NASHVILLE, TN (Ivanhoe Newswire) - It's the number one cancer killer in America. We all know smoking causes it, but if you've never had a cigarette, a mutation in your genes could lead to lung cancer. Now, doctors are attacking genes, shrinking tumors and giving patients hope.
"I had a dry cough that I could never get rid of," Michael McDill told Ivanhoe. "You have a life, you have a family and you don't expect that at all at that age."
Michael McDill was just 36 years old when he got life-changing news.
"They said stage 4 lung cancer," Michael said.
The model airplane collector never smoked a day in his life, but, a specific genetic mutation called Anaplastic lymphoma kinase or ALK, caused a cancerous tumor to grow. The gene is found in forms of lung cancer affecting thousands of non-smokers. Doctors attacked it with 10 rounds of chemo and heavy radiation. The treatments didn't work, but a clinical trial gave Michael hope.
"We are testing 10 different genes with 38 different mutations," Leora Horn, M.D., MSc, FRCPC, an assistant professor of medicine and clinical director of the thoracic oncology program at Vanderbilt University, said.
Doctors pinpoint specific gene mutations and select a drug designed specifically for carriers of that mutation.
"The goal is to be able to find an agent that can block it and prevent the growth of that cancer," Dr. Horn said.
In Michael's case, Doctor Horn believes the answer is in the newly FDA approved drug Crizotinib.
"It's targeting the tumor and blocking signaling in the tumor and when you block the signaling in the tumor is like you're cutting off a wire," Dr. Horn explained.
In an early clinical trial, more than 57 percent of patients saw their tumors shrink after two months on the drug.
"In 60 percent of patients, they will have more than 30 percent of shrinkage of their tumor," Dr. Horn said.
She also said the therapy is still fairly new and larger trials are underway to test the drug's efficacy. As for Michael, after a year on the drug his scans show no traces of the disease. While the drug won't cure him, it's helping him control his cancer and maintain his quality of life and he's enjoying every minute of it.
"Live, laugh, love," Michael said.
Lung cancer is just the beginning. Doctors are now using the same approach to test genes in melanoma, breast cancer and colon cancer.
Like many targeted therapies, Crizotinib is not cheap. The drug, which has only been approved for use in the U.S., costs almost $10,000 per month.
The most common side effects of the drug are nausea, diarrhea, and minor vision problems.
BACKGROUND: Lung cancer is the deadliest type of cancer for both men and women. Each year, more people die of lung cancer than of breast, colon, and prostate cancers combined. In the US, approximately 220,000 people are diagnosed with lung cancer each year. Lung cancer deaths result in 27% of all cancer deaths in U.S. (Source: www.nationallungcancerpartnership.org)
CAUSES: Cigarette smoking is the leading cause of lung cancer, the more cigarettes a person smokes per day the greater the risk of lung cancer. Inhaling second hand smoke is also responsible for causing lung cancer, resulting in approximately 3,000 lung cancer deaths in the U.S each year. (Source: www.ncbi.nlm.nih.gov)
SURPRISING FACTS: Even though it's less common, some people who don't smoke get lung cancer too. Every year, 16,000 to 24,000 Americans die of lung cancer even though they have never smoked. If lung cancer in "never smokers" (defined by researchers as people who have smoked fewer than 100 cigarettes in their lifetime) had its own category separate from lung cancer in smokers, it would rank among the top 10 fatal cancers in the United States. ( Source: American Cancer Society)
IT'S IN YOUR GENES TOO! The EML4-ALK fusion gene is responsible for approximately 3-5% of non-small-cell lung cancer(NSCLC). The vast majority of cases are adenocarcinomas. On average, ALK lung cancers are found in people who are approximately 10-15 years younger than other lung cancer patients, and who are also significantly more likely to be non-smokers and somewhat more likely to be light former smokers.
NEW THERAPY: Traditional treatments for lung cancer can involve surgical removal of the cancer, chemotherapy, or radiation therapy. The newly FDA approved drug Crizotinib is curing cancer and changing lives. Crizotinib is approved for the treatment of patients with locally advanced or metastatic non-small cell lung cancer. Approximately 85% of lung cancers are non-small cell lung cancer so researchers are hopeful that Crizontinib may be the miracle pill for many patients. In a clinical trial with Crizotinib almost 60% of patients saw their tumors shrink after only two months while using the drug. Other studies show that Crozotinib may also be able to cure other forms of cancer as well. (Source: www.cancer.gov)
Dr. Leora Horn, Assistant Professor of Medicine & Clinical Director of Thoracic Oncology Program Specializing in Thoracic Oncology at Vanderbilt Medical Center talks about personalized medicine in the treatment of lung cancer.
Can you tell me a little about genetics and lung cancer? You provide what's called personalized medicine and you're using genes to find out about cancer – how are we using genes these days for personalized medicine?
Dr. Leora Horn: The Personalized Cancer Medicine Initiative at Vanderbilt-Ingram Cancer Center has been available since 2010. We perform molecular profiling on all of our non-small cell lung cancer patients and right now we're testing 10 genes for 38 different mutations. Currently, there are FDA-approved therapies for patients with epidermal growth factor receptor (EGFR) mutations and the ALK rearrangement and our hope is that with future discoveries and clinical trials we will have targeted therapies available for other known mutations in lung cancer.
Would you explain about the ALK gene?
