Treatment and the age factor

<http://www.curetoday.com/currentissue/features/feature3/index.html>
the age factor
By Charlotte Huff

The tumor in Jean Caldwell?s breast measured 4 centimeters. And that
wasn?t the only bad news. First, the Wisconsin grandmother underwent a
lumpectomy last summer. Then, when further tests revealed the cancer had
spread to several lymph nodes, the surgeon removed nearly two dozen, along
with her left breast.

Like any case of stage 2 breast cancer, the treatment options were
complex. But Caldwell faced another reality?her age: 76. James Stewart,
MD, her oncologist, met with Caldwell and her children several times as
they discussed the relative risks of various chemotherapy regimens,
including potential heart problems. Caldwell didn?t waver. With three
children and four grandchildren in her life, she didn?t want to hedge her
bets.

?I wanted to be as aggressive as I could, because I want to be cured and I
want to live,? she recounts. ?I said to my doctor, ?I want to do
everything I can.? He said he would go for the cure.?

Traditionally, cancer has been associated with later life. More than
half?56 percent?of all diagnoses are in Americans 65 and older, according
to the National Cancer Institute?s Surveillance, Epidemiology, and End
Results, or SEER, data. The median age at diagnosis is 67, but demographic
trends, led by the Baby Boomers, will soon boost the sheer number of older
cancer patients dramatically. According to one study?s projections, the
number of newly diagnosed Americans age 75 and older could number nearly
1.1 million in 2050 compared with an estimated 389,000 in 2000.

That surge in patients, physicians say, will likely outpace the knowledge
necessary to treat a very complex and diverse patient population. For
every elderly cancer patient who struggles to live independently, another
may hold down a job and play tennis three times a week. Diagnosis and
treatment can be delayed or complicated by other medical conditions.

Meanwhile, most chemotherapy and other research trials generally include
only the fittest of seniors, if they?re enrolled at all.

Just 32 percent of participants in late-phase clinical trials are age 65
and older, according to a study published in 2003 in the Journal of
Clinical Oncology.

Within the past five years, more researchers have strived to include older
patients, says William Ershler, MD, senior investigator in the clinical
research branch at the National Institute on Aging. Several groups,
including the International Society of Geriatric Oncology and the
Geriatric Oncology Consortium, are working to boost research and physician
training, he says. In 2003, the NCI and the NIA jointly sponsored a
five-year, $25 million grant program focused on cancer and aging issues,
including treatment, side effects, pain relief and psychological stresses,
among others. Eight cancer centers received awards under the program and
are currently conducting research in these areas.

Still, Dr. Ershler believes there?s room for improvement. ?There is a bias
I have been fighting against treating older people,? he says. ?I think
many tumor types are very responsive to treatment. And, for some arbitrary
reason, they are not offered to older people. It oftentimes comes from the
families of the patient. It oftentimes comes from the nursing staff, who
says, ?You?re going to do what to whom???

In Dr. Ershler?s experience, ?Almost invariably, the patient says, ?I want
to be treated aggressively.??

Age and Cancer

For many of the common cancers, the development of a tumor takes
considerable time, dependent upon a series of often unrelated events on
the cellular level, Dr. Ershler says.

Nearly 71 percent of colon cancers are diagnosed in Americans age 65 and
older, according to SEER data. So are 68 percent of lung malignancies and
64 percent of prostate.

A number of cellular influences may be involved, researchers say. Over the
course of years, genetic and environmental toxins, such as tobacco
carcinogens, can cause DNA-damaging effects on cells. Meanwhile, the
body?s ability to repair damaged cells appears to decline with advancing
age, Dr. Ershler says.

At the same time, the aging tissue around those damaged cells appears to
play a role, creating a more conducive environment in which malignancies
can grow, says Harvey Cohen, MD, director of the Center for the Study of
Aging and Human Development at Duke University Medical Center. As cells
age and stop dividing, it?s speculated that they develop a
microenvironment that fosters cancer?s development, he says.

Another potential contributory factor, researchers say, is the declining
immunity that naturally occurs with advancing age, although not everyone
is convinced. Dr. Ershler, for example, believes any decline in immune
function is not significant enough in most older people?barring an organ
transplant, HIV or other immune-compromised condition?to spur cancer?s
development. And not every malignancy is associated with advancing age.

