Co-Morbidities: influence on treatment

Frail and elderly patientsCo-morbidities: influence on treatment

D. Schrijvers, MD, PhD

Ziekenhuisnetwerk Antwerpen-Middelheim

Antwerp, Belgium

• Changing demographics – Increase in number of elderly

• 2030: 20% of the population > 65 years (USA)• Cancer: disease of the elderly

– 60% of new cancer cases in patients > 65 years– 70% of cancer mortality in patients > 65 years

• Prostate – Incidence: 75% in patients > 65 years– Mortality: 92% in patients > 65 years

• Breast – Incidence: 47% in patients > 65 years– Mortality: 58% in patients > 65 years

Cancer burden will increase in elderly

Cancer epidemiologyCancer burden

• Age• Geriatric syndromes

– Malnutrition/urinary incontinence/visual and hearing impairment/gait, motility and balance

– Polypharmacy – Depressive disorders – Frailty– Age-related decrease in functioning

• Physical• Cognitive

• Disabilities: limitation in functional status• Self-reliance in daily living

• Co-morbid conditions• Cardiovascular disease• Respiratory disease• Endocrine disease

– 80% of patients > 65 years 1 or more chronic disease

Cancer epidemiologyProblems in cancer patients

Koroukian 2006

Problems in elderly cancer patientsDistribution of co-morbidity, disability, and

geriatric syndromes

Breast cancer (n= 952, mean age 76.6, 26.4%)

Prostate cancer(n=324, mean age 79, 3, 12%)

Importance of co-morbidity

Importance of co-morbidityLife expectancy in relation to health status

Age (years) Life expectancy (years) (women/men)

Healthy Average Sick

65 20.0/15.9 18.5/14.9 9.7/8.5

70 15.8/12.5 14.8/11.8 8.6/7.4

75 12.1/9.5 11.5/9.1 7.3/6.2

80 8.8/7.0 8.4/6.8 5.9/4.5

85 6.1/5.0 5.9/4.9 4.5/3.8

Extermann 2005

Holmes 2003

Importance of co-morbidityPrevalence and age trends for selected co-morbidities

Importance of co-morbidityCo-morbidity in relation to age in cancer patients

Co-morbidity Age (years) (% of population)

50-59 60-74 >75

None 55 35 26

Previous cancer 7 12 16

COPD 8 15 16

Heart diseases 6 15 19

Vascular disease 2 5 6

Hypertension 9 16 16

CVA/hemiplegia 1 4 6

Diabetes mellitus 4 8 10

Coeberg 1999

Importance of co-morbidityCo-morbidity burden in cancer patients

Study Miles Yanick

Cancer type Lung ColorectalMedian number of co-morbidities 2 3.6-4.2

Cardiovascular (%) 60 63Respiratory (%) 35 16Gastro-intestinal (%) 32 22Genito-urinary (%) 27Osteoarticular (%) 21 18Diabetes (%) 11Psycho-neuro (%) 5 Hematological (%) 37

Evaluation of co-morbidity

Evaluation of co-morbidityCharlson co-morbidity index

Index 1Chronic obstructive pulmonary diseases

Cardiovascular diseases: myocardial infarction, cardiac decompensation, angina pectoris, peripheral arterial disease, intermittent claudication, abdominal aneurysm

Cerebrovascular diseases: cerebrovascular accident

Hypertension (medically treated)

Diabetes mellitus

Auto-immune diseasePeptic ulcerationDementiaLiver function disturbances

Charlson 1987

Index 2

Hemiplegia

Kidney function disturbances (moderate/severe)

Diabetes mellitus with terminal organ damage

Tumours: solid tumours, leukemia, lymphoma

Index 3

Liver function disturbances (moderate/severe)

Index 6

AIDS

Metastatic cancer

Evaluation of co-morbidityOther scales

• Charlson Comorbidity index adapted to the International Classification of Diseases (ICD-9)

• Chronic Disease Score: co-morbidity based on current medication use

• List of co-morbid condition by the National Institute or Aging and National Cancer Institute

• Geriatric assessment scale

Co-morbidity and prognosis

Co-morbidity and prognosisInfluence on survival

Charlson Index score 1-year survival rate (%)

0 88

1-2 74

3-4 48

> 5 15

Charlson 1987

Satariano et. al. 1994

3-year mortality in 936 patients in relation to stage and co-morbidity

Co-morbidity and prognosisInfluence on survival in breast cancer patients

Co-morbidity and prognosisInfluence on survival in cancer patients

Coebergh 2004

Type co-morbidity 5-year survival

NSCLC Breast Colon Rectum

Age (years) > 70 > 70 <80 > 80 <80 >80

Loc* Non-loc**

None 41 21 67 51 40 49 37

Cardiovascular 41 31 42 38 23 28 21

COPD 21 23 51 37 31 36 29

Diabetes mellitus 19 10 41 46 32 37 20

Previous cancer 25 18 49 39 36 49 22

*: 3-year survival; **: 1-year survival

Co-morbidity and prognosisInfluence on survival in cancer patients

Read 2004

Co-morbidity and treatment

Co-morbidity and treatmentSurgery

ASA classificationClass I: The patient has no organic, physiologic, biochemical, or psychiatric disturbance. The

pathologic process for which the operation is to be performed is localized and does not entail a systemic disturbance.

Class II: Mild to moderate systemic disturbances caused by the conditon to be surgically treated or the pathophysiologic processes. The extremes of age are included here, the neonate or the

octogenarian, even though no discernible systemic disease is present. Extreme obesity and chronic bronchitis also are included in this category.

Class III: Severe systemic disturbance or disease from whatever cause, even though it may not

be possible to firmly define the degree of disability.

