Personalized medicine enables physicians to provide tumor-specific chemotherapy

By Jeni Baker

The number one cancer killer of American men and women, lung cancer is a serious and frightening disease.

This is due in part to the insidious nature of the disease, which can progress quickly and often is not diagnosed until it has reached an advanced stage.

It is also because oncologists haven’t had much tumor-specific information to guide their treatment decisions -- meaning that patients often must suffer through ineffective treatments -- and the side effects of those treatments -- in an effort to find one that works.

But this trial-and-error approach could soon be a thing of the past.

Duke University is conducting first-of-its-kind research that may offer patients with advanced non-small-cell lung cancer unprecedented hope for more effective treatment. The clinical trial uses genomic analysis to guide the choice of initial chemotherapy treatment.

“There are different treatment options for any disease state, and choosing the most appropriate treatment can be a guessing game,” says the study’s primary investigator, Duke oncologist Jennifer Garst, MD. “Selecting the best one early in treatment offers the best chance for our patients, and that’s what this study is about.”

All Lung Tumors Are Not Created Equally

While people may know that there are different types of lung cancer -- small cell, non-small cell and squamous cell, for example -- many don’t realize that there are also different types of lung cancer tumors. That’s because everyone has a unique genetic makeup -- and that makeup influences both normal cells and cancerous ones. In other words, lung cancer tumors are as individual as the people who have them.

Herein lies the key to revolutionary new technology.

Duke scientists have developed tests that can identify the precise genetic pathways -- the patterns and activities of thousands of genes -- that cause normal cells to become cancerous. These “genomic signatures” are enabling physicians to treat cancer patients with existing chemotherapy drug(s) that specifically target the unique defective pathway that led to their disease at a molecular level.

This type of targeted therapy means that less time is wasted pursuing chemotherapies that may be appropriate for one patient, but not for another -- getting effective treatments to patients sooner, when they’re most likely to help. It also means that patients are spared the side effects of treatments that won’t work for their particular tumors.

But how do physicians obtain the genomic profile of a lung cancer tumor?

After a patient has enrolled in a clinical research trial, a tissue sample is obtained from the tumor and immediately frozen to -70 degrees in a procedure known as a fresh-frozen biopsy. This sample may be obtained in several ways, depending upon the patient and his or her disease state, including via CT-guided biopsy, bronchoscopy, lymph node biopsy, or surgery.

After analyzing a tumor’s genetic material, scientists can determine which drugs the tumor does and does not respond to on a cellular level, enabling them to prescribe the correct chemotherapy for the patient’s unique cancer type.

“Chemotherapy will probably continue to be the foundation of many cancer treatment strategies for years to come,” says Anil Potti, MD, the lead author of many of Duke’s genome-lung cancer studies and an assistant professor of medicine in the Duke Institute for Genome Sciences & Policy.

“We believe these new tests will enable physicians to personalize chemotherapy so that it increases tumor response rates and improves outcomes for lung cancer patients.”

Clinical Trial Appears Promising

After being diagnosed with Stage 4 non-small-cell lung cancer in April 2007, Artis Perry, 64, opted to be the first patient to enroll in Garst’s study, the first-ever genomics-guided lung cancer treatment protocol, currently under way at Duke.

Because a genomic analysis determined that Perry’s tumor was resistant to cisplatin, a commonly used front-line chemotherapy drug, he was assigned to a chemotherapy treatment group that did not involve cisplatin -- and was instead initially treated with a combination of the non-platinum drugs pemetrexed and gemcitabine.

Six months later, things are going well for Perry. He and his doctors believe that the chemotherapy drugs used were the most appropriate initial treatment for the unique genomic makeup of his tumor -- and that Perry’s participation in the clinical trial may have improved his chances for a long remission.

“Mr. Perry completed the full six-cycle treatment course of the genomics clinical trial and has had a dramatic response to therapy,” says Garst, his oncologist. “The size of his tumor has shrunk by more than 50 percent.”

Cyndee Sessoms, 49, also a patient of Garst, received a Stage 4 non-small-cell lung cancer diagnosis in May 2007. She, too, chose to enroll in the genomics-guided lung cancer treatment study. Unlike Perry, however, genomic analysis of her tumor revealed it to be sensitive to cisplatin, which dictated her assignment to a different arm of the study than the one Perry was assigned to.

“The first time I met Ms. Sessoms, she was in a wheelchair, suffering from a lot of pain, and having difficulty breathing,” says Garst. “Within two treatment cycles, she had improved dramatically and no longer required oxygen. Now, after having completed all six cycles of the treatment protocol, she’s running two miles a day and taking care of her nine-year-old daughter.”

Genomic technology “gives us the ability to customize therapy for each individual patient and offer them the best chance of remission and shrinkage of their tumors with the first treatment we give them,” Garst says. “The goal is to optimize patients’ chances of responding to treatment, while minimizing the side effects they must endure.”

Duke Medicine is making other important strides in lung cancer, as well. For example, Duke scientists have developed the first genomic test (the Lung Metagene Predictor, or LMP) to predict which patients with early-stage lung cancer are at high risk of recurrence -- and require chemotherapy to live -- and which can forego the toxic treatment and its side effects. A clinical trial using the LMP model is currently in development.

For more information about any clinical trial at Duke, ask your physician to call the Duke Consultation and Referral Center toll-free at 888-ASK-DUKE (275-3853).