Transcript Cancer_in_the_Elderly

“GERIATRICS MOVES TO
FOREFRONT IN ONCOLOGY”
 “ASCO takes a leadership role in educating
physicians, policymakers, and the public about
unique aspects of caring for older patients with
cancer”
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ASCO News Forum, Oct. 2006
A 99-year-old sprinter is one of the stars of the World Masters Games in
Australia.
Charles Booth carried the torch down an avenue of honour at the opening
ceremony in Melbourne.
The event has attracted more than 25,000 competitors aged between 24 and 99
from 97 countries.
The athletics track and field competition is to feature many competitors in their
80s.
They include former 400 metre world record holder Mike Johnston, who is 81.
Weightlifting competitors include 90-year-old Vladimir Younger, who aims to
beat relative youngsters to clinch gold.
The squash event is expected to be dominated by 87-year-old Vic Hunt, the
father of seven-times squash world champion Geoff Hunt.
The state of Victoria hopes to gain a ?44.74 million boost from the games,
which close on October 13.
CANCER IN THE ELDERLY
G. Luiken, MD 04/29/08
Noon Conference
Neoplasia in the Elderly: dimension of
the problem
P.Boyle-Joint NCI-EORTC Meeting 1990, Venice: Prediction for 2004
>60% of all tumors occur in persons > 65 years
>45% of all tumors occur in persons > 70 years
Predicting Surgical Outcomes
PACE
morbidity
PACE Item
Odds ratio
95% confidence
p
PS (2-4)
2.92
1.49
5.74
0.002
MMS (deficit)
1.53
0.92
2.54
0.140
ADL (dependent)
1.91
1.09
3.34
0.024
IADL (dependent)
2.12
1.38
3.25
0.001
GDS
1.82
0.98
3.38
0.057
BFI
2.27
1.39
3.71
0.001
ASA
1.15
0.65
2.03
0.636
Co-morbidity (3+)
1.89
0.98
3.64
0.058
Conclusions II Hospital stay
PACE variables associated with
prolonged hospital stay:
IADL (dependent)
x 1.64
BFI
x 5.08
No PACE variable correlated with
Mortality (observed mortality small)
Keller, SM; ASCO 2006
Percent of age group Living in
a Nursing Home
Age
65 years and
over
1990
5.1%
2000
4.5%
2000
1,557,800
65 to 74 years
1.4
1.1
210,159
75 to 84 years
6.1
4.7
574,908
85 years and
over
24.5
18.2
772,733
Place1
Total population
Population 65 and over
Percent 65 and over
Clearwater,
Fla.
108,787
23,357
21.5%
Cape
Coral, Fla.
102,286
20,020
19.6
Honolulu,
2
Hawaii
371,657
66,257
17.8
St.
Petersburg
, Fla.
248,232
43,173
17.4
Hollywood,
Fla.
139,357
24,159
17.3
Warren,
Mich.
138,247
23,871
17.3
Miami, Fla.
362,470
61,768
17.0
Livonia,
Mich.
100,545
16,988
16.9
Scottsdale,
Ariz.
202,705
33,884
16.7
Hialeah,
Fla.
226,419
37,679
16.6
It is estimated that by the year 2030, 20% of the
US population will be > 65 yr
 By 2020 the population will have increased 12%
but because of the aging of the population the
incidence of cancer in the overall population is
expected to increase by 60%
 The median age at which cancer occurs is 68
yrs
 More than 60% of all cancers are dx’d in
individuals >65 yr
 Pt.s with cancer who are >65 are 16x more
likely to die of their cancer
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Biology
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Telomere shortening and defective DNA repair
mechanisms are common to both aging and cancer and
may partially explain the higher incidence of cancer in the
elderly
The functional decline begins at age 30 and is est. to
occur at 1%/yr
Illness and medical interventions can change this
process
Renin, aldosterone, DHEA, sex hormones, T3 decr.
Insulin, NE, PTH, vasopressin and atrial naturietic peptide
increase
Decr. protein synthesis, loss of muscle strength and
mascle mass occur
Loss of connective tissue and thinning of the skin lead to
fragility of the skin, bruising, etc.
