Older patients may require more supportive care, but they can often tolerate the same treatments as younger patients.
Approximately 60% of all new cases of cancer occur in patients aged 65 years
or older, according to a 1997 report in Cancer. However, research
into treating cancer in this age group is sparse, especially since older
patients are underrepresented in clinical trials. Defining terms such as
“elderly” and “frailty” can even be difficult.
According to the results of a 2004 study published in The Journal of
Clinical Oncology, patients aged 65 and older comprised 36% of patients
enrolled in clinical trials for cancer, but this age group represents 60% of
the total population with cancer.
Older patients often present with comorbidities that affect treatment
decisions and prohibit their participation in clinical trials. Diabetes or
congestive heart failure are adequate comorbidities to withhold certain
treatments from any patient with cancer, regardless of age, according to
Lodovico Balducci, MD, division chief of the Senior Adult Oncology
program at the H. Lee Moffitt Cancer Center in Tampa, Fla. Age alone, however,
is not a comorbid condition.
Lodovico Balducci, MD, is Division Chief of the Senior Adult
Oncology Program, H. Lee Moffitt Cancer Center in Tampa, Fla.
Photo by H. Lee Moffitt Cancer Center
“Unfortunately, in the past, many older patients have received less
treatment than younger patients despite being in overall good health,”
Balducci told HemOnc Today. “This is changing due to the
recognition that age is a functional aspect, not just a chronological
HemOnc Today has spoken with several leaders in senior adult
oncology to discuss issues in treating older patients, including what defines
elderly, the need for more data and ways to improve overall treatment for the
According to Balducci, age is defined by physiological and functional
changes, rather than by a chronological event. Although the majority of people
who are physiologically old are older than 70, not all people older than 70 are
elderly, he said.
There are no absolute age cutoffs to define elderly patients, according to
Stuart Lichtman, MD, an associate attending physician at the Memorial
Sloan-Kettering Cancer Center. It is a matter of differentiating between
patients who are resilient enough to receive active therapy as opposed to best
“If a patient is older than 80, then most of us will agree that he or
she is elderly,” Lichtman said in an interview. “The gray area is
patients aged 70 to 80 years.”
Medicare currently defines elderly by age, at 65 years. Sixty-five is also
used to define elderly patients in various research databases such as the SEER
According to Gary Lyman, MD, a professor of medicine in the division
of medical oncology at Duke University, the definition of elderly continues to
“It is apparent that as populations age, in general, people are more
health-conscious, people continue to work and are active well into their
70s,” Lyman said in an interview. “There is no uniform definition of
elderly. Many of us use age 70 to define a time where significant physiologic
changes start to take place, but the definition of elderly really is a
A person is not considered elderly until they have reached a point where
they cannot function independently, according to Balducci. He said that age 70
is typically a landmark when many people begin to develop severe comorbid
conditions that decrease life expectancy, including the symptoms of geriatric
According to Arti Hurria, MD, the director of the Cancer and Aging
Research Program at the City of Hope Cancer Center in Duarte, Calif., many
studies have shown that older adults are less likely to receive different types
of cancer therapy compared to younger patients. She said there are many
possible reasons for this, including patient choice, physician bias about the
risks and benefits of therapy, and the concerns regarding increased toxicity.
“A number of factors could come into play here, and the reasons for the
disparity in treatment require additional studies,” Hurria told HemOnc
Today. “One important variable to consider is access to care.”
Comorbid conditions play a large role in determining treatment for older
patients because they can have an effect on life expectancy, Hurria said. The
challenge lies in weighing the risk of dying of the cancer vs. the risk of
dying from another comorbid illness.
Although heart disease, diabetes and renal insufficiency, among others, have
clear influence on determining cancer treatment, frailty is a comorbidity that
is difficult to define and often overlooked, according to Lichtman.
Frailty can be defined in several ways, including presentation with
geriatric syndromes such as dementia, Lichtman said. Other signs of frailty
include a deficiency in the instrumental activities of daily living and changes
in gait and/or balance.
“Frailty is the comorbidity that affects this age group the most,”
Lichtman said. “The important issue is whether being frail makes an
elderly person more vulnerable to the toxicities of chemotherapy. Rudimentary
geriatric principles can be incorporated into practice to determine the frailty
of a patient.”
According to Hyman Muss, MD, a professor of medicine at the
University of Vermont, oncologists need to be trained to recognize the special
issues that pertain to older patients. These include frailty and the capability
to carry out activities of daily living.
