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Targeting lung-cancer therapy

By bringing new clinical trials to the Alliance, Renato Martins seeks to improve outcomes for patients with advanced lung cancer
Dr. Renato Martins and oncology fellow Dr. Laurie Carr
Alliance lung-cancer specialist Dr. Renato Martins and oncology fellow Dr. Laurie Carr examine lung X-rays. Martins is working to foster new collaborations with lab investigators who study lung-cancer development and progression. Photo by Todd McNaught

Many patients speak of the fear, shock and disbelief they experience when they first learn they have cancer. But when the disease strikes the lungs, the overwhelming feeling is often guilt.

With about 90 percent of lung-cancer cases attributable to smoking, many patients feel as though they have brought the disease on themselves, said Dr. Renato Martins, a lung-cancer specialist who is bringing new clinical trials for the disease to the Seattle Cancer Care Alliance. It's a complication he tries hard to alleviate during his first consultation with a patient who learns that he or she has the disease, the nation's number one cause of cancer-related death.

"It's common for the patient to feel that it's their fault for getting lung cancer," said Martins, assistant professor of medicine at the University of Washington and medical director of thoracic and head and neck oncology at the Alliance. "But cigarettes are addictive, and the majority of smokers begin smoking in early adolescence, when individuals can't really be held responsible for their actions."

With overall survival rates for lung cancer about 15 percent, Martins' first priority is to help patients focus on their treatment, which may include surgery, chemotherapy or a combination of the two. Since his arrival in February, he has set his sights on improving those outcomes by expanding the number of clinical trials available to Alliance patients and by fostering new collaborations with laboratory investigators who study lung-cancer development and progression.

In addition to lung-cancer patients, Martins and a team of surgeons, radiotherapists and other specialists treat patients with cancers that strike the head and neck. About 300 patients received care at the Alliance for all of these diseases during the past year.

By seeking out new lung-cancer research opportunities for the Alliance, Martins hopes to make available new treatments for his patients.

"We are very close to opening our first large international clinical trial here," he said. The study, which is expected to begin enrolling patients within the next several months, will compare the effectiveness two different chemotherapy regimens in patients with advanced lung cancer.

Two other lung-cancer trials expected to begin within the next year will evaluate new drugs and techniques that could make it easier for doctors to prescribe the most effective initial course of therapy for each patient's unique disease characteristics. Since most lung-cancer cases are diagnosed when the disease is advanced and requires immediate intervention, patients will greatly benefit from this knowledge, Martins said.

"Tumors from two different patients can look the same under the microscope, yet the patients will respond very differently to the same treatment," he said.

For example, of the approximately one-third of patients who are candidates for surgery, about one-third will achieve long-term cure.

"What we don't know now is what is different about the molecular biology of those tumors that do respond to surgery," he said "We'd like to be able to predict how a patient will respond before we operate or before we administer a particular type of chemotherapy. We'd also like to be able to determine quickly whether a drug is working so that we can adjust a patient's therapy if necessary."

One of the proposed new trials, which will employ a method known as positron emission tomography (PET) scans, could enable doctors to rapidly determine whether a patient's tumor is responding to drug therapy. PET scans allow doctors to visualize a tumor based on its metabolic activity. Before the procedure, patients are given an intravenous infusion of a radioactive tracer. Tissues that are actively growing and dividing take up the tracer, which makes them visible to the scanner. A tumor that is responding to chemotherapy would show less metabolic activity than an untreated tumor or one that responds poorly to the drug. Because PET scanning is so sensitive, doctors can visualize a patient's response much more quickly after treatment has begun than is possible using other imaging techniques such as X-rays. If a tumor is not responding, new therapy can be administered before the cancer spreads.

Predicting patient response

A second trial, to be conducted in collaboration with Dr. Thomas Lynch at Massachusetts General Hospital, will focus on an exciting new drug called Iressa. The drug received approval last year from the U.S. Food and Drug Administration to treat non-small-cell lung cancer, the most common form of the disease. In a recent study, researchers found that in about 10 percent of patients treated with Iressa, tumors dramatically shrank soon after therapy was initiated. Lynch's team discovered that patients who responded favorably to Iressa carry a mutation in a gene that produces a protein called epidermal growth-factor receptor, which is found on the surface of cancer cells.

"We'd like to be able to prescribe Iressa as a first-line therapy for patients who are likely to respond," Martins said. "We'll determine that by analyzing DNA from patients enrolled in the trial to determine whether they carry the mutation. This is a first step in bringing us closer to how cancer care should be — that we treat a patient according the molecular biology of his or her tumor."

Other new drugs that hone in on specific subtypes of cancer may emerge as researchers begin to identify molecules that are released into the blood of lung-cancer patients. Such molecules, known as biomarkers, can provide clues to the unique biology of different forms of cancer and may serve as potential drug targets or help doctors monitor and predict outcome. Martins and members of his patient-care team hope to participate in these efforts by providing blood and tumor specimens from lung-cancer patients who consent to taking part in the research.

With the clear link between cigarette smoking and lung cancer, the most effective defense against the disease is obvious, Martins said.

"The best public-health effort would be to get people to quit smoking, and even people with cancer can benefit from quitting," he said. "Yet there are still former smokers who quit many years ago who will develop lung cancer and who will die from the disease. We must continue our efforts to develop more effective treatments for them."

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