Posts tagged ‘research’

Complementary & Alternative Medicine Clinical Trials Influence Breast Cancer Care

Is low-level laser therapy an effective lymphedema treatment? Can acupressure reduce cancer related fatigue? Might green tea reduce breast cancer risk? These are among the more than 50 research questions now being studied in complementary and alternative medicine (CAM) breast cancer trials throughout the United States.

But it wasn’t always this way. Throughout the 1980s and early 1990s, most doctors, oncologists included, paid little attention to what were then thought of as “unconventional” therapies. But as public interest grew in alternative treatments such as vitamins and supplements, traditional Chinese medicine treatments like acupuncture, and mind-body therapies like yoga and progressive muscle relaxation, the mainstream medical field began to take notice.

The real wake-up call came in January 1993, when a research group from Beth Israel Medical Center in Boston published an article in the New England Journal of Medicine showing that a third of the roughly 1500 adults surveyed reported using at least one “unconventional” therapy in the past year, and that a third of these adults saw “unconventional” providers. With each visit costing about $30.00, this suggested that Americans were currently spending about $13.7 billion a year on these treatments.

Almost overnight it became clear that what many medical providers thought of as “unconventional” was routine for more of their patients than they had ever imagined. This awareness of the public’s interest in alternative treatments coincided with the increased realization that medical care needed to become more “evidence-based” with recommended treatments supported by clinical trials. In response to these trends, the National Institutes of Health created the National Center for Complementary and Alternative Medicine in 1998 to fund scientific research on the role of CAM in medical care. Funding was also specifically allocated for an Office of Cancer Complementary and Alternative Medicine (OCCAM) at the National Cancer InstituteAccording to the office’s most recent Annual Report, the NCI allocated $114,460,116 in 2010 to 406 CAM research projects. That year it also able to use $6,646,594 in funds from the American Recovery and Reinvestment Act to award 27 additional CAM research grants.

Learning What Works—And Doesn’t

Medical oncologist Debu Tripathy helped develop while on the faculty at the University of California, San Francisco (UCSF). Tripathy, now a professor of medicine at the University of Southern California Keck Medical Center, in Los Angeles, says there are two reasons CAM research is necessary: it’s already being used, and there is a need for more effective cancer treatments.

“CAM is already used widely … without it being clear what evidence there is to support it,” he says. “It’s possible that botanical or herbal agents may interact in negative ways with chemotherapy or other cancer treatments, and because people are already using these agents we need to understand whether they are effective or not and how and in what individuals. … There also are areas of great need where our current treatments are not very effective,” such as reducing the side effects of chemotherapy. “We need to broaden the search and look at alternatives that may be effective.”

The research done to date has already pointed to new possibilities. Studies have found, for example, that acupuncture reduces joint pain in some women with breast cancer, an ancient four-herb Chinese Medicine formula called PHY90 reduces chemotherapy-related side effects, weight lifting does not exacerbate and may improve lymphedema after breast cancer, and hypnosis before breast cancer surgery reduces pain and discomfort—and more results are on the way. (These and other CAM research results are available here.)

These and other findings have the potential to improve cancer patients’ quality of life during and after treatment. But, notes Tripathy, what many patients want to know—and what is less often funded—are trials that look at CAM treatments that have the potential to slow or stop a tumor’s growth. “I think it is those kinds of studies that patients are interested in,” he says.  They are happy to know that “massage therapy might make me feel better, but when it comes to sorting through claims about what has an anti-cancer effect”—we haven’t had those trials.

As with much of cancer research, the problem comes down to funding. Larger trials are necessary to show that a treatment is effective against cancer, but these trials take a lot of time and money. Pharmaceutical and biotech companies fund them because there is the potential to earn back what they spend—many times over—with a top-selling drug. But the same isn’t true for CAM. This is why, says Tripathy, “there are tons of early phase CAM trials, but so many fewer that go beyond the pilot state.” There have been phase III trials “that have looked at diet and exercise, and those have led to actual recommendations.” But that’s been the exception, not the rule.

