Today is the first day that I am sad about going through chemo-therapy-
Why
you may ask? Well, seeing my hair fall out was sad enough for one
day---but then I learned more about “chemo” brain. I happen to really
enjoy thinking and being clear minded. It was one of the things I
disliked so much about being “clinical depressed” not being able to
think clearly anymore. I am barely 60 and my breast cancer treatment, I
learned, is going to put me at risk for cognitive decline.
What
is increasing my chances for survival is Dose Dense treatment. Which
is 6 % more effective for long term survival than not doing it. And I am
doing it because I am allergic to a medicine in the first cocktail
(GIN) and I will get done sooner to get well and go on my cruise.
Initially I only wanted to do one dose of Dose Dense to get me done
sooner but when I was allergic to the first concoction, Dr. Gor changed
my cocktail,which is less effective than the first type of chemo-- we
agreed to do the reminder of treatments every 2 weeks.
So
I have suffered a major depression, so my brain is already at risk. My
father had dementia (PSP) at an early age in his 60’s. and I am obese
which puts my brain at risk for inflammation. And now I am having
chemotherapy which can cause cell death in the brain. And the chemo is
going to hit an already vulnerable brain.
So
the bottom line is I need to continue to loose weight and get active to
save my life and my brain. I will also likely consider discussing doing
a low dose of Donepezil when my chemo therapy treatment is complete.
Can't wait until my primary doctor gets a load of me for that request!
Lots of love,
Nancy
_______________________________________________________________________________________
· Progressive
supranuclear palsy (PSP) is a neurodegenerative brain disease that has
no known cause, treatment or cure. It affects nerve cells that control
walking, balance, mobility, vision, speech, and swallowing. Five to six
people per 100,000 will develop PSP.
Symptoms
begin, on average, when an individual is in the early 60's, but may
start as early as in the 40's. PSP is slightly more common in men than
women, but PSP has no known geographical, occupational or racial
preference.
PSP displays a wide range of symptoms including:
- Loss of balance.
- Changes in personality such as a loss of interest in ordinary, pleasurable activities or increased irritability.
- Weakness of eye movements, especially in the downward direction.
- Weakened movements of the mouth, tongue and throat.
- Slurred speech.
- Difficulty swallowing.
________________________________________________________________________________________
**
This often-unexpected side effect of cancer treatment leaves many
patients experiencing debilitating cognitive effects after chemotherapy.
Luckily, research and awareness are catching up.
By Beverly Burmeier
Ten
years ago Sharon Palmatory’s trouble remembering names and numbers
after chemotherapy treatment for breast cancer might have been brushed
aside as an insignificant occurrence, considering survival was the
primary concern. But today, thanks to early diagnosis and effective
treatment, more women survive breast cancer than ever before, and
quality-of-life issues like this are increasingly important.
“It’s
a definite medical condition,” says Dr. Christina Meyers, PhD, ABPP,
professor of neuropsychology in the Department of Neuro-Oncology at M.
D. Anderson Cancer Center in Houston, describing what has come to be
known as “chemo brain,” a lesser-known side effect of chemotherapy,
which can be just as serious as nausea, fatigue, and hair loss.
Thankfully, the condition—marked by a reduction in verbal or visual
memory, problems with attention and concentration, a reduction in the
speed of processing information, and visual or spatial abnormalities—is
the subject of several recent studies, as researchers seek clues to the
cause and the cure of this foggy mental condition.1
“Those
involved in long-term follow-up care for survivors are well aware of
their patients’ complaints that they cannot mentally function as well
after treatment as before,” says Dr. Mark Noble, professor of genetics
at the University of Rochester School of Medicine and Dentistry in
Rochester, New York. Too many people are affected to ignore the
syndrome—and not just breast cancer patients or women. Men experience
the foggy mental state associated with chemotherapy, too. As a result,
oncologists and nurses now make a better effort to provide patients with
information about the possibility of cognitive impairment occurring
either during or after active treatment.