“I always try to make sure I know what my patients can do,” Muss
told HemOnc Today. “Do they live by themselves? Do they
drive? Can they cook? What is the family structure? The average physical does
not encompass these things, but they influence treatment decisions also. A lot
of oncologists have not learned this.”
According to Muss, comprehensive geriatric assessments have been helpful in
predicting mortality in patients and at finding interventions to help people
who have lost certain functions. These assessments evaluate a variety of
domains in an older patient: comorbidities, physical function, medications,
nutrition, psychological state and social support. According to the CALGB, a
self-administered assessment is currently being evaluated in clinical trials,
“We hope this is a valid instrument to apply to older patients on a
regular basis that may help us predict which older patients are going to have
adverse effects to chemotherapy,” Muss said. “If we can predict, we
can do more to prevent.”
Comorbidities will weigh treatment decisions regardless of the tumor type,
Hurria said. For more aggressive cancers that severely limit a person’s
life expectancy, the effects of comorbidity on life expectancy may not be as
significant when considering treatment options. With a lesser-risk cancer,
comorbid illnesses may have a greater effect on life expectancy than the
cancer, Hurria said.
“How do we really counsel patients about their risk for toxicity
because of their comorbidities?” Hurria said. “We need to do more
research within the older patient population so we can really understand the
short- and long-term survivorship issues.”
Despite comprising the majority of the population with cancer, older
patients are severely underrepresented in clinical trials, according to
Balducci. He said there are two primary reasons for this. First, the inclusion
criteria of clinical trials often make an older patient ineligible. Second,
there is little motivation to enroll older patients into trials.
In a 2003 study published in The Journal of Clinical Oncology,
Lewis et al found that 32% of participants in phase-2 and phase-3 trials were
older adults, compared with the 61% of patients with cancer who are older
adults. The researchers estimated that if the inclusion criteria of clinical
trials were more relaxed and included more patients with comorbidities, the
older adult participation in clinical trials would be 60%.
According to Hurria, many physicians are concerned about subjecting their
older patients to the potential toxicity related to treatment during a clinical
trial. They want to ensure that the treatment risks do not outweigh the
potential benefits, Hurria said. As a result, they do not offer clinical trial enrollment to their older
Older patients want to participate, however. According to data published in
The Journal of Clinical Oncology in 2003, Kemeny et al found that
women older than 65 who had breast cancer were just as likely to accept
participation in a clinical trial as women younger than 65. However, only 34%
of the older patients were offered clinical trial participation vs. 68% of the
“We sometimes forget that cancer is a disease that increases
progressively with age,” Lyman said. “If we are not including these
patients in the clinical trials, then we are getting a biased picture of proper
treatment for the older patients. It is imperative for us to enroll older
patients because the results in younger patients may not be generalizable to
the majority of older patients.”
Barriers to enrolling older patients in clinical trials range from
ineligibility due to comorbidities, to physician bias, to lack of patient
understanding. According to a study recently published in the Journal of
Oncology Practice, 60% of patients older than 65 reported one or more
barriers to enrolling in clinical trials.
The most common barriers were logistical ones, such as traveling to the
cancer center. Patients older than 75 were also concerned about being treated
in a university cancer center and losing continuity with their oncologist.
“Many older patients are treated in community-oriented settings, so
participation in clinical trials can be more of a social issue,” Lichtman
said. “The nearest cancer center may not be local, so traveling to
participate in a clinical trial is a major burden. The burden is placed not
only on the patient but also the patient’s caregivers.”
As for physician bias, this is likely related to physician concerns about
protecting their older patients from toxicity and the rigors of clinical trial
treatment, according to Hurria.
“In this situation, the physicians are just trying to be good doctors
and not cause harm to their patients,” Hurria said. “But the studies
show that many older adults want to participate in trials. We need to build
safety parameters into our clinical trials so that older adults have access to
the same studies that younger patients do.”
According to Martine Extermann, MD, an associate professor of
oncology and medicine at the H. Lee Moffitt Cancer Center and also the
president-elect of the International Society of Geriatric Oncology, clinical
trials including only older patients are more common in Europe, where age is
permitted to be an exclusion criterion for clinical trials.
In the United States, carrying out elderly-specific trials is more of a
challenge, but may be the best way to identify ideal treatments for the typical
older population, she said.
“If we only do all-age inclusive clinical trials, we ignore a large
number of older patients with comorbidities,” Extermann told HemOnc Today.