Richard Lee, the medical director of the Integrative Medical Center at M. D. Anderson Cancer Center, in Houston, is on the frontline of the incorporation of evidence-based CAM into cancer care. Has he found oncologists in the U.S. to be more accepting of CAM than they used to be? “Yes and no,” he says. “CAM is such a broad term and it incorporates a variety of therapies. Oncologists are understanding more about the value of therapies like meditation and yoga. Certain things like acupuncture are gaining more acceptance. And some areas, like herbs and supplements and energy healing, remain controversial.”

Finding a CAM Trial

Since its launch, BCT has seen interest in CAM trials grow. To make finding these trials easier, BCT developed a CAM QuickView that provides one-click access to a list of all open CAM trials taking place at research centers throughout the country.

Julia Wiley, 47, was diagnosed in July 2010 with metastatic breast cancer. Since then, she has taken part in two treatment trials at UCSF. She also enrolled in a CAM trial at the Stanford University School of Medicine Center on Stress and Health, in Palo Alto, studying the relationships between stress, quality of sleep, hormones, immunity, and cancer progression. She learned about the study from a friend who had enrolled, and then went on to tell others about it as well. “I like contributing to research,” says Wiley, whose family owns an organic farm in Watsonville, Calif. “I also liked that this study didn’t require me to take another chemical and was looking into something that interested me.”

M .D. Anderson currently has four CAM studies open, and at least two more will be opening soon. One, says Lee, will study acupuncture for treating chemotherapy-induced peripheral neuropathy, while another will look at the effectiveness of an integrative care program that incorporates exercise, nutrition and stress management. Lee has found that breast cancer patients who are eligible are often interested in enrolling in trials. “Clinical trials are such a crucial part of advancing the field,” he says. “I appreciate those who have enrolled in trials and who are willing to collaborate with us to make a difference for the next person who is going to be diagnosed with cancer.”

For more information about OCCAM and to see research results from CAM studies, visit the OCCAM website:

August 29, 2012 at 8:58 pm 2 comments

Q & A with Ann Fonfa

Ann Fonfa is the founder and president of The Annie Appleseed Project, which provides evidence-based information for cancer patients about complementary and alternative medicine (CAM). The organization’s first-ever west coast conference will take place September 14-15 at The Event Center at St. Mary’s Cathedral in San Francisco.  

Ann became interested in complementary and alternative therapies after she was diagnosed with breast cancer in 1993 at age 44. Ann recently spoke with BCT about her efforts to draw attention to and increase evidence-based research on CAM.

Q: Why is it important to have evidence-based CAM research?
A: One reason is that doctors won’t be convinced unless they see level 1 evidence that comes from a randomized trial. There are more studies being done, but some doctors still consider some of the outcomes not acceptable because there is no level 1 evidence.

Q: Would you encourage someone to get involved in a CAM clinical trial?
A. Yes, and we try to list them on our website. I think the most important thing is that everyone make informed decisions about their treatment. … I also think integrative medicine (which combines mainstream treatments with CAM) should be offered to everyone.

Q: What do you expect will be some of the highlights of the conference?
A: Michael Lerner, the co-founder of Commonweal will be there, along with Donald Abrams, the director of clinical programs at the University of California San Francisco Osher Center for Integrative Medicine. We will have a patient panel, because the patient voice is so important, as well as sessions on Qigong, pilates, and yogic breathing.

We have scholarships available for local cancer patients. The information is available on the Annie Appleseed website.

August 29, 2012 at 8:39 pm 1 comment

Phase I Clinical Trials – A Changing Paradigm

Phase I clinical trials for cancer have traditionally focused on testing the safety of new drugs, enrolling only patients in advanced stages of disease who were counseled not to expect any personal benefit. As more targeted or “personalized” therapies emerge from the laboratory, the design of Phase I clinical trials is evolving to allow investigators to begin to look more closely at efficacy (how well a tumor is responding to therapy). In addition, investigators are testing not only new drugs but those that the FDA has approved for different types of cancer, which are now being studied in combination with previously approved breast cancer therapies.

