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Chemotherapy Resistance Testing in Lung Cancer Patients Needs to Be Studied

Armen Hareyan's picture

A study led by a lung cancer surgeon at Jefferson Medical College suggests that oncologists should take more advantage of laboratory tests that have the potential to help determine a lung cancer patient's resistance to chemotherapy drugs. All too often, patients with non-small-cell lung cancer (NSCLC) are given standard chemotherapy drugs after surgery in a "hit or miss" fashion, without doctors knowing which drugs might have better chances than others to help treat the tumor. Steps should be taken to validate such resistance tests in clinical trials.

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Reporting recently in the Journal of Thoracic and Cardiovascular Surgery, Thomas d'Amato, M.D., Ph.D., assistant professor of surgery at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his colleagues analyzed data on 4,571 non-small cell lung cancer tumors' resistance to four pairs of chemotherapy agents, each of which included a standard platinum-based drug: carboplatin and paclitaxel (taxol), cisplatin and navelbine, cisplatin and docetaxel and cisplatin and gemcitabine.

Using the "extreme drug resistance" test to monitor cancer resistance in a test tube, they found resistance in 30 percent of tumors to carboplatin-paclitaxel, 24 percent to cisplatin-navelbine, 42 percent to cisplatin-gemcitabine and 27 percent to cisplatin-docetaxel.

"Clinical unresponsiveness for most patients with lung cancer to standard chemotherapy may be explained and measured accurately with an assay that measures a specific patient's tumor resistance to a given cytotoxic drug," Dr. d'Amato says. "This assay has the potential to guide therapy and can be used to tailor a patient



The "extreme drug resistance" test (EDR) is a soft agarose tritiated thymidine assay, which is a direct descendent of the original Salmon/Von Hoff Human Tumor Stem Cell or Clonogenic assay of the late '70s/early '80s. The assay is excellent at identifying drugs most likely not to work. All available cell-based assays (cell-death and cell-growth) 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. The goal of all cell-based 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. Some cell-based assays (cell-death) 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. Cell-death assays can 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. The EDR cell-growth assay is much less useful than are the various cell-death assays for the purpose of identifying effective treatment regimens. It doesn't mean that the information provided by the EDR assay is not helpful, it's that there are better ways of getting more useful information like higher evaluability rates, more drugs tested per specimens, multiple drug concentrations tested, and more extensive clinical validation of assay results. The cell-death assays are not growing anything. They are testing a drug or combinations of drugs (cytotoxic and/or targeted) with cells that are in their natural state (live/fresh), three dimensional tumor cell clusters. Clusters maintain natural cell-cell interactions. A personal treatment plan would be cheaper than the conventional (empiric) treatment protocol. Treating a patient with a drug or combinations of drugs that is most beneficial (sensitive), the first time around, eliminating most or all of the medication to manage side effects, and eliminating drugs that would be "resistant" to the cancer cells. This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free and overall survival. Literature Citation: Eur J Clin Invest 37 (suppl. 1):60, 2007 Thorac Surg Clin 17 (2007) 287–299. Gregory D. Pawelski