“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”

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 problemP.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 morbidityPACE 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

Age

Percent of age group Living in a Nursing Home

20001990 2000

65 years and over

5.1% 4.5% 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 overClearwater, Fla.

108,787 23,357 21.5%

Cape Coral, Fla.

102,286 20,020 19.6

Honolulu, Hawaii2

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

Biology 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.

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

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

•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 follow-

up care

•Improving mental health and well-being

•Better pain control

UpToDate

What are the advantages of a CGA

•evaluation of functional status

•comorbid medical conditions,

•cognitive status,

•psychological state,

•social support,

• nutritional status

•review of the medication list

UpToDate

Typical CGA Includes the following:

Performance status

Definition

0Fully active; no performance restrictions

1Strenuous physical activity restricted; fully ambulatory and able to carry out light work

2Capable of all selfcare but unable to carry out any work activities. Up and about >50 percent of waking hours

3Capable of only limited selfcare; confined to bed or chair >50 percent of waking hours

4Completely disabled; cannot carry out any selfcare; totally confined to bed or chair

Clinical Geriatric Assessment 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 Comorbidities with high impact:

Cardiac arrest, CHF, COPD, CKD

Conditions requiring active tx; Angina, arrhythmia, MI, valvular d., TI DM, prior cancer

Comorbidities with moderate impact: Cardiac hx. (angina, MI, valvular d)

Conditions requiring active tx ETOH abuse, anemia, asthma, DVT, dpression, HTN,

HLP, liver d, mental illness, CVA or TIA

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

Medication Review : Number of medications Drug-drug interactions

Nutrition: Nutritional status and Nutritional risk Access to adequate nutrition

Treatment Approaches 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

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 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

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.

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

• Single agents chemotherapy could be the preferred

option :

- vinorelbine

- taxotere weekly

- capecitabine, infusional 5-FU

- gemcitabine

• In fragile patients single agents should be chosen

Advanced Breast Cancer in the Elderly

Prostate Cancer

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

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 Incidence: increases with age

- All age: 2.3/100,000

- Age60: 13.7/100,000

- Median age: 65-70 years old

Outcome of the treatment in elderly AML

Age < 60 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

Hiddemann, W et al, JCO 17(11) 1999

49% 34% 64% 15%

Major Prognostic Factors in AML For response:

Cytogenetics /molecular genetics

WBC count MDR phenotype Secondary AML Age

For relapse: Cytogenetics

/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

< 60 years >60 years

No. of Patients % No. of Patients %

Favorable 108 17 10 4

Intermediate 427 65 175 63

Unfavorable 123 18 94 33

Frequency of Karyotypes and Age :

Hiddemann, W et al, JCO 17(11) 1999

Elderly AML has high prevalence of MDR expression

MDR (multidrug resistance gene) 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.

Biological characteristics distinguishing secondary AML (t-AML and AML in the elderly) from true de novo AML

t-AML/t-MDS Elderly ‘de novo’ AML True ‘de novo’ AML

Age

Typical cytogenetic abnormality

Multilineage dysplasia/dyspoiesis

Multi drug resistant phenotype (MDR1)

Common in elderly Elderly common in younger

-5/del(5q), inv(3) t(3:21), -7/del(7q), 17/I 17q, complex, -20q, t(11q23), +8, +13.

+8, -5/del(5q), -7, del(7q), Complex

t(15:17), t(8:21), inv(16). Complex

>55 years 79% >55 years, 64% Uncommon

High frequency; > 70% High frequency; >70% 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

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.

Summary 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.

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.

Diagnosis

Unfavarable biology

(Cytogenetics, MDR, 2nd AML)

Yes No Contraindication against intensive(standard) therapy

Yes NoSupportive care onlyNew approaches

Intensive

(standard) therapy

Hiddemann, W et al, JCO 17(11) 1999

Decision making in Elder AML