Still,
many patients are surprised by the debilitating impact of the
condition. “I honestly didn’t know this would happen,” says Sharon, 39,
of Morgantown, West Virginia. “I was more concerned with fatigue and
taking care of my family.” But after her second chemotherapy treatment,
she went into a general fog for a week. “I couldn’t multitask,” she says
of the way the devastating side effect affected her demanding career as
a multimedia designer for government projects. “Losing my train of
thought was scary. And I couldn’t manage the household, remember names
and numbers, or balance my checkbook.”
Following
her fourth treatment, Sharon hit her lowest point, after which
improvement started slowly. “I still have a one-track mind, although
treatment ended several months ago,” she says. “I always have a pad of
paper to write things down.” She laughs that at her age she can’t
attribute these lapses to senior moments. “I rely on my husband to
remind me of appointments. The exit door to my garage is plastered with
notes.”
Recognizing the Condition
Doctors
used to think that impaired cognitive ability was related to other side
effects of chemotherapy. Anemia, fatigue, depression, and hormonal
shifts can all cause memory lapses and concentration difficulties. But
treating these conditions didn’t solve the problem for many patients.
And assessing the severity was difficult because there was no baseline
data of mental function before chemotherapy.2
“We
now know that chemo brain is a manifestation of central nervous system
toxicity that occurs in many cancer patients on active therapy and may
persist for 45 percent of patients after treatment is discontinued,”
says Dr. Meyers. Researchers also believe that some people have genes
that make cancer more responsive to treatment. This puts normal tissue
at risk for changes and makes them more susceptible to mental effects
from chemotherapy.
“We
know a fair deal about the damage done to the brain by radiation but
virtually nothing about the effects of chemotherapy,” says Dr. Noble.
“Imaging studies have shown clearly that high doses of chemotherapy
result in changes.” What isn’t known yet is which chemotherapy drugs
cause problems and how.
What Are the Newest Findings?
Fortunately
for breast cancer patients (the type of cancer most frequently studied
for cognitive impairment), chemo brain is currently a hot topic in the
lab. Researchers are discovering more about how the brain and the
nervous system are affected by toxic drugs used in chemotherapy. Still,
not everyone is affected, and scientists haven’t ferreted out enough
clues to determine who is at risk.
With
aggressive treatment the cure rate for Stage I cancers has grown as
high as 90 percent, yet not every woman with breast cancer needs
chemotherapy, although most get it, says S. David Nathanson, MD,
surgical oncologist at Henry Ford Health System in Detroit. That’s
significant because up to 25 percent of women who do receive it will be
affected by chemo brain—a statistic that complicates the decision about
who should get chemo.
Despite
advances in brain research during the past decade, the exact mechanisms
for cognitive impairment aren’t clearly understood, although it’s
recognized that standard chemotherapeutic agents can kill normal brain
cells. Dr. Noble’s research is attempting to understand how stem cells
function, with the hope of using them to prevent abnormal reactions or
to successfully repair damaged tissue.
“If
we can’t prevent the damage, can we repair it by stem cell or precursor
cell transplantation?” he asks. “It may be possible to use brain cell
transplantation to restore normal function, much as bone marrow
transplantation is used to restore normal function of the hematopoietic
system (organs and tissues involved in the production of blood)
following cancer treatment,” he says.
Dr.
Noble explains further: “In many ways, a cancer cell can be thought of
as the evil sibling of a stem cell. Understanding the features that
distinguish cancer cells from normal cells may enable cancer-specific
treatments to be developed without negatively affecting quality of life
for long-term survivors.” It may also help researchers develop a means
of selectively protecting normal cells from damage caused by radiation
and chemotherapy.
“The
only way to prevent or treat cognitive impairment associated with
cancer therapy is to understand why it occurs,” Dr. Noble adds. “One of
our concerns is to be able to better understand the reason for different
outcomes. Understanding why some people are resistant to these effects
will enable us to protect those who are more vulnerable, perhaps by
modifying treatment accordingly.”