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Decreased GI motility, decreased hepatic and
renal function
Decreased CNS neurotransmitters
Immunologic dysregulation (multiple aspects
from increased Ig levels but decr. antibody
responses, decr. lymphocyte response to
mitogens, etc.)
Marrow reserve is decreased
Increased susceptibility to infections
Pharmacology
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Decreased volume of distribution Vd may result from a
decr. in total body water and hyponatremia
Lower levels of albumin lead to higher levels of free
drugs and increased toxicity
Anemia may also decr. volume of distribution Vd for
drugs like etoposide and anthracyclines that bind to
rbcs
Metabolism by P450 (CYP) enzymes in the liver is
decreased and drugs that require these enzymes for
metabolism or elimination should be used with caution
What are the advantages of a CGA
•Useful for predicting complications and side effects from
treatment
•Estimating survival
•Detecting problems not found by routine history and
physical examination in the initial evaluation
•Identifying and treating of new problems during the followup care
•Improving mental health and well-being
•Better pain control
UpToDate
Typical CGA Includes the following:
•evaluation of functional status
•comorbid medical conditions,
•cognitive status,
•psychological state,
•social support,
• nutritional status
•review of the medication list
Performanc
Definition
e status
0
Fully active; no performance
restrictions
1
Strenuous physical activity restricted;
fully ambulatory and able to carry out
light work
2
Capable of all selfcare but unable to
carry out any work activities. Up and
about >50 percent of waking hours
3
Capable of only limited selfcare;
confined to bed or chair >50 percent
of waking hours
4
Completely disabled; cannot carry out
any selfcare; totally confined to bed or
Clinical Geriatric Assessment
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Function:
 ADLs (eating, dressing,continence,
grooming, transfers, toilet function)
 Instrumental ADLs (IADL): (use of
transportation, $ management, shopping,
laundry, and household chores, telephone)
Comorbidity:
 Number and seriousness of comorbid
conditions i.e. cardiac, pulm., renal,
vascular, CNS (a low albumin level, Hb<12
have been associated with a decr. survival,
and anemia has been linked to incr. risk for
dementia, CHF and cardiac death)
Impact of Comorbidities on Survival
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Comorbidities with high impact:
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Conditions requiring active tx;
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Angina, arrhythmia, MI, valvular d., TI DM, prior cancer
Comorbidities with moderate impact:
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Cardiac arrest, CHF, COPD, CKD
Cardiac hx. (angina, MI, valvular d)
Conditions requiring active tx
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ETOH abuse, anemia, asthma, DVT, dpression, HTN,
HLP, liver d, mental illness, CVA or TIA
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Geriatric Syndromes:
• Dementia (30-40% of pt.s >80)
• Depression
• Delirium
• Falls (1 or more/month)
• Osteoporosis (spontaneous fractures)
• Neglect and abuse
• FTT
Socioeconomic Issues
• Living conditions
• Presence and capability of caregiver
• Income
• Access to transportation
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Medication Review :
 Number of medications
 Drug-drug interactions
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Nutrition:
 Nutritional status and
 Nutritional risk
 Access to adequate nutrition
Treatment Approaches
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Pain is consistently undertreated in the elderly (esp. in
women and underserved minorities)
Pt.s may have an increased pain threshold
Identifying the source and severity of pain may be
complicated by confusion and dementia and comorbid
conditions may complicate or magnify pain issues
Persistent pain may contribute to depression and
depression may amplify the pain (necessitating treating
both pain and depression)
Older patients may be very sensitive to opioids and their
use may aggravate cognitive function
Delirium and agitation are side effects of opioids
Sedatives may incr. agitation
Chemotherapy and Radiation Therapy
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Oral cytotoxics are adequately absorbed
Renally excreted drugs (MTX, Bleo, CDDP, Cytoxan,
Ifos) should be given with caution
Peripheral neuropathy may occur more frequently
(vincristine, vinblastine, paclitaxel, oxaliplatin,
thalidomide, revlimid,)
Cardiotoxicity (anthracyclines, i.e. Adria, DNR,
Mitoxantrone, Epirubicin)
Mucositis is more common; 5FU,
Combined chemo/XRT is more toxic in the elderly
Special Considerations in Common
Malignant Diseases
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In the absence of substantial functional decline,
cancers in the elderly should be treated in the same
manner as in the young
The benefits for adjuvant chemotherapy for breast
and colon cancer in the elderly are similar to those
seen in younger patients
Chemotherapy may improve survival and QOL for
elderly pts with extensive NSCLCa
Colon Cancer in the Elderly
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More than 2/3 of all colon cancers develop in pt.s
over 65
Lesions are more common on the R and anemia is
more common than pain
Surgery for possible cure or for palliation is
appropriate
Because of the mortality and morbidity associated
with emergency surgery in pt.s >70, palliative
surgery should be considered even in advanced d.