“We currently extrapolate those data into practice, but what we need are
trials that lead to real data in real people with the same comorbidities. There
is a clear role for elderly-specific trials, especially since the population of
older people will only continue to grow.”
Balducci said that one solution is for the FDA to require drug companies to
conduct smaller phase-2 studies in older patients as a condition of drug
approval. If approximately 30 patients were enrolled in such trials, it would
be possible to determine whether a drug is effective and safe in that age
Elderly-specific clinical trials are feasible. At the 2008 ASCO Annual
Meeting, Muss presented data from the CALGB 49907 trial, one of the largest
trials ever conducted in the United States specifically in patients older than
65. The trial included 633 patients, although it did take longer than usual to
reach accrual goals, Muss said.
According to Hurria, the questions to be addressed in elderly-specific
trials include: What effect does the treatment have on the remaining quality of
life? What does the older adult really experience when undergoing treatment?
How does the treatment affect their ability to function?
“There are many clinically important questions that can be asked in an
elderly-specific trial that can help us guide treatment decisions for our older
patients,” Hurria said. “Furthermore, if we found a treatment that is
efficacious and had great short-term and long-term tolerability in older
patients, we would want to try that treatment in younger patients as well. The
idea is that we want every age group to have tolerable and efficacious
Nevertheless, older adults should also be enrolled more frequently on
non–age-specific trials to make results more generalizable, Hurria said.
Awareness and training are critical to improving the care of elderly and to
increase their enrollment in clinical trials.
“It is a challenge to overcome, but we are doing better,” Muss
said. “We need more education for our doctors to make them aware that
older patients benefit from treatment and clinical trials. Our younger doctors
in fellowship need to learn as well.”
Education, both in medical school and continuing medical education, is
necessary for physicians to evaluate patients for physiological age vs.
chronological age, according to Balducci. Lyman also said this is a
Extermann said that all oncologists need to learn at least the basic
principles of geriatrics. She suggested cross-training and multidisciplinary
efforts between oncologists and geriatricians.
Hurria said that all oncologists are also geriatricians, since the majority
of patients with cancer are older adults. Therefore, incorporating elements of
the geriatric curriculum in oncology training and CME activities would be
|Source: Cancer. 2002;94:-27922766 |
Balducci, who is chairman of the panel for the NCCN Senior Adult Oncology
Guidelines, said that one of the recommended updates to the guidelines is to
recommend that every patient older than 70 undergo a geriatric assessment to
assess their physiological age.
“This would be a simple way to help determine whether a patient is fit
enough for routine treatment,” Balducci said. “It is a very simple
process, and research is being conducted to see if it can serve as a predictor
of treatment response as well.”
Lichtman said that all older patients should be initially evaluated just
like younger patients, and this should include some form of geriatric
assessment. “At the end of the day, you may want to treat the patient
differently, but they still need to be evaluated just like a young
patient,” Lichtman said. “I see a lot of older patients who are not
evaluated properly. Once the diagnosis is made, then you can delve into
geriatric issues and determine whether they will tolerate therapy
According to Lyman, continuing research in elderly patients, especially the
use of novel targeted agents that are specifically designed to treat with less
toxicity, is also crucial to improving elderly care. According to Hurria, the
most important thing is to increase clinical research from several
perspectives, to understand what is the most efficacious treatment with the
least toxicity. The only way to do this is by increasing the enrollment of
older adults on clinical trials.
“We are facing a growth in the number of older adults with cancer in
the next 30 years,” Hurria said. “We want to make decisions about
their treatment in an evidence-based manner. The only way to do that is by
rapidly increasing our collaborative research efforts.” – by Emily
Should there be more
elderly-specific clinical trials?
For more information:
- Basche M, Barón AE, Eckhard SG, et al. Barriers to enrollment of
elderly adults in early-phase cancer clinical trials. Journal of Oncology
- Edwards BK, Howe HL, Ries LAG, et al. Annual report to the nation on the
status of cancer, 1973-1999, featuring implications of age and aging on U.S.
cancer burden. Cancer. 2002;94:2766-2792.
- Kemeny MM, Peterson BL, Kornblith AB, et al. Barriers to clinical trial
participation by older women with breast cancer. J Clin Oncol.
- Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years
of age or older in cancer clinical trials. J Clin Oncol.
- Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical
trials for cancer drug registration: A 7-year experience by the US Food and
Drug Administration. J Clin Oncol. 2004;22:4626-4631.