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Prostate cancer: assessment of senior adult patients for
chemotherapy – SIOG guidelines
Jean-Pierre Droz, MD, PhD.Professor Emeritus of Medical Oncology
Claude-Bernard-Lyon University Consultant, Centre Léon-Bérard,
Lyon, France
SIOG meeting 16-17 october 2009 - Berlin (Germany)
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05
1015202530354045
35-44 45-54 55-64 65-74 75-84 85+
Perc
enta
ge o
f men
Age, years
0.1% 1.5%
7%
20%
41.5%
30%
Age distribution of men with prostate cancer at diagnosis & death in US - SEER (2000-2005)
0.6%
9%
27%
35%
21%
4.5%
At death of prostate cancerAt diagnosis
Most deaths due to prostate cancer occur in senior adults
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Walter LC et al. JAMA 2001, 285, 2750-2756
Top 25th percentile
Lowest 25th percentile
50th percentile
Healthy
Vulnerable(median)
Frail
18
14.2
10.8
7.9
5.84.3
12.4
9.3
6.7
4.73.2
2.3
6.74.9
3.32.2 1.5 1
0
5
10
15
20
25
70 years 75 years 80 years 85 years 90 years 95 years
Life
exp
ecta
ncy,
yea
rsLife expectancy in senior adults: a large
variability reflecting health status variability
Need for healthstatus evaluation
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An approach to the heterogeneity of health status:
Philip Wood’s Sequence(ICIDH-WHO 1980)
• Impairment (organ/function)• Disability (activity/ person)• Handicap (social life)
Disease
Dependency
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Survival depends of individualhealth status
Rockwood K et al. Lancet 1999, 353, 205-206
Pro
porti
on s
urvi
ving
Time to death (months)
IndependentIncontinence onlyVulnerable*Frail**
Independent
frail
vulnerable Vulnerable and frail senior adults are the majority and are at
death risk !
*Vulnerable: need for assistance in ≥ 1 (or ≥ 2 if incontinence) activities of mobility or daily livingor cognitive impairment without dementia or bowel + urinary incontinence
**Frail: need for assistance in ≥ 2 (or ≥ 3 if incontinence) activities of mobility or daily livingor dementia or bowel + urinary incontinence
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SIU 2007 - ECCO 2007 - SIOG 2007 - ASCO GU 2008Submitted to Critical Reviews in Hemato/oncology
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Key predictors of health status& outcome which have been chosen.
1. Comorbidity2. Dependence status3. Nutritional status
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Assigned weight Condition1 (each) Myocardial infarction
Congestive heart failurePeripheral vascular diseaseCerebrovascular disease (except hemiplegia)DementiaChronic obstructive pulmonary diseaseConnective tissue diseaseUlcer diseaseMild liver diseaseDiabetes (without complications)
2 (each) HemiplegiaModerate or severe renal diseaseDiabetes with end-stage organ damage2nd solid tumour (non metastatic)LeukaemiaLymphoma, multiple myeloma…
3 Moderate or severe liver disease6 (each) 2nd metastatic solid tumor
AIDS
Comorbidities: Charlson comorbidity index
Total score: [0–30]
Charlson et al. J Chronic Dis 1987;40:373-83
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Evaluation of dependence statusin senior adults
IADL1 ADL2
1IADL: simplified Instrumental Activities of Daily Living (Lawton, Gerontologist 1969, 9: 179)2ADL: index of independence in Activities of Daily Living (Katz, JAMA 1963, 185: 914)
One abnormality is significant
Get place at walking distanceUse telephoneTake medicationManage money
TransferContinenceGoing to toiletBathingDressingFeeding
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Survival depends of dependence status
Rockwood K et al. Lancet 1999, 353, 205-206
Pro
porti
on s
urvi
ving
Time to death (months)
IndependentIncontinence only1 ADL≥ 2 ADL
Independent
≥ 2 ADL
1 ADL
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Malnutrition increases the risk of death
All patients Patients withcongestive heart failure
Mor
talit
y, %
No malnutrition
Malnutrition
No malnutrition
Malnutrition
Months after admission Months after admission
205 patients with cancer aged 75 years
Cederholm T et al. Am. J. Med 1995, 98, 67-73
Measure of weight loss during the last three months:no malnutrition: < 5%at risk: 5 to 10%severe malnutrition: >10%
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• Treatment decisions should be based on evaluation of patient “health status”:– “Fit” or healthy senior adults should receive
the same treatment as younger patients– “Vulnerable” patients (who have reversible
impairment) should receive standard treatment after readaptation.