Some malignancies, such as acute leukemia or Hodgkin?s disease, are more
frequently diagnosed in younger adults, in part because they require fewer
cellular changes to develop cancer, Dr. Ershler says.

Once they take root, Dr. Ershler believes cancers are less aggressive in
older patients than in their younger counterparts. He says some of the
most common cancers are slower growing and slower spreading, which he
attributes to the less fertile environment in aging tissue, with fewer
growth and other factors that could stimulate cancer growth.

Other researchers, though, express caution. ?With the exception of breast
and lung cancer, I think other cancers are worse in older people or not
any better,? says Lodovico Balducci, MD, another leading researcher in
cancer and aging. And some breast and lung malignancies may have developed
earlier in life, but because of their slow-growing nature, might not have
been identified until later years, he says.

Assessing Patients

Sometimes the aches and other discomforts of advancing years can mask
cancer symptoms and, thus, the diagnosis, says Dr. Balducci, head of the
Senior Adult Oncology Program at H. Lee Moffitt Cancer Center in Tampa.
Constipation may be written off as normal, or new bone pain may be
attributed to arthritic joints. That?s why regular screening is crucial,
he says.

Once a patient is diagnosed, an oncologist must consider several factors
as treatment options are discussed. Will the cancer shorten the patient?s
life expectancy or, will they most likely die of something else? Even if
their life might not be cut short, will the tumor make their remaining
years more miserable? And, is the patient healthy enough to withstand the
treatment itself, as well as any long-term consequences?

Given the relatively long survival for early-stage prostate cancer, for
example, it can make sense to closely watch the malignancy in older
patients, only treating when necessary, Dr. Balducci says.

Age may also play a critical role in the decision of whether to give
chemotherapy following surgery, known as adjuvant treatment. Adjuvant
chemotherapy in a 70-year-old woman allows for a small reduction in the
risk of dying of breast cancer, but also carries a small but worrisome
risk of complications, including developing heart damage or even acute
leukemia, he says. Meanwhile, not all 70-year-olds have the same health
status, even before cancer looms.

Oncologists could benefit from a quicker analysis, one that could
be done in the doctor?s office to gain a snapshot of the patient?s ability
to withstand the rigors of treatment. Dr. Extermann is working on such a
shorthand test.

Geriatricians will often refer to a patient?s functional age?an estimation
of a patient?s relative fitness and frailty?along with their calendar age,
and use a comprehensive series of tests to determine their functional
abilities. These functional tests look at everything from mobility and
comorbidities to cognition and social support.

Oncologists could benefit from a quicker analysis, one that could be done
in the doctor?s office to gain a snapshot of the patient?s ability to
withstand the rigors of chemotherapy and other treatment, says Martine
Extermann, MD, PhD, an associate professor of oncology and medicine at
Moffitt Cancer Center. Dr. Extermann is working on such a shorthand test,
one she hopes will require just five minutes, similar to how the Apgar
scoring is used to quickly assess a newborn?s condition immediately after
delivery.

The functioning test would help sort out those patients in vigorous health
from those who require additional scrutiny, Dr. Extermann says. About half
of older patients likely would require a more detailed functional
assessment, she says.

After recovering from two operations, first a lumpectomy and then a
mastectomy, Jean Caldwell recalls Dr. Stewart asking, ?Are you ready to go
on?? Yes, she responded.

Dr. Stewart, medical director of the University of Wisconsin Breast
Center, has treated some older patients with portions of the multi-stage
treatment Caldwell is undergoing. Caldwell, he says, remains one of the
oldest to receive all of the medications. Her cancer is potentially
curable, he points out. She?s in excellent health and could potentially
live another 10 to 15 years.

And despite the stereotype that aggressive chemotherapy should be limited
in older patients, Caldwell has had few side effects so far. In December
2006, she completed four rounds of chemotherapy with Adriamycin®
(doxorubicin) and Cytoxan® (cyclophosphamide), and is now receiving
Herceptin® (trastuzumab) and Taxol® (paclitaxel) with an aromatase
inhibitor.

She?s suffered some queasiness, but no vomiting. Despite becoming easily
winded, she was able to attend the Christmas gathering of her water
aerobics group. ?She?s kind of behaving like a 50-year-old,? says Dr.
Stewart, describing Caldwell?s response to treatment.

