Posts Tagged ‘story’

Novel immunotherapy vaccine decreases recurrence in HER2 positive breast cancer patients

One of only a few vaccines of its kind in development, GP2 has been shown to be safe and effective for breast cancer patients, reducing recurrence rates by 57%. Further, women with the highest overexpression of HER2 (known as HER2 +3) had no cancer recurrences when they were administered the vaccine after completing trastuzumab (Herceptin), a type of immunotherapy drug known as a monoclonal antibody. HER2 is an oncoprotein that promotes tumor growth and is expressed to some extent in 75-80% of breast cancers.

“This is an important and different avenue in immunotherapy research, in that we are investigating ways to prevent cancer recurrence by stimulating the immune system to treat cancer,” says principal investigator Elizabeth Mittendorf, M.D., Ph.D., associate professor of Surgical Oncology. “The ultimate goal is to develop a preventative tool that will minimize the risk of recurrence in women who have already had breast cancer and for whom standard therapies have failed.”

The findings are the result of a phase II randomized trial that paired the GP2 vaccine, designed to stimulate the CD8+ cells, commonly known as “killer” or “toxic” T cells, with an immune stimulant known as granulocyte/macrophage colony stimulating factor (GM-CSF). The trial included 190 patients with varying levels of HER2; 89 women received the GP2 vaccine with a GM-CSF adjuvant and a control group of 91 patients received GM-CSF alone. Eight patients experienced early recurrence or developed a second malignancy and did not complete the vaccine trial. The vaccine is injected subcutaneously and the initial series consisted of monthly inoculations for six months, followed by four cycles of booster shots administered every six months thereafter. The patients were monitored for nearly three years.

For all 190 patients, including those who did not complete the trial, the disease-free survival (DFS) rate was 88% among those who received the vaccine and 81% in the control group — representing a 37% reduction in recurrence. Excluding the patients who did not complete the vaccine series, the results are higher — 94% DFS rate versus 85% who did not get GP2 — a 57% risk reduction.

Women with HER2 +3 who were administered trastuzumab as part of the standard of care prior to receiving the vaccine experienced no cases of cancer recurrence. According to Mittendorf, trastuzumab may act like a primer for the vaccine. Trastuzumab stimulates CD4+ T cells to release substances that fight cancer cells and initiates an antibody response. Thus, it may prepare the immune system, making the vaccine even more effective. MD Anderson is now testing this combination of immunotherapies in other clinical trials.

Personalized Immunotherapy

The GP2 study supports previous MD Anderson research on similar breast cancer vaccines, such as AE37, which showed a significant immune response and improved recurrence rates in triple-negative breast cancer patients. Another candidate, E75, known as NeuVax or nelipepimut-S, showed a 50% recurrence decrease in high-risk patients. Currently, NeuVax is being tested internationally in a phase III clinical trial.

“We believe many more patients will benefit in some way from immunotherapy,” says Mittendorf. “The challenge will be identifying the right immunotherapeutic approach for each individual patient. When doctors are able to do that, cancer therapy, and immunotherapy specifically, will follow a more personalized approach.”

source : http://www.sciencedaily.com/releases/2014/09/140905122717.htm

Blood test for ‘nicked’ protein predicts prostate cancer treatment response

The study evaluated two groups of 31 men with prostate cancer that had spread and whose blood levels of prostate-specific antigen (PSA) were still rising despite low testosterone levels. Investigators gave each man either enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, an indication that the drugs were not working. In the enzalutamide group, none of 12 patients whose blood samples tested positive for AR-V7 responded to the drug, compared with 10 responders among 19 men who had no AR-V7 detected. In the abiraterone group, none of six AR-V7-positive patients responded, compared with 17 responders among 25 patients lacking AR-V7.

Enzalutamide and abiraterone have been very successful in lengthening the lives of about 80 percent of patients with metastatic prostate cancer, says Emmanuel Antonarakis, M.D., assistant professor of oncology at Johns Hopkins, but the drugs do not work in the remaining 20 percent of patients.

“Until now, we haven’t been able to predict which patients will not respond to these therapies. If our results are confirmed by other researchers, a blood test could use AR-V7 as a biomarker to predict enzalutamide and abiraterone resistance, and let us direct patients who test positive for AR-V7 toward other types of therapy sooner, saving time and money while avoiding futile therapy,” says Antonarakis.