Jennifer Wheler, MD

“The first thing I tell my patients is that Phase I trials come in all shapes and sizes,” says Jennifer Wheler, MD, Assistant Professor in the Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at the University of Texas, MD Anderson Cancer Center, in Houston, Texas. “With targeted therapies the old way of running clinical trials with Phase I, Phase II and Phase III components is becoming outdated,” she adds. According to Wheler, the important work now is to profile a patient’s tumor so that targeted therapies can be tested on individuals and personalized to the aberrations that are apparent in their disease.

“For instance, the PI3K pathway is an important aberration in breast cancer,” says Wheler, “and we’ll probably find that a significant proportion of breast cancer patients have an aberration in this pathway. This essentially means that targeting it with a new drug would be a useful thing.”

Wheler is currently lead investigator for a trial at MD Anderson (similar to Bolero-2, which was a Phase III trial for advanced breast cancer patients) that has enrolled over 100 cancer patients to test Anistrozole (Arimadex®), an anti-hormone therapy agent, in combination with Everolimus (Afinitor®), a therapy targeted to cellular growth. In this particular study, if a patient develops resistance to either of the two drugs, then the strategy is to add a third drug to try and overcome the resistance. This means that treatment in this Phase I trial is truly tailored to both a patient’s tumor biology and her response to therapy.

Pam Munster, MD

“Many patients will never consider a Phase I trial because they believe the drug being tested will be in such an early stage of its development that they will not benefit from taking it,” says Pam Munster, MD, Director, Early Phase Clinical Trials Unit and Leader, Developmental Therapeutics Program, at the University of California San Francisco, Helen Diller Family Comprehensive Cancer Center. “But we really try to make every effort to select the right drugs for patients, so they at least have a chance of a good response.”

Both Munster and Wheler assert that early studies involving new drugs are always carefully designed to monitor safety. The first patients admitted into a Phase I trial receive a very small dose of the drug. Only when investigators are satisfied that the side effects are not harmful, is the dose gradually increased or “escalated.” This is done until they have identified the highest dose that can be tolerated without side effects.

“We look very closely at the preclinical safety studies,” says Munster. “And we will take patients off a study as soon as we find out it is not helpful to her.”

For a patient, a Phase I trial may be the best chance she has to experience a new drug. This is because a patient accepted onto a Phase I trial is sure to receive a new drug. Someone who waits until the drug is tested in a Phase III trial may either not be eligible for the trial because of number of prior treatments or may end up randomized to a control group receiving the standard treatment of care or sometimes a placebo. There are no control groups in Phase I trials; everyone receives the drug.

The patients Munster enrolls in her trials tend to be those at the end stage of their disease who come onto a Phase I trial as a last resort. She explains that these individuals often have severely compromised overall health and are frequently very sick, which means it is hard to truly test the efficacy of the targeted drugs.    She believes that she would see better responses in patients whose disease had not progressed so far already.

“We would like to see patients at least considering a Phase I trial earlier in their treatment history,” says Munster. “In particular, now because there is more potential for her to personally benefit from therapy if appropriately selected.”

May 16, 2012 at 10:19 pm 1 comment

The Rise and Fall of the Radical Mastectomy

And the Clinical Trial that Led to Its Demise

For most newly diagnosed breast cancer patients, the option of breast conserving surgery (lumpectomy followed by radiation or simple mastectomy) is taken for granted. But that was not always the case. Forty years ago radical mastectomy was the standard of care. It took a controversial and landmark clinical trial to spare women from this unnecessary and disfiguring surgery.

William S. Halsted, an accomplished young surgeon at Johns Hopkins, first performed the “radical mastectomy,” also known as the Halsted procedure, in 1882. With surgery as a breast cancer patient’s only option, a woman treated by Halsted (and the many surgeons who followed his method) not only had her entire breast removed, but also the surrounding tissue, lymph nodes and the pectoral muscles. Halsted hypothesized that breast cancer grew in a slow, orderly way, spreading from the breast to the lymph nodes and finally to other parts of the body. Despite the resultant disfigurement, Halstead believed that the more extensive the surgery, the less likely the cancer would be to return.

