Frontiers

Barbara Beckwith is a retired elementary school reading teacher who felt passionate about the importance of books in her students' lives. Now as a 10-year breast-cancer survivor, she's teaching with passion again, this time about the importance of clinical trials and the need for older people and African Americans to participate in them.

As a breast cancer prevention educator with the Columbus Community Clinical Oncology Program, she's become a grass-roots health advocate, going from neighborhood to neighborhood in Columbus, talking with young and old alike about the importance of cancer prevention and the benefits of participating in clinical trials.

“I give people background information on the basics of clinical trials and why it is so important to participate in these studies,” she says. “I know the medications I took were available because someone else had to test those drugs. That's why I'm truly an advocate for clinical trials.”

Beckwith, 68, is doing important work in the community. Clinical trials determine the safety and effectiveness of drugs and other medical therapies in human volunteers. Clinical trials are used to test ways to prevent and treat cancer, and to improve quality of life after treatment. They are critical for determining whether potential new drugs are more effective and have fewer side effects than current medications. No drug, however, works the same in everyone. A new anti-cancer drug might or might not have the same effect in men and women, different ethnic groups or younger and older adults.

For example, anticancer drugs might behave differently in older and younger patients because the bodies of older people might metabolize a drug differently, or the new drug might interact with medications an older person may be taking for another condition, such as diabetes or heart disease. Then, too, the tumor itself may behave differently in an aging body.

So it’s important that a clinical trial include the range of people who will use the drug being tested. This is especially true for people over 65 – the fastest-growing segment of the cancer population.

Today there are roughly 35 million people 65 and older in the United States. The first wave of baby boomers turns 65 in less than seven years; this generation will ultimately add about 75 million people to the older population by 2030.

Cancer is a disease mainly of the aged, and as the number of older people rises, so will the number of people with cancer. In 2000, the American Cancer Society expected some 389,000 persons 75 years and older to be diagnosed with cancer. That number is expected to increase to about 1.1 million by 2050, with the number of cancer patients aged 85 and older expected to quadruple during the same period.

“Elderly people already make up the largest segment of the cancer population, and we have yet to define the optimal treatments for many of them,” says Charles L. Shapiro, MD, director of breast medical oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University.

At the same time, he says, “clinical trials often exclude people age 65 and over because of a perception that elderly patients are frail and can't handle aggressive therapies. So we often extrapolate results from younger patients to older patients, which may work in many cases. But older patients might also benefit – or not benefit – from therapies that work in younger persons.”

Today, more than 60 percent of all cancer patients are 65 and older, but only 25 percent of people participating in clinical trials are in this age group. And a yearlong National Cancer Institute Cooperative Group trial found that less than 1 percent of people 70 and older with cancer participate in clinical trials.

Elderly people have historically been excluded from clinical trials for a variety of reasons, ranging from poorer health due to other illnesses to the logistics of transporting a patient to and from the trial site. But perhaps the main obstacle is the sheer diversity of this group, says Lodovico Balducci, MD, program leader of the Senior Adult Oncology Program at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

“The older population is so diverse in terms of health, function and resources from one person to the next that it's very difficult to use one approach in determining what an individual can handle, and also whether the treatment may be more beneficial than detrimental,” Balducci says.

Many physicians and patients believe that experimental therapies, which may have some unknown side effects, are not appropriate for elderly cancer patients. Many physicians also presume that older patients would be unwilling to undergo aggressive chemotherapy if offered. Consequently, elderly patients often don’t learn their full range of treatment options.

That wasn’t the case for breast-cancer survivor Patricia Reichelderfer, 69, who immediately said yes when her doctor asked if she wanted to take part in a trial testing an oral chemotherapy drug for early stage breast cancer. The drug, Xeloda®, was already proven effective in the treatment of advanced breast cancer. Reichelderfer saw two brothers go through chemotherapy and succumb to lung cancer; she lost another brother to diabetes.

“When I was asked to go into the trial, it was a no-brainer,” she says. “Somebody went through a trial to help me, and now I could help somebody else. Older people have a duty to help out.”

Whether elderly patients can tolerate chemotherapy is the subject of a growing number of studies. Italian researchers have found, for example, that people 70 and older with high-risk stage II or III colon cancer, who were in otherwise good health, tolerated chemotherapy just as well as people younger than 50. Chemotherapy also helped reduce the risk of cancer recurrence equally well in both age groups. A study published in the New England Journal of Medicine, which involved more than 3,000 patients, confirmed that elderly people who received chemotherapy following surgery for colon cancer benefited from the treatment just as much – and tolerated it just as well – as younger patients.