Dr. Leora Horn: ALK stands for Anaplastic Lymphoma Kinase and ALK was discovered in 2007 in Japan. This is basically a specific mutation in a patient's tumor that drives tumor growth and the goal of personalized medicine is to find an agent that can block ALK and prevent the growth of that cancer.
How does it work in the body?
Dr. Leora Horn: When you take the drug crizotinib it is blocking signaling within the tumor and when you block the signaling it is much like cutting off a wire and preventing that tumor from growing further. What we're seeing with our patients is that this blocking action is actually causing the tumor to shrink.
It's causing the tumor to shrink completely?
Dr. Leora Horn: Not completely. About 60 percent of patients will have more than 30 percent shrinkage of their tumor, so it doesn't go away completely. For a small percentage of patients, the tumor does seem to disappear to where you cannot see it on a CT scan, but on average it will shrink 30 percent or more.
How can it prolong their life and make it better?
Dr. Leora Horn: Right now the studies are measuring progression free survival with patients being alive without progression of their cancer for about nine months. However, we're seeing many patients with a longer time to disease progression and in some patients we are seeing shorter progression. We're also seeing that the drug is well tolerated with very minimal side effects, including some visual side effects, maybe a little bit of nausea or some gastrointestinal upset, but the drug is very well tolerated on the whole.
So this is a clinical trial?
Dr. Leora Horn: Phase 2 and 3 clinical trials for patients in the U.S. who have previously received chemotherapy are now closed because crizotinib was approved by the FDA but the trials are still open worldwide where crizotinib is not available commercially. There is one Phase 3 clinical trial still open in the U.S. that is for patients who are newly diagnosed with lung cancer and have never received systemic treatment. They must have the ALK rearrangement and they're going to be randomized to receive either chemotherapy or crizotinib. So that's the one trial that's still open in the U.S. but the other trials closed shortly after the drug received FDA approval.
So the drug did get FDA approval during the clinical trial?
Dr. Leora Horn: The drug got approval based on the results that have been seen in the Phase 1 clinical trial and so right now patients don't have to go on study in the U.S. to get crizotinib. The first line study is still open here and we will enroll eligible patients. We still have some patients that were getting that drug on study in the Phase 2 and 3 clinical trials, so if they were on study already they are staying on study right now.
How do you get these genes that are in your body? We're talking about Michael and he doesn't have a history of lung cancer in his family so how is it possible that he has this gene?
Dr. Leora Horn: That's something that we don't know and hopefully in the future we'll know more. There are about 220,000 people in the U.S. who are diagnosed with lung cancer every year and about 15 percent of those patients are never smokers, so they're similar to Michael. The ALK rearrangement appears to occur more commonly in never smokers or former light smokers so these are people who don't have much of a smoking history. We don't know why Michael has the ALK rearrangement and we don't necessarily know if his children or his siblings are at risk for having ALK positive cancer in the future. There are other mutations such as EGFR where we have seen what we call a germline mutation which means that it is in the patient's DNA and these patients have siblings or other family members who will have a germline EGFR mutation. ALK is so new that we don't know as much about it and whether germline mutations exist.
What does ALK stand for again? It's a nice name for a gene…
Dr. Leora Horn: ALK stands for Anaplastic Lymphoma Kinase
There are personalized therapies. Can you tell me about Michael's therapy?
Dr. Leora Horn: Michael had several rounds of chemotherapy before he came to us and because he was a never smoker we recommended he get tested for the ALK rearrangement and his tumor came back as positive for ALK. ALK is an interesting story about designing the right drug for the right population. If you had taken this drug and just given it to all lung cancer patients, we wouldn't have seen the incredible response rates that we've been seeing. But because this study and the way it was designed mandated that only patients who have ALK positive lung cancer receive the drug, we are seeing very dramatic responses. It was the right drug given to the right people and that's why we're seeing the right responses.
Do you think that this could replace other drugs one day?
Dr. Leora Horn: I don't think it will necessarily replace chemotherapy drugs but it may give us some information about other molecular targets for which we can develop drugs. Right now, when ALK positive patients develop resistance to the drug and their tumor starts growing again we are doing new tumor biopsies and we're actually sequencing the tumor DNA to figure out why the drug stopped working. Based on that information, we hope we can figure out what drug or drug combination we should give them next.
In Michael's case, he takes a pill twice a day. What difference have you seen in him, so far?
Dr. Leora Horn: Twice a day, once in the morning and once in the evening. Michael is young and he had a lot more reserves than some other patients so he was still working and doing most of his usual activities when we started seeing him. When he first came in he had a cough but after a few weeks of therapy his cough went away. On his CT scans we initially saw a little bit of shrinkage of his tumors. I think it's close to a year now and we can't actually see any tumor on his CT scans.
What's next for him?
Dr. Leora Horn: Well, we hope he has a long durable response to therapy but what comes next is to figure out which drug to use when the crizotinib stops working.
You have personalized medicines for more genes?
Dr. Leora Horn: Right now, we're testing 10 genes for 38 different mutations and that's specific to lung cancer. Here at Vanderbilt-Ingram we're doing similar things for different genes in melanoma, breast cancer and colon cancer. What personalized medicine really means is that we're figuring out if a patient has a mutation and if they do we're giving the patient a drug that targets that mutation, either through a clinical trial or if the drug is approved they may get it that way. We hope that by matching the right drug to the right patient we can hold their cancer at bay and improve their quality of life and their survival.
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