Two
major studies are being conducted at the University of Sydney Cancer
Centre in Australia by oncologist Janette Vardy, MD. By studying brain
scans and blood tests from breast cancer patients (other research is
with colorectal cancer), her team has found that those who never
received chemotherapy, although they had breast cancer, had functional
MRI scans more like those of healthy control persons—and different from
those of patients who had received chemotherapy. “What we don’t know is
how those scanned differences will relate to how a person copes in
normal life,” Dr. Vardy says.
In
tests on the central nervous systems of experimental animals, Dr.
Noble’s team has found that during chemotherapy there is a long-lasting
reduction in cell division in the hippocampus of the brain, an action
believed necessary for normal memory function. “Our work shows that
there is damage to the insulation (myelin) that surrounds axons, with
eventual loss of the cells that produce the myelin. A lack of myelin
could also cause cognitive problems.”
Breakthroughs
may also result from research by Jame Abraham, MD, director of the
Comprehensive Breast Cancer Program at West Virginia University’s Mary
Babb Randolph Cancer Center. His team is one of the first to investigate
which specific changes in the brain lead to memory loss. Early research
shows differences in the white matter in the front part of the brain in
women who had received chemotherapy—differences that correlate with
their slower speed in processing information. “Our preliminary findings
suggest that chemotherapy may change the brain, and those changes affect
the patient’s cognitive skill,” Dr. Abraham says. West Virginia
University researchers also concluded that these changes do not appear
to be caused by depression or anxiety.3
For those affected, Dr. Abraham’s research regarding direct damage to
the brain from chemotherapy brings validation to their claims.
What’s a Patient to Do?
Sharon
Palmatory, a patient of Dr. Abraham’s, has suffered typical side
effects from her treatment. She explains: “I feel like I’m always two
paces behind—always struggling to keep up. When I lose my train of
thought, it’s hard to get it back.” The problem was severe enough for
her to request a transfer to slower-paced work with less aggressive
deadlines. (Dr. Meyers says 14 percent of affected people have to
discontinue work altogether.) “I couldn’t predict my reaction to
treatment on any given day,” says Sharon. Disorganization and
distractibility, when it occurred, affected her ability to perform at
her previous level.
Although
ongoing research is bringing physicians closer to developing targeted
treatments for preventing or treating chemo brain, patients like Sharon
are left to cope with various levels of cognitive impairment. Many will
recover normal or near-normal levels a year or two after chemotherapy,
but quality of life in the interim requires implementing strategies for
dealing with the mental haze. “Maintaining function is important,” says
Dr. Meyers. Sharon agrees, saying brain function is a “use it or lose
it” issue.
In
an instructional video provided to patients, Dr. Meyers outlines
several types of cognitive impairment that fall under the “chemo brain”
label:
- Reduced memory capability, both verbal and visual (“What’s your name again?”)
- Lack of focused attention or ability to process information (must read a paragraph several times to get the meaning)
- Learning new things takes longer (even though you’re still as smart as before)
- Multitasking is overwhelming (can’t talk on the phone and cook dinner at the same time)
- Easily distracted (“Why did I come in this room?”)
- Missing key points in discussion (“Please repeat what you just said”)
- Inability to find right word in conversations (You can’t just say “duh”)
- More effort required for usual tasks (daily activities leave you very fatigued)
Learning Adaptive Behaviors
“Although
it can be aggravating, having chemo brain is better than the
alternative,” reminds Dr. Meyers. After ruling out other possible causes
of memory problems, such as stress, depression, or medications, you can
help yourself cope by incorporating these suggestions into your daily
routine 4:
- Try relaxation training to help focus your attention.
- Write in a journal or diary to see what influences your memory problems.
- Set a routine or schedule that you follow consistently every day.
- Ride it out—settle in for the day and watch television or funny movies.
- Exercise; aerobic exercise helps your mood and increases alertness.