But age does bring inevitable limitations, says Lilia Talarico, associate director in the Division of Oncology Drug Products of the Food and Drug Administration's Center for Drug Evaluation and Research. “Bone marrow function naturally declines with age. Since chemotherapy puts heavy demands on bone marrow, an elderly person may experience a more severe and longer-lasting marrow suppression from treatment.”

Researchers from Dartmouth Medical School reported that women with illnesses such as heart disease, diabetes or high blood pressure were 20 times more likely to die from these diseases within three years than from breast cancer.

“If a person has a history of heart attacks or congestive heart failure and they get cancer, their mortality might be more related to their heart problems than to cancer,” Shapiro says. “But there are a significant number of adults in their sixth, seventh, even eighth decades have few or no medical problems. Still, these people have an increased risk of developing cancer due to age alone.”

An FDA study of nearly 30,000 people enrolled in clinical trials testing new cancer treatments found that chemotherapy was prescribed far less in people 65 and older.

“There are some valid reasons for this,” says Talarico, the study’s lead author. “Elderly people are more likely to have pre-existing medical conditions. They may choose not to undergo treatment. And physicians may fear making their elderly patients sicker. However, older people can and should be assessed for their ability to tolerate chemotherapy.”

“People who undergo aggressive cancer treatment require a lot of care – the patient needs transportation to and from a clinic, easily accessible hospital care and family support,” she says.

The logistics and extra cost associated with participating in clinical trials may keep some elderly people from joining. As older people may be more vulnerable to complications, they may need more supportive care, and treatment benefits may be less because of reduced life expectancy and the presence of other chronic illnesses.

The Clinton administration in 2000 mandated that Medicare cover all clinical trial related treatments; according to the insurer's website, it covers “patient care costs in clinical trials, including items and services that it normally covers when the care is taking place outside of a trial.” But additional care and therapy, such as drugs to treat nausea or infections, transportation to and from a clinic, or care at home may not be included.

Expenses covered by treatment trials typically include the experimental drug itself or an inpatient hospital stay if the trial requires one. Any procedure that a patient would normally undergo as part of his usual or standard care, such as CT scans and blood tests, is usually covered, too. And the trial’s sponsor often covers extra tests that are solely related to the trial, Shapiro says. But health complications that arise while a patient is in a study generally aren’t covered by participation.

Concurrent illnesses and logistics aside, a lack of understanding can keep people from joining clinical trials. Patients may simply not know that trials exist or have misconceptions about what they are.

“No one had ever talked to me about a clinical trial when I was first diagnosed,” says Beckwith. “I had already undergone radiation therapy by the time I saw my medical oncologist, who told me about a trial. But I no longer fit the protocol for the study because I had already received treatment. That was the first time I had ever heard anything about clinical trials.”

Jacquelin Holland, a nurse practitioner for 30 years and program director of the Diversity Enhancement Program at the OSU James Cancer Hospital and Solove Research Institute, along with Beckwith and other volunteers, is working to boost knowledge and awareness of clinical trials in the community.

Holland runs Grandma’s Hands, a program sponsored by the James Cancer Hospital and the Columbus affiliate of the Susan G. Komen Breast Cancer Foundation. Grandma’s Hands educates African- American women age 50 and older about the importance of cancer prevention and clinical trials (see sidebar).

Beckwith is a Grandma's Hands volunteer. “It’s a sad thing that many people aren’t introduced to trials until something is wrong with them,” she says. “Having cancer is enough to deal with, and then you’re going to ask me to also be a part of something I’ve never heard about? That’s why I’m out in the community talking about clinical trials.”

After recovering from breast cancer, Beckwith participated in a quality of life study for African-American cancer survivors and is currently part of two other studies. One of those is the National Cancer Institute's National Lung Screening Trial, which screens for lung cancer; the other examines sexuality in the aftermath of cancer.

Understanding what a clinical trial is before the need arises to join one is especially important for older people. The decision to put older patients through chemotherapy can be especially complex. Older patients may have undiagnosed chronic diseases, for example, so the possibility of death unrelated to their cancer is greater. Also, the benefits of chemotherapy may be less and the potential side effects of treatment may be greater for older people.

“It’s really a question of what ‘elderly’ means – it doesn’t have the same connotation it did 20 or even 10 years ago,” says M. Margaret Kemeny, MD, director of the Queens Cancer Center of Queens Hospital and a clinical professor of surgery at the Mt. Sinai School of Medicine in New York City. “More older people are staying healthier longer. And we’re certainly going to see many more very old people in the next 20 years. We have to figure out what to do when these people get cancer, which a number of them will.”