Halsted’s procedure and his belief about the pathology of cancer persisted among physicians in the United States for a very long time. It was not until 1951 that another cancer surgeon seriously challenged Halsted’s underlying assumptions.  Ian MacDonald, a Canadian teaching in Los Angeles, argued that the relative aggressiveness of breast and other cancers was biologically determined and did not necessarily conform to Halsted’s “one size fits all” model of growth. That being the case, radical mastectomy might not be necessary for all women, especially those with slow-growing tumors.

Relatively few surgeons supported MacDonald’s theory. One of them was George “Barney” Crile, Jr., whose father, also a cancer surgeon, was renowned for describing in horrific detail the effects of radical mastectomies on his patients. In the early 1950s, Crile, Jr., became the first surgeon in the United States to offer women a choice – radical mastectomy or simple mastectomy. He performed his last radical mastectomy in 1954. Praised for his actions by a small but vocal group of patients, Crile’s less extensive simple mastectomy was vigorously attacked by his colleagues, some of whom considered it “equivalent to malpractice.”

By the 1960s, the lines were drawn: surgeons were either for or against radical mastectomy citing published case reports based on their own subjective clinical experience. At the same time, breast cancer patients increasingly began to question the efficacy of the Halsted procedure. Among the clamor, another group argued that the only way to objectively determine the effectiveness of radical mastectomy was through a randomized clinical trial, a relatively new concept at the time (Note: The first clinical trial was conducted in 1948 to evaluate the use of streptomycin for tuberculosis). But many physicians disagreed with the whole notion of gathering objective evidence: they didn’t support patients being randomly assigned to one surgical procedure or another nor would they trust the results, preferring to rely on their own experiences of working with patients and monitoring outcomes.

If ever there was a person to unite the contentious parties, it was Bernard Fisher, a prominent surgeon-scientist. Starting in 1958, Fisher pursued a life-long interest in breast cancer research straddling both the laboratory and clinic. From laboratory studies on tumor metastasis, he theorized that breast cancer was a systemic disease and that those women associated with poor survival outcomes were likely to have undetected tumor cells that had already spread to distant organs at the time of diagnosis. If this was true, then radical mastectomy was unlikely to improve outcomes over simple mastectomy.

Eager to apply scientific principles to his hypotheses, in 1967, Fisher became the first chair of National Adjuvant Breast and Bowel Project (NSAPB). Under his leadership NSABP launched NSABP-04 in 1971, the first randomized trial in America that compared radical mastectomy with simple mastectomy or simple mastectomy followed by radiation therapy. Published in 1974, its early results based on findings from 1,700 patients enrolled at 34 institutions, showed that the survival outcomes for patients were the same regardless of which type of treatment was performed.

Despite the mounting evidence to the contrary, many surgeons continued to advise their patients that the Halsted procedure was in their opinion the ‘safest’ treatment. But as later results from NSABP- O4 and other trials confirmed the efficacy of the simple mastectomy, the medical profession altered its standard treatment for breast cancer patients. In 1983, there were only 5,000 radical mastectomies performed in the country (down from 46,000 in 1974).

The controversy surrounding radical mastectomies has had far reaching consequences that continue to be felt. Not only did it pave the way for the acceptance of clinical trials as the standard by which all advances in breast cancer are evaluated ( currently lists over 500 U.S. breast cancer studies), but it also empowered women for the first time to talk openly about their experiences of breast cancer and to be actively involved in their care. With their “collective voice,” these women found a place at the table alongside health policy makers, funders, and research investigators. Breast cancer patient advocacy had been born.

Further Reading

The Breast Cancer Wars: Hope, Fear, and the Pursuit of a Cure in Twentieth-Century America Barron H. Lerner, Oxford University Press, 2001

Bernard Fisher Reflects on a Half-Century’s Worth of Breast Cancer Research Interview with Kate Travis, 2005

The Emperor of All Maladies: A Biography of Cancer, Siddhartha Mukherjee, Simon & Schuster, Inc., 2010  

December 1, 2011 at 8:01 pm Leave a comment

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