– “Frail” patients (who have non-reversible impairment) should receive adapted treatment
– “Too sick” patients are candidates for palliative treatment
SIOG proposed recommendations
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Hormonal treatment
• Hormonal treatment (LH-RH agonists) isfirst-line treatment in metastatichormone-sensitive prostate cancer
• It slows progression and reduces the riskof serious complications
• However, care is needed in senior adultsdue to increased risk of fracture, diabetesand myocardial infarction
Advanced prostate cancerspecial considerations for senior adults
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• Androgen deprivation induces bone loss• Baseline evaluation: bone mineral density
+ dosage Ca & Vitamine D3• Supplémentation with calcium & vitamine D:
– Cholécalciférol (vit D3) 100.000 U/ 1 à 3 months– Calcium : 500 mg à 1g / d. (serum Ca control)
• Previous ostéoporosis : biphosphonates– Dose is debatable– Take care of toxicity (maxillary necrosis)
Hormonal treatment
Advanced prostate cancerSpecial considerations for senior adults
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In castration-resistant prostate cancer, docetaxel shows a similar benefit in young
and senior adults (TAX 327)
0.5 0.7 0.9 1.0 1.1 1.3 1.5
All patientsAge ≤ 68 yearsAge ≥ 69 years
PSA <115 ng/mLPSA ≥115 ng/mL
No painPainKPS ≤80%KPS ≥90%FACT-P <109FACT-P ≥109
FavorsDocetaxel q3w
FavorsMitoxantrone
Berthold D et al. J. Clin. Oncol. 2008; 26:242-45
No visceral diseaseVisceral disease
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Fossa et al. Eur Urol 2007, 52: 1691-99
109 patients with HRPC randomizedto docetaxel (30 mg/m2 weekly 5/6 weeks) + prednisolone
or prednisolone aloneNo cross-over – Median age 70 years
Weekly docetaxel in CRPC
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Docetaxel weekly+ prednisolone Prednisolone
Progression-free survivalmedian [95% CI]
11 mo[5.8-16.2]
4 mo[2.4-5.6]
Overall survivalmedian [95% CI]
27 mo[19.8-34.2]
18 mo[15.2-20.8]
Survival rate (%)- 1-year- 2-year
82%61%
67%29%
12-wk QoL improvement- Physical function- Pain- Fatigue- Nausea/vomiting- Global quality of life
27%52%38%17%27%
3%16%29%8%16%
Weekly docetaxel improves survival
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Beer et al.Clinical prostate cancer 2003, 2: 167-172
Pooled analysis of two phase II clinical studiesof weekly docetaxel (36mg/m2 for 6/8 weeks)
in men with metastatic HRPC
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< 70 years(n=34)
≥ 70 years(n=52)
ECOG performance0123
17.6%55.9%23.5%2.9%
23.1%50%
26.9%0%
Overall survivalmedian [95% CI]
45 weeks[36-54]
33 weeks[13-54]
PSA response rate[95% CI]
40%23%-57%
47%33%-61%
Measurable disease progression rate [95% CI]
33%[0-66%]
29%[0-65%]
No significant differences for all parameters
Weekly docetaxel has the same activity and the same toxicity < 70 and ≥ 70 years
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SR= Standard Regimen AR= Adapted Regimen
Italiano et al. Eur Urol 2009, 55: 1368-76
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Advanced prostate cancerSpecial considerations for senior adults
• In CRPC, chemotherapy with docetaxel(75 mg/m2 q3w) is the standard and showsthe same efficacy in healthy senior adults asin younger patients.
• The tolerability of docetaxel q3w has not been specifically studied in vulnerable and frail senioradults. The place of weekly docetaxel in thissetting should be further evaluated.
• Palliative treatments include palliative surgery, radiopharmaceutics, radiotherapy, medicaltreatments for pain and symptoms.
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Adapted (weekly?)chemotherapy
Standardchemotherapy
Symptomatictreatment
Standardchemotherapy
Hormonal treatment (first and second lines, anti-androgen withdrawal, biphosphonates)
Life expectancy evaluation
Readaptation
Group 1(Healthy)
Group 2(Vulnerable, i.e.
reversible problem)
Group 3 (Frail, i.e.
non-reversible problem)
Group 4(Terminal illness)
• Comorbidity (CISR-G): grade 0,1 or 2
• Independent in IADL*• No malnutrition
• Comorbidity (CISR-G): at least one grade 3
• Dependent in ≥1 IADL*• At risk of malnutrition
• Comorbidity (CISR-G): several grade 3 or at least one grade 4
• Dependency: at least 1 ADL impaired
• Cognitive impairment • Severe malnutrition
• Terminal• Bedridden • Major comorbidities• Cognitive impairment
Guideline: advanced prostate cancer
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• Objective:– To assess the impact of health status on the management
of metastatic castration refractory prostate cancer (CRPC)in senior adults (≥70 years)
• Design: – 6-month, prospective, international, multicenter, disease
registry
• Patients:– 500 patients aged 70+ with metastatic CRPC in 9 countries
(France, Germany, Spain, Turkey, Greece, Brasil, Tunisia, Mexico, Korea)
• Timelines: – Start November 2009– End: December 2010
MATuRITY: a prospective survey of senior adults with CRPC