- Alter your work environment or expectations: simplify.
- Learn what your cognitive strengths are and capitalize on those. (What time of day is best for tackling tasks?)
- Compensate for weaknesses by using external memory aids (daily planner, notes, maps, and reminder phone calls).
- Discuss frustrations about slower moments with friends and family.
Regarding
software products that are marketed as memory-building tools, Dr.
Meyers says that repetitive mental exercises just don’t work. “You might
get better at the specific game, but the skills don’t carry over to
your life. For example, you might get better at Nintendo and still
forget your friend’s name.”
Help from the Pharmacy
At
this point no drugs have proved successful for combating the effects of
brain tissue damage. A small study conducted by Sadhna Kohli, research
assistant professor at University of Rochester, showed improvement in
memory, concentration, and learning for people taking Provigil®
(modafinil), a drug that stimulates the brain only as required and lasts
about 12 hours. Unlike Ritalin® (methylphenidate), which some patients
have tried, Provigil is nonaddictive.
It’s
also important that doctors assess and treat possible contributing
factors such as thyroid dysfunction, hormonal imbalance, or anemia. As
researchers come to better understand the mechanisms of chemo brain,
genetic factors may play a larger part in treatment plans.
Sharon
has found help close to home. Her mother is also being treated for
cancer. Staying active and having a sense of humor help, she says. “It’s
really important to be around people who understand you’ve gone through
treatment.”
Reference:
1
Tannock IF, Ahles TA, Ganz PA, Van Dam FS. Cognitive impairment
associated with chemotherapy for cancer: Report of a workshop. Journal
of Clinical Oncology. 2004;22(11):2233-39.
3
Abraham J, Haut MW, Moran MT, Filburn S, Lemiuex S, Kuwabara H.
Adjuvant chemotherapy for breast cancer: Effects on cerebral white
matter seen in diffusion tensor imaging. Clinical Breast Cancer.
2008;8(1):88-91.
________________________________________________________________________________________________________
Dose-dense chemo aids high-risk breast cancer patients
By: MITCHEL L. ZOLER, Oncology Practice Digital Network
Oct 8, 2014
Vitals
Key clinical point: A dose-dense chemotherapy regimen surpassed conventional dosing in high-risk breast-cancer patients.
Major finding: A dose-dense regimen produced 70% 5-year event-free survival, compared with a 62% rate with standard treatment.
Data source: AGO
ETC and GAIN, two multicenter, controlled phase III German trials with a
total of 2,141 patients receiving the dose-dense regimen.
Disclosures: The
two investigator-initiated trials received grant support from Amgen,
Bristol-Myers Squibb, Janssen-Cilag, and Roche. Dr. Thomssen has
received honoraria as a speaker for Amgen, Celgene, Pfizer, Roche,
Sanofi-Aventis, and TEVA.
Results confirm dose-dense advantages
The
results from these two German trials confirm that dose-dense
chemotherapy regimens are extremely effective for adjuvant treatment of
women with high-risk, node-positive early breast cancer of either the triple-negative type or with the luminal B phenotype.
U.S. researchers first reported similar findings in results published more than 10 years ago (J. Clin. Onc. 2003;21:1431-9),
although concerns existed about the relevance of the treatment received
by control patients in that study. Last year, Dr. Cognetti and other
Italian researchers reported a significant benefit from a dose-dense
regimen in a controlled study, but those results remain unpublished as
of now. Further confirmation by these two German studies now clearly
establishes dose-dense regimens as the standard of care for adjuvant
treatment of these types of breast cancer patients. The intensified,
dose-dense method is the preferred way to administer anthracyclines and
taxanes for adjuvant treatment in these high-risk patients.
|
Dr. Antonio Llombart-Cussac
|
In
some countries, such as in the United States and Germany, dose-dense
regimens are already standard, but not in other European countries
including Spain, Italy, and France. One reason is that the dose-dense
method costs more, as patients more often need support by treatment with
granulocyte colony stimulating factor, an agent that can increase
treatment costs three-fold. Some clinicians have also had lingering
concern about the potential of the dose-dense method to boost episodes
of secondary leukemia, So far, follow-up has shown no indication of
increased hematologic malignancies in the German or Italian patients,
but follow-up in these three trials has been brief, relative to the
10-20 years it could take for this adverse effect to appear. However,
the immediate efficacy benefit from dose-dense treatment is important
enough to justify using this approach even if we eventually see a small
increased rate of late leukemias.