Prostate cancer thrives on male sex hormones (or “androgens”), including testosterone. Enzalutamide and abiraterone target proteins called androgen receptors and block the receptors’ ability to activate prostate cancer cells. AR-V7 is a shortened form of the androgen receptor that lacks a binding spot targeted by enzalutamide and abiraterone. With no binding spot for the two drugs, AR-V7 is free to manipulate prostate cancer cells’ genetic material, which makes the cancer cells grow and spread.

Antonarakis and his colleague Jun Luo, Ph.D., who first identified AR-V7 in 2008, also tracked patients’ progression-free survival (the length of time a patient lives with the disease but does not get worse) and overall survival. They found that, in men receiving enzalutamide, progression-free survival was 2.1 months in AR-V7-positive patients and 6.1 months in AR-V7-negative patients, while overall survival was 5.5 months in AR-V7-positive men and up to 9 months in AR-V7-negative men. Similarly, in men receiving abiraterone, progression-free survival was 2.3 months in AR-V7-positive patients and up to 6 months in AR-V7-negative patients, while overall survival was 10.6 months in AR-V7-positive men and up to 12 months in AR-V7-negative men. The investigators caution that most of the study patients had advanced disease and received multiple prior therapies, so their outcomes may not be generalizable to all men with prostate cancer.

“Patients whose blood samples contained AR-V7 got no benefit from either enzalutamide or abiraterone,” says Antonarakis. He adds that the shortened AR-V7 protein could appear in patients’ blood samples at the very start of therapy or acquired later, after therapy has begun. He says, “This test could be used before starting enzalutamide or abiraterone therapy, and if the test shows the presence of AR-V7, patients may opt for a different therapy. It could also be used to monitor patients receiving enzalutamide or abiraterone for AR-V7, providing an indication these drugs may not work for much longer.”

source : http://www.sciencedaily.com/releases/2014/09/140903203752.htm

Family conflicts, other non-physical worries before cancer surgery raise patients’ complication risk

The findings are published in the Journal of Gastrointestinal Surgery.

“We know that quality of life is a very complex thing, but we can now measure it and work with it almost like blood pressure,” says lead author Juliane Bingener, M.D., a gastroenterologic surgeon at Mayo Clinic in Rochester. “We can say, ‘This is good, this is in the normal range, but this one here, that is not good, and maybe we should do something.'”

Quality of life as measured in the study is about more than happiness and how well people feel physically, Dr. Bingener says. It also includes the financial, spiritual, emotional, mental and social aspects of their lives and whether their needs are being met.

Researchers studied 431 colon cancer surgery patients and found that before surgery, 13 percent had a quality of life deficit, defined as an overall quality of life score of less than 50 on a 100-point scale.

Nearly three times as many patients who entered surgery with a quality of life deficit experienced serious post-surgery complications as those with a normal or good quality of life score. Patients with a postoperative complication spent 3.5 days longer in the hospital on average than those who didn’t.

“The question I’m exploring is whether, if we understand before surgery that someone is in the red zone for quality of life, can we do something to help them cope with the new stress that’s going to come, so they’re better equipped to go through surgery?” Dr. Bingener says.

Preventing complications by intervening with behavioral therapy or other assistance would likely cost much less than an ICU stay for an infection after major surgery, Dr. Bingener notes.

Stress can weaken patients’ immune response, putting them at higher risk of infection. A patient’s outlook on life can also influence how active they are in working to recover.

“You have a surgery, you’re lying there in pain, now you wonder, ‘Why should I even get up and walk around? Why do I have to do these deep-breathing exercises? I don’t feel like it.’ You might get pneumonia much faster than somebody who says, ‘Oh, I have to get up. There’s something worth living for, my quality of life is good and I need to get back to that,'” Dr. Bingener says.

The study is part of ongoing work by Mayo to identify and address factors that can influence patients’ recovery from cancer surgery, to help improve their outcomes. Years ago, physicians were just concerned with whether patients survived cancer, because survival was so hard to achieve, Dr. Bingener says. Now, there is growing awareness of the mind’s influence on the body’s health.

“We’re understanding much better now that patients are not just a body with a disease: There’s a whole person with that, and everything plays together,” Dr. Bingener says. “Now that survival is possible, we want to achieve it in a way that preserves normal life for patients as much as possible. And we think that’s probably also the most economical way to go.”

source : http://www.sciencedaily.com/releases/2014/09/140902114416.htm