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Combination Therapy Shows Promising Results In Patients With Advanced Lung Cancer
Main Category: Lung Cancer News
30 May 2006 - An early phase study pairing an experimental targeted therapy with a common anti-inflammatory produced promising results in patients with advanced lung cancer, researchers at UCLA's Jonsson Cancer Center reported.
Pairing the targeted therapy Tarceva with the anti-inflammatory drug Celebrex increased response rates in lung cancer patients by about three-fold, said Dr. Karen Reckamp, an assistant professor of hematology/oncology and lead author of the study. The research appears in the June 1 issue of Clinical Cancer Research, the peer-reviewed journal of the American Association of Cancer Research.
Previous laboratory studies at UCLA showed that a cell signaling pathway known as COX-2 may be linked to resistance to drugs like Tarceva, which block tumor cell growth by targeting the protein EGFR, or epidermal growth factor receptor. Researchers theorized that giving Tarceva with Celebrex, a COX-2 inhibitor, would help battle resistance and prove to be an affective combination against lung cancer.
Typically, about 10 percent of lung cancer patients respond to Tarceva. In Reckamp's study of the combination therapy, about 33 percent of patients responded.
"Tarceva alone is a great drug and has a lot of clinical benefits, but for a small proportion of patients," Reckamp said. "With this drug combination, we saw an increase in response rates, indicating we are overcoming some resistance. We also may be beginning to understand the mechanisms of that resistance."
Volunteers in the Phase I study, patients with advanced lung cancer that had failed to respond to all conventional therapies, took several Celebrex pills and one Tarceva pill each day. After eight weeks, researchers looked at response rates. Patients were able to stay on the study as long as they didn't experience tumor growth. The longest duration of response was 93 weeks, Reckamp said, about three to four times longer than the average duration of response for a patient with advanced lung cancer.
The study was part of the Specialized Program of Research Excellence (SPORE) in lung cancer at UCLA's Jonsson Cancer, a program funded by the National Cancer Institute at top research institutions nationwide to find better and more effective ways to prevent, detect and treat lung cancer.
"This trial is an important early step in utilizing combination targeted therapies in lung cancer," said Dr. Steven Dubinett, director of UCLA's lung cancer SPORE and a professor of pulmonary and critical care medicine. "Dr. Reckamp's trial is the first to study increasing doses of a COX-2 inhibitor in lung cancer in an attempt to define an optimal biological dose. Larger trials of combination therapies utilizing this dose will now be required."
The biology of an individual's tumor determines whether they will respond to Tarceva. Because researchers don't yet fully understand what biologic characteristics determine response, they can't test patients first to determine who should be given the drug. Since 90 percent of patients don't respond to Tarceva, the drug was not an option for them. Reckamp said a portion of those may now be able to take Tarceva combined with Celebrex.
Because they target what is broken in a cancer cell and leave the healthy cells alone, therapies like Tarceva cause fewer side effects than conventional therapies such as chemotherapy, which targets all fast growing cells and often results in debilitating side effects. Reckamp characterized the side effects seen with the combination therapy as minor.
The next step is a larger Phase II study to confirm the efficacy of the combination therapy and further probe the mechanisms of Tarceva resistance, Reckamp said. That study is expected to begin at UCLA in the fall.
Reckamp's study was the first to determine the safest and most effective dose of Celebrex to use in lung cancer. Previously, doses were based on studies done in colon cancer patients.
"I think the results of this early phase study are promising and I anticipate we'll have a better understanding of Tarceva resistance in the near future," she said.
Lung cancer is the most common cause of cancer-related death in both men and women and accounts for about 29 percent of all cancer deaths. This year alone, 174,470 people will be diagnosed with lung cancer in the United States. Of those, 162,460 will die, according to the American Cancer Society.
Only about 15 percent of people who get lung cancer reach five-year survival. Those with advanced disease usually survive less than a year.
"It's crucial that we develop better treatments for this disease," Reckamp said.
Taconite a suspect in Iron Range cancer deaths
by Jessica Mador, Minnesota Public Radio
March 29, 2007 - After three dozen new cases of a rare form of lung cancer were reported among Minnesota Iron Miners, the state health department says it will launch studies to determine the cause. Mesothelioma is linked to asbestos exposure but some mine workers are concerned that taconite dust may also be a culprit.
These new cases bring the total to 52 on Minnesota's Iron Range. Health officials say that number is abnormally high for the population. The challenge is to identify the cause of the disease, a challenge complicated by the fact that it can be 40 or 50 years before mesothelioma symptoms present themselves.
The disease is traditionally associated with asbestos and no studies have proven that it can be caused by other airborne particles such as those released in taconite production.
Mary Manning, the director of health promotion and chronic disease at the Minnesota Department of Health, says these new cases make it imperative to rule out other possible sources of mesothelioma.
"People are dying from mesothelioma because it shows they've been exposed to asbestos and if there's any other cause, I think we need to is find out what that is and get the answers that people need." she said.
That is exactly what the first of the new Department of Health studies hopes to do. The project is a follow up to a 2003 study of Minnesota mine workers. It will research possible places where workers who now have mesothelioma may have been exposed either while working at the mine or in some other job during their lives. Officials hope the study will also answer questions about the possible dangers of taconite dust.
"Those fragments get into the air and there's been questions over the years about what the health effects associated with those mineral fragments are," she said.
John Linc Stine, director for environmental health at the Minnesota Department of Health, is studying the effects of breathing taconite dust on lab rats to determine a safe level for humans -- that is, how many fibers in how much air is a safe level of exposure. No such standard now exists. Stine says it's important to know what job each worker did when they contracted the disease.
"Whether it was related to mining activity or whether it was involving changing the brake linings on mine trucks where there could be other fibers generated. So it's really trying to look at what activities were conducted in their jobs and what parts of their jobs might have put them at risk for mesothelioma," Stine said.
Mine officials also want to know whether iron ore mining can be linked to mesothelioma. On the same day that the Department of Health announced its studies, Ohio-based Cleveland Cliffs announced it will do a study at its Northshore facility. Designed to work in conjunction with the state, Cleveland Cliffs will examine whether breathing taconite dust could be making its workers sick.
Mine spokesman Dana Byrne says it's in the company's best interest to find out whether mining causes mesothelioma.
"The whole idea is to come up with a study that's somewhat conclusive and hopefully puts the issue to rest once and for all," Byrne said.
The company is currently planning an expansion at its Northshore mine. Byrne says that's a major part of what motivated company officials to launch the health study. He says they don't believe the taconite dust is dangerous.
"To get beyond this issue we feel we have to do this study. Not have to do it, want to do it. So that we can move forward with some of the plans we have at Northshore. So it's a question we'd like to have answered as well as the public."
State Pollution Control Agency and health officials are helping to design the Cleveland Cliffs study, which will focus on current and past Babbitt and Silver Bay employees.
In Duluth, Jackie Paaso says she welcomes the studies. She lost her husband to mesothelioma. He worked for 30 years as a sheet metal worker, until he got sick. Paaso says the family always suspected Floyd's cancer was caused by his work.
"He used to make a paste out of asbestos, when he would cover different things with his sheet metal work. It's been hidden, I think," Paaso said.
Paaso says she wishes these studies would've been done earlier. It may have prevented other families from losing loved ones. Floyd Paaso died from mesothelioma in February 2006. "To sit and watch somebody going downhill was very very difficult," she said. "But we didn't live like it was the last day. We just kept living like we normally do or you wouldn't be able to do it."
The mesothelioma studies are expected to take up to three years and cost up to $1 million.