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