Class IV: Indicative of the patient with severe systemic disorders that are already life-threatening and not always correctable by an operation.

Class V: The moribund patient who has little chance of survival but who has submitted to operation in desperation. Most of these patients require an operation as a resuscitative measure with little, if any, anesthesia.

Emergency Operation (E): Any patient in classes I through V who is operated on as an emergency is considered to be in poor physical condition. The letter E is placed beside the numerical classification.


Goldman Criteria for Predicting Postoperative Cardiac Complications

Criteria Point Value

1. S3 gallop or jugular-vein distention on preoperative examination 11

2. Myocardial infarction in the preceding 6 months 10

3. Rhythm other than sinus, or premature atrial contractions on 7

preoperative electrocardiogram

4. >5 premature ventricular contractions/min documented at any 7

time before operation

5. Age >70 years 5

6. Emergency operation 4

7. Important valvular aortic stenosis 3

8. Intraperitoneal, intrathoracic, or aortic operation 3

9. Poor general medical condition* 33

*: P 2 < 60 or P 2 > 50 mm Hg, K < 3.0 or Cr > 3.0 mg/dL, abnormal SGOT, signs of chronic liver disease, or

patient bed ridden from non-cardiac causes


Goldman Criteria for Predicting Postoperative Cardiac Complications

Class Point Total No or Only Minor Complication Life-Threatening Complication Cardiac

Death

I 0–5 99% 0.7% 0.2%

II 6–12 93% 5% 2%

III 13–25 86% 11% 2%

IV ≥26 22% 22% 56%


Possum

Copeland, 2002

Co-morbidity and treatmentChemotherapy

Agent Special Considerations in relation to co-morbidity

Anthracyclines Avoid use of doxorubicin in patients with an EF <50%.

Cyclophosphamide Elimination decreased in patients with impaired renal function

Methotrexate Dose adjustments based on renal function

Patients with pleural effusions and ascites at risk for prolonged drug elimination and toxicity

Fluorouracil Fluorouracil-induced cardiac toxicity

Vinca alkaloids Monitor carefully for neuropathy

Taxanes Hepatic impairment increases toxicity

Trastuzumab Cardiotoxicity

Co-morbidity and treatmentDrug- drug interactions

Agent Special Considerations in relation to co-medication

Capecitabine Increased effect of warfarin, decreased metabolisation of phenytoin due to interference of CYP2C9

Fluorouracil Activation inhibited by allopurinolMethotrexate Increased toxicity with non-steroidal anti-inflammatory drugs,

sulfonamides, trimethoprimCytarabine Elimination decreased by nephrotoxic drugs

Carboplatin Decreases phenytoin levelCisplatin Other nephrotoxic drugs, decreases phenytoin levelCyclophosphamide Increased effect of warfarine, decreases digoxin level, increased

metabolisation by cytochrome P450 inducersProcarbazine Increased adverse effects by ethanol, sympatohomimetics, tricyclic

anti-depressants, opiates, antihypertensive drugsTemozolomide Clearance reduced by valproic acid

Inducers of cytochrome P450: e.g. dexamethasone, carbamazepine, rifampicin, phenobarbital, phenytoin. Substrates of P450: e.g. simvastatin, cyclosporine, triazolobenzodiazepines, carbamazepine, dihydropyridine calcium channel blockers, fentanyl, warfarin.



Docetaxel Metabolisation changed by drugs influencing cytochrome P450 3A4Paclitaxel Metabolisation changed by drugs influencing cytochrome P450 3A4,

clearance decreased when platinum coumpounds are given beforeVinblastine Metabolisation changed by drugs influencing cytochrome P450 3A4,

decreases phenytoin levelVincristine Metabolisation changed by drugs influencing cytochrome P450 3A4,

decreases digoxin and phenytoin levelVinorelbine Metabolisation changed by drugs influencing cytochrome P450 3A4

Etoposide Increases effect of warfarineIrinotecan Metabolisation changed by drugs influencing cytochrome P450 3A4,

increases effect of warfarine

Inducers of cytochrome P450: e.g. dexamethasone, carbamazepine, rifampicin, phenobarbital, phenytoin. Substrates of P450: e.g. simvastatin, cyclosporine, triazolobenzodiazepines, carbamazepine, dihydropyridine calcium channel blockers, fentanyl, warfarin



Tamoxifen Potentiates effect of warfarin

Exemestane Metabolisation changed by drugs influencing cytochrome P450 3A4

Inducers of cytochrome P450: e.g. dexamethasone, carbamazepine, rifampicin, phenobarbital, phenytoin. Substrates of P450: e.g. simvastatin, cyclosporine, triazolobenzodiazepines, carbamazepine, dihydropyridine calcium channel blockers, fentanyl, warfarin

Co-morbidity in cancer patientsFlow sheet

Frailty• Disability• > 3 co-morbidities• Geriatric syndrome

Life expectancy based on• Age• Co-morbidity

Life expectancy > cancer survival Life expectancy < cancer survival

Contra-indications anti-cancer treatment

Risk and benefitsanti-cancer treatmentIADLNutritional statusSocial structure

Risks < Benefits Risks > Benefits

Anti-cancer treatment

Follow up Palliative care

Cancer influences QoLNo influence of cancer on QoL

- +

- +

Co-morbidity in cancer patientsConclusions

• Cancer patients should receive optimal anti-cancer treatment in relation to – Life expectancy – Improvement of quality of life

• Treatment should be adapted to – Co-morbidity status– Disabilities– Geriatric syndromes– Co-medication

Co-morbidity in cancer patientsFuture questions

• Co-morbidity assessment• Patient selection for anti-cancer treatment based on co-

morbidities, disabilities and geriatric syndromes• Predictive models for side effects

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Co-Morbidities: influence on treatment