Kemeny studied the barriers that kept elderly women from inclusion in a number of breast cancer trials conducted at 10 research institutions. The main reason for exclusion wasn't that the women didn’t want to join the trials – half of the older women said they would have joined if asked. Instead, their physicians thought the elderly women couldn't handle the experimental therapies.

“It’s a matter of educating physicians on what elderly patients can and can't tolerate,” she says.

Research by Shapiro showed something similar. In a study of 480 women, he and his colleagues found that women over 65 who were candidates for chemotherapy were up to seven times less likely to receive chemotherapy following breast-cancer surgery than were women under 50.

“Making treatment decisions on the basis of age alone, which is called age bias, may influence whether or not older women receive adjuvant chemotherapy treatment,” Shapiro says.

A degree of fear may also keep older people from joining clinical trials, says Beckwith. “With anything that's a mystery, people tend to draw back and put up a wall. There are lots of people with the attitude that ‘if it's not broke, don’t fix it.’”

Charles McMurray, a 79- year-old survivor of both colon and prostate cancer, says he would have felt apprehensive to try an experimental therapy when he underwent treatment for both diseases.

“At the time I would have been inclined to go with what was already working for other cancer patients,” says McMurray. “But I’m here as a result of someone being involved in clinical trials for chemotherapy. So yes, I think trials are very important.”

Conversely, Reichelderfer had no apprehensions when her doctor asked if she would join the Xeloda® treatment trial. “I’d advise anybody to go into a trial,” she says. “My doctors told me that if they thought the treatment wasn’t working, they would do something else.” Shapiro notes that before entering a clinical trial, physicians should thoroughly explain the risks, costs and benefits of the trial, that patients must provide their informed consent before joining a study, that patients can stop participating in a study at any time and for any reason, and that their doctor will continue providing them with the best care possible. Strides in technology and medicine even in the last five years may make clinical trials a much more viable and attractive option for older cancer patients.

“This is a population in need of treatments that aren’t always available,” Talarico says. “But treatments are improving.”

Current cancer drugs are more targeted to the disease and are also tolerated better by the elderly. Older people can and should be assessed for their ability to tolerate chemotherapy.”

As life expectancy in the United States increases – it grew from 47 years at the turn of the last century to 74 for men and 79 for women by 1999 – so does the need for knowing how to treat cancer and the other health problems of older people.

“We can make progress against cancer only by testing new therapies and approaches in clinical trials on the people who will benefit the most from them,” says Shapiro.

Older and younger patients may differ in many ways, but both value the possible benefits of effective cancer therapy. To quote an editorial in the Journal of Clinical Oncology supporting aggressive cancer treatment in fit elderly people with lung cancer:

“A 75-year-old person wants to be a 76-year-old person as strongly as a 55-year-old person wants to be a 56-yearold person.”  ■

Written by Holly Wagner
Illustrations by Rick Lillash

GRANDMA’S HANDS
A clinical trials research education program

"Grandma's hands clapped in church on
Sunday morning…
Grandma's hands used to issue out a warning…"
-Bill Withers,
"Grandma's Hands"

"Grandma's Hands" is the brainchild of Jacquelin Holland, a nurse practitioner and program director of the Diversity Enhancement Program at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University. Through Grandma's Hands, Holland and volunteers aim to educate 500 African American women age 50 and older about cancer awareness and participation in clinical trials.

"Research is something that not only may make a difference in your health, but also in the health of your own family," she tells her audiences. "And every medication you use or have ever used had to be tested on someone."

Holland clears up common misconceptions about clinical trials – she tells Grandma's Hands participants that people in trials testing a new cancer treatment are given sugar pills, or placebos, only if a drug is unavailable for their type of cancer. She also makes the important point that a participant can withdraw from a trial at any time, even before the trial starts. She explains that it takes on average 15 years for a new drug to go from its discovery to the consumer, and that brand-new treatments aren't always better than standard treatments. She warns that new treatments may have unexpected side effects, they may not work for everybody and there may be additional costs.

She also tells the audience that there are over 100 different kinds of cancer, and that every person diagnosed with cancer should be told about clinical trials, whether or not a trial is available to treat her particular disease. "A doctor needs to give you all of your choices," Holland says. "And if he or she doesn't bring it up, then you need to bring it up and ask questions."