such as Oncotech's Extreme Drug Resistance (EDR) Assay, is performed to identify ineffective agents, thus helping to prevent unnecessary patient exposure to toxic agents.

The distinguishing feature of Oncotech's EDR assay is the prediction of clinical failure with 99% accuracy.

The success of this assay results from extended exposure of the patient tumor cells to levels of chemotherapy agents which approximate the peak plasma levels attained after conventional IV administration. If a patient's cells proliferate after extended exposure to peak plasma levels of chemotherapy agents, then it can be accurately predicted that these cells will also demonstrate resistance to normal exposures in vivo.

Thus, Oncotech's resistance testing accurately identifies chemotherapeutic agents that will not be clinically effective. In terms of patient outcome, results from resistance testing help avoid unnecessary patient exposure to toxic agents.

Chemosensitivity

Chemosensitivity assays were modeled after bacterial culture and sensitivity (C&S) tests. Typically, there are many effective antibiotics on the market which can be used to treat bacterial infections. However, in treating cancer the list of effective treatment options typically is much smaller.

In general, the accuracy to predict chemosensitivity is only about 60-70%, whereas, the accuracy of prediction for drug resistance is greater than 99%. An application of Bayes theorem provides an explanation for the differences noted in accuracy between these two very different types of tests.

According to Bayes theorem, the predictive accuracy of any laboratory test is a function both of the characteristics of the technology (sensitivity and specificity) and of the biology of the disease to which the test is applied. Thus, where chemosensitive disease is significantly less frequent than chemoresistant disease, Bayes theorem predicts that chemosensitivity will be more difficult to accurately predict than drug resistance.

Other factors which complicate the accuracy of predicting chemosensitivity in the laboratory include:

• In poorly perfused tumors and tumor sanctuaries, drug delivery is decreased.
• If the host's liver has an altered metabolism, a decreased activation of prodrugs such as Cytoxan may result.
• Life-threatening toxicities can result because of individual normal tissue sensitivities, requiring that the drug dosage be cut back.
• Local areas of hypoxia or acidosis may inactivate certain drugs.
• Host-dependent resistance mechanisms can cause high false-positive predictions of in vitro chemosensitivity.
• Cytoxan, Ifosfamide and Hexamethylmelamine are by themselves inactive in vitro. Oncotech uses the active metabolites of these drugs in order to obtain accurate and reliable assay results.

¹Kern and Weisenthal. Highly Specific Prediction of Antineoplastic Drug Resistance with an In Vitro Assay using Suprapharmacologic Drug Exposures.
JNCI, 1990, 82(7):582-588.