(to prevent obstr.)
Adjuvant chemo yields the same survival benefit
for pt.s >70 as for those younger
Palliative chemo for adv. d. should be offered for
the elderly as well as for the young
Screening colonoscopy q 10 yr up to age 85
Lung Cancer in the Elderly
Adjuvant Therapy for Lung
Cancer in the Elderly
ADJUVANT THERAPY FOR
BREAST CANCER IN THE
ELDERLY
Hurria, A. ASCO Education Book 2006
Breast cancer is a disease of older women, with more than half of
deaths from breast cancer occurring in women age 65 and older.
The majority of breast cancers in older women are hormone
receptor positive, and therefore, hormone therapy is the standard
of care to decrease the risk of relapse and mortality from breast
cancer. Chemotherapy provides an additional benefit, but its risks
and benefits need to be considered on an individualized basis,
taking into account the tumor characteristics, the magnitude of
benefit, the expected risks, and the patient's preference. For those
patients with clinical stage I estrogen-receptor--positive tumors
treated with adjuvant hormone therapy, the omission of radiation
following lumpectomy is associated with a small increased risk of
local recurrence, but no difference in overall survival with 5 years
of follow-up. This is consistent with the general principle that
competing forces of mortality become increasingly important in
making treatment decisions in older patients.
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Almost 50% of breast cancers develop in women >65
13% develop in women >80 yr (however 25% of breast
cancer deaths occur in this age)
In subset analyses, older women do derive benefit from both
chemo and hormonal tx
Tumors seem to be somewhat less aggressive as women age
Resection of the primary and tx. with an AI or Tamoxifen may
be appropriate for women with small ER+ breast cancer and a
finite life expectancy
The guidelines for adjuvant chemotherapy are the same as for
younger women (in the absence of severe comorbidities)
The American Geriatrics Society recommends annual
screening MMG for women up to the age of 85 years if their
life expectancy exceeds 3 years
Advanced Breast Cancer in the Elderly
• Single agents chemotherapy could be the preferred
option :
- vinorelbine
- taxotere weekly
- capecitabine, infusional 5-FU
- gemcitabine
• In fragile patients single agents should be chosen
Prostate Cancer
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Predominantly affects older men (>90% of deaths occur in men >
65)
A large Scandinavian trial (SPCG) compared watchful waiting to
radical prostectomy (med. age 65. at 6 yrs f/u overall survival was =
between the 2 groups, however those who had had surg. were less
likely to die of prostate cancer)
If the pt. has mult. other comorbid conditions, watchful waiting may
be very appropriate
Surgery is indicated if obstr. sx’s are present
Occult prostate cancer can be found in up to 39% of men 70-79 at
autopsy and in 43% of men >80
Non-Hodgkins Lymphoma
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More than ½ of cases are dx’d in pt.s >60
Age is one of the poor risk factors for NHL although the
prognosis is favorable for all pt.s with stage I & II d.
