Thomas Jefferson University Hospital - Chemotherapy Resistance Testing Needs to Be Studied, Jefferson Surgeon Contends

Chemotherapy Resistance Testing Needs to Be Studied, Jefferson Surgeon Contends

Could be applied to tailoring therapy for patients with lung cancer

Thomas A d'Amato, MD, PhD

A study led by a thoracic surgeon at Jefferson Medical College (JMC) of Thomas Jefferson University in Philadelphia 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.

Reporting recently in the Journal of Thoracic and Cardiovascular Surgery, Thomas d'Amato, MD, PhD, Assistant Professor of Surgery at JMC, and his colleagues analyzed data on 4,571 non-small cell lung cancer tumor's 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 [analysis of a drug's components] that measures a specific patient's tumor resistance to a given cytotoxic drug," says Dr. d'Amato, whose clinical practice at Thomas Jefferson University Hospital is focused on general thoracic and foregut surgery with a primary emphasis in thoracic oncology. "This assay has the potential to guide therapy and can be used to tailor a patient's therapy by avoiding chemotherapeutic agents that will likely be ineffective."

Lung cancer is the leading cause of cancer death around the world. According to the American Cancer Society, an estimated 213,380 new cases of lung cancer (both small cell and non-small cell) will occur this year in the United States. About 160,390 people will die of this disease.

Applied successfully in other cancers
Chemoresistance (resistance of cells to the actions of specific chemicals) testing isn't new. Dr. d'Amato says that it has been applied successfully in ovarian and recurrent ovarian cancer and has helped many oncologists rule out chemotherapy agents because of toxicity and a low probability of clinical response. While the prevalence of drug resistance to common chemotherapy drugs in non-small cell lung cancer is alarmingly high, he says, the assay usefulness in tailoring appropriate therapies that help patients has yet to be proven.

"I believe the resistance assay is terribly underused," he says. "Having this assay available for a number of years, it is surprising that it has not been integrated into any clinical trials. In this age of targeted agents, it is time to avoid empiric therapy if possible, particularly in cancer. We don't cure many patients who have lung cancer with chemotherapy."

Dr. d'Amato's group also used the resistance assay to attempt to find markers – specific genes – that may be associated with resistance to chemotherapy, based on patient tumor resistance and individual gene expression profiles.

"In this era of empiric therapy, particularly with novel agents that are expensive, molecular testing needs to be paired to these studies," he says. "Clinical trial data is needed proving an agent's usefulness before clinical oncologists will use it."