Treatment Complexities

Research into older patients? ability to withstand chemotherapy remains
limited. But one study published in 2003, involving 37 patients age 70 and
older, found the toxicity could be tolerated without a substantial
decline.

?Despite having side effects, [the patients] remained fairly functional
during chemotherapy,? says Dr. Extermann, one of the study?s researchers.
?They were having some difficulty doing their daily tasks, but they were
able to do them, in general, independently.?

The development of anti-nausea medications, such as Aloxi® (palonosetron)
and Emend® (aprepitant), as well as growth factors like Aranesp®
(darbepoetin alfa) and Neulasta® (pegfilgrastim) to boost depleted blood
cell counts, has enabled doctors to offer chemotherapy to older and older
patients, says Dr. Cohen.

Traditionally one of the biggest concerns about chemotherapy has been the
drugs? impact on bone marrow, he says. The ability of older patients to
produce red and white blood cells appears to be more limited when their
bodies are subject to the toxic stresses of chemotherapy. Newer targeted
therapies don?t appear to place such strain on the bone marrow, he says.
Still, there?s often a trade-off because the newer agents may have
potential effects on the heart or other organs.

Dr. Cohen and other physicians interviewed for this article most
frequently mentioned two types of chemotherapy they would use with more
caution, depending upon an older patient?s other health conditions.
Taxane-based chemotherapy, such as Taxol, can be associated with numbness
and tingling in the fingers and toes, a condition known as neuropathy that
can become severe. Anthracyclines, which include Adriamycin, can weaken
the heart muscle and might not be a good approach in a patient with a
history of heart disease (see ?Hazardous to Your Heart,? page 22). Other
drugs can be substituted, such as methotrexate and 5-FU or Doxil® for
Adriamycin. Other cancer drugs can also cause neuropathy, including
Velcade® (bortezomib) and cisplatin, and heart damage, such as Herceptin.

Surgery, not surprisingly, also carries its own challenges. Garrett Walsh,
MD, a surgeon at M.D. Anderson Cancer Center in Houston, is performing
surgery on people with lung cancer and other thoracic malignancies in
their 70s and early 80s, and sometimes even older. ?Age, by itself,
becomes less of an issue if the patient is otherwise healthy,? he says.

But he?s quick to add that you can?t underestimate the potential impact of
a major operation. Close monitoring during recovery is crucial, he says.
Older patients can become more easily dehydrated. They don?t necessarily
spike a temperature if they develop pneumonia. Moreover, if left
unaddressed, depression or inadequate pain control can discourage patients
from moving around and performing the breathing exercises vital to keeping
their lungs clear. ?Once you get a [medical] complication in an older
patient, their reserve is much less and a snowball effect can occur,? Dr.
Walsh says.

How Aggressive?

The practical reality for oncologists is that the patient sitting in their
office might not look anything like the older patient who qualified for a
clinical trial. Oncologists prefer to make treatment decisions based on
research studies. Where older patients are concerned, though, the evidence
can be slim at times.

?What we need now and are going to desperately need as the next couple of
decades go by,? Dr. Stewart says, ?are studies that provide solid evidence
of treatment benefit and toxicity in people in the older age ranges. As
time goes by, there are just going to be a lot of people who are over the
age of 85 and are very functional. When they get cancer, what are we going
to do??

Dr. Ershler points to the work of the Geriatric Oncology Consortium, a
group of researchers that?s trying to better understand the diverse needs
of older patients. (Drs. Ershler and Balducci sit on the consortium?s
scientific advisory board.) One of the consortium?s primary goals is to
include a variety of older cancer patients in research studies, including
those with other medical conditions besides cancer, says Robert Hauser,
PharmD, PhD, chief operating officer for the nonprofit group.

?What we need now and are going to desperately need as the next
couple of decades go by are studies that provide solid evidence of
treatment benefit and toxicity in people in the older age ranges.? ?James
Stewart, MD

Jean Caldwell is certainly not alone in fighting back aggressively against
cancer. In a 2003 study designed to assess attitudes toward chemotherapy
among 195 French and American cancer patients, both groups were
surprisingly open to undergoing strong chemotherapy: 70.5 percent of the
American patients and 77.8 percent of the French. Their average age: 77
years old.

__________________
Note: she's her2neu positive (the reference to Herceptin)

.