In pt.s tx’d with CHOP, neutropenia FN is more common
in those >60
In pts. 60-80 with DLCL, CHOP-R increases the CR rate
(76 vs 63%) 2 yr. DFS, and overall survival rate
compared to CHOP
Coiffier, et al; NEJM; Volume 346:235-242 Jan 2002
Management of AML in
Elderly
Minxiang Gu, MD
November 1,2002
Acute Myeloid Leukemia
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Incidence:
- All age:
2.3/100,000
- Age60:
13.7/100,000
- Median age:
65-70 years
old
increases with age
Outcome of the treatment in elderly
AML
 60
Age
< 60
CR
70 %
45-55 %
MS
11 months
6-9 months
5 year survival
35-40 %
5-8 %
Response Rate and Mortality of
Induction Chemotherapy
49%
34%
64%
15%
Hiddemann, W et al, JCO 17(11) 1999
Major Prognostic Factors in AML
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For response:
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For relapse:
 Cytogenetics
 Cytogenetics
/molecular genetics
 WBC count
 MDR phenotype
 Secondary AML
 Age
/molecular genetics
 Time towards
completed response
 WBC count
 flt-3 mutations
 Autonomous
proliferation
 Secondary AML
 Age
Karyotype and the Prognosis
Elderly AML have higher incidences of unfavorable
chromosomal abnormalities and lower incidences of
favorable chromosomal abnormalities
Frequency of Karyotypes and Age :
< 60 years
No. of Patients
>60 years
%
No. of Patients
108
17
10
4
Intermediate 427
65
175
63
Unfavorable 123
18
94
33
Favorable
%
Hiddemann, W et al, JCO 17(11) 1999
Elderly AML has high prevalence of MDR
expression
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MDR (multidrug resistance gene)
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P-glycoprotein, 170 kDa, chromosome 7
ATP-dependent transport protein
Binds to a variety of substrates (anthracycline,
epipodophylotixin)
Reversal agents: calcium channel blocker
(verapamile), Cyclosporine A, Quinidine, PSC 833.
Expressed in 70% of AML patients > 60 and only 37%
in patients <60.
Correlated to lower CR, short remission duration and
poor survival.
Elderly AML and Secondary AML
Higher incidence of secondary AML
in elderly.
 The de novo AML in elderly is
cytogeneticly similar to secondary
AML.
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Biological characteristics distinguishing secondary AML (tAML and AML in the elderly) from true de novo AML
t-AML/t-MDS
Age
Common in elderly
Typical
cytogenetic
abnormality
-5/del(5q), inv(3)
t(3:21), -7/del(7q),
17/I 17q,
complex, -20q,
t(11q23), +8, +13.
Multilineage
dysplasia/dys
poiesis
>55 years 79%
Multi drug
resistant
phenotype
(MDR1)
Elderly ‘de novo’ AML
High frequency; > 70%
Elderly
+8, -5/del(5q), -7,
del(7q), Complex
>55 years, 64%
High frequency; >70%
True ‘de novo’ AML
common in younger
t(15:17), t(8:21),
inv(16).
Complex
Uncommon
Low frequency;
MDR1 usually absent
in t(15:17), inv(16)
and t(8:21)
Dann.E J, et al Best Practice & Research Clinical Haematology, 14(1) 2001
Summary
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Higher incidence of unfavorable
cytogenetics.
Higher incidence of MDR expression.
Increased prevalence of antecedent
hematological disease.
Limited proliferative capacity of hemapoietic
stem cell.
Comorbility and different metabolism cause
high treatment related mortality.
Should we treat elderly AML
with intensive
chemotherapy?
- Supportive Care verses Anti-leukemia
Chemotherapy
Conclusion
No standard consolidation regimen for
elderly AML.
 May benefit from standard dose or
lower dose Ara-C therapy.
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Summary
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Elderly AML represent a discrete population in
terms of the biology of the disease, prognosis
and treatment-related complications. It should be
managed differently from the younger age
population.
The cytogenetics, MDR expression, secondary
AML, performance status and comorbility play
important roles in the clinical decision making.
If there is no contraindication, the standard
induction chemotherapy is favored to achieve
better CR rate and long-term survival.
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Hematopoietic growth factors can be used safely
to shorten the duration of critical neutropenia, but
not improve CR rate and overall survival.
The standard regimen for postremission therapy
has not been established. Standard or low dose
of Ara-C can be considered.
Aggressive chemotherapy in relapsed AML only
show survival benefit in small group of patients.
Mylotarg shows benefit in this setting.
Decision making in Elder AML
Diagnosis
Unfavarable biology
(Cytogenetics, MDR, 2nd AML)
Yes
Supportive care only
New approaches
No
Contraindication against
intensive(standard) therapy
Yes
No
Intensive
(standard) therapy
Hiddemann, W et al, JCO 17(11) 1999