Dr.
Antonio Llombart-Cussac is head of medical oncology at Arnau de
Vilanova Hospital in Valencia, Spain. He has received honoraria as a
speaker for or adviser to Celgene, GlaxoSmithKline, Roche, AstraZeneca,
Novartis, and Lilly. He made these comments as a designated discussant
for the reports and in an interview.
SAN
ANTONIO, Texas — After 10 years, dose-dense dose-intensified
chemotherapy continues to offer significantly better disease-free and
overall survival than standard chemotherapy for women with breast cancer
with axillary node involvement, according to a new study.
Ten-year
overall survival rates were higher in women treated with an intensive
dose-dense (IDD) regimen of epirubicin, paclitaxel, and cyclophosphamide
than in those treated with standard-dose epirubicin and
cyclophosphamide with sequential paclitaxel (69% vs 59%; P = .0007).
Volker
Moebus, MD, from the Academic Hospital of the Goethe University in
Frankfurt, Germany reported the study results here at the 35th Annual
San Antonio Breast Cancer Symposium.
Disease-free survival was also better with the IDD regimen (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63 - 0.87; P = .00014). This improvement occurred regardless of nodal, HER2, or estrogen-receptor status, Dr. Moebus said.
These findings extend those of a 5-year analysis of the data (J Clin Oncol.
2010;28:2874-2880), which showed better 5-year event-free survival
rates with IDD chemotherapy than with conventional chemotherapy (70% vs
62%; P < .001). Overall survival rates were also better with IDD chemotherapy (82% vs 77%; P = .0295).
IDD
"is a feasible regimen with manageable toxicity. We observed no
therapy-related deaths or long-term toxicity like congestive heart
failure or long-lasting peripheral neuropathy," Dr. Moebus said.
High Risk for Adverse Events
The
survival advantages came at a cost, however; 9 patients (1.3%) in the
IDD group developed myelodysplastic syndrome or acute myeloid leukemia,
compared with 2 (0.3%) in the standard-dose group. That had a couple of
clinicians who were not involved in the study worried.
Steven Vogl, MD, a private practitioner in the Bronx, New York, and a perennial gadfly and audience favorite
at cancer meetings, said that "in the United States...most of us think
that high-dose cyclophosphamide doesn't do any good, except in
generating patients for leukemia doctors."
He suggested that the benefit they saw with the IDD regimen might be attributable to more frequent dosing with paclitaxel.
Michaela
Higgins, MD, an instructor in medical oncology at the Massachusetts
General Hospital Cancer Center in Boston, agrees. "The improved benefit
seen in this study could be due to a number of factors," she told Medscape Medical News.
The
dose of cyclophosphamide used in the IDD regimen, which is much higher
than that used in the doxorubicin and cyclophosphamide regimen more
commonly delivered in the United States, might have been influential.
"It also may be a scheduling issue with [paclitaxel]. Several studies
have shown that [paclitaxel], given either weekly or 2-weekly, improves
outcomes over patients who were treated every 3 weeks," Dr. Higgins
said.
She noted that
the study reinforces the therapeutic benefits of more frequent dosing
with an anthracycline-based regimen in women at high risk (some of the
women in the study had as many as 10 lymph nodes involved). However, the
increased risk for myelodysplastic syndrome and leukemia and the high
rate of blood transfusions required in the IDD group (28% vs 13%)
mitigated the adoption of a similar regimen.
Dose-Dense Chemotherapy Benefits Persist for a Decade
