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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)
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
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
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
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
SIU 2007 - ECCO 2007 - SIOG 2007 - ASCO GU 2008Submitted to Critical Reviews in Hemato/oncology
Key predictors of health status& outcome which have been chosen.
1. Comorbidity2. Dependence status3. Nutritional status
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
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
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
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%
• 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
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
• 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
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
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
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
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
< 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
SR= Standard Regimen AR= Adapted Regimen
Italiano et al. Eur Urol 2009, 55: 1368-76
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.
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
• 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