Treatment of Special Populations:Elderly and PS2 patients

Cattedra di Oncologia Medica e U.S. di OncoGeriatria,Policlinico Universitario di Palermo

Dir. :Prof.I.Carrecaonccar@unipa.it

Highlights in the Management of NSCL Cancer Rome June,13-14 08 –MSO

Azienda Ospedaliera UniversitariaPoliclinico Paolo Giacconedell’Università degli Studi di Palermo

Young old: 65-74 years of ageYoung old: 65-74 years of age

Older old: 75-84 years of ageOlder old: 75-84 years of age

Oldest old: over 85 years of ageOldest old: over 85 years of age

Elderly people………..Problem Entity?

(Verdecchia et al. EJC 2006)(Verdecchia et al. EJC 2006)

0

500

1000

1500

2000

2500

3000

3500

4000

Uomini Donne

25-29aa

30-34aa

35-39aa

40-44aa

45-49aa

50-54aa

55-59aa

60-64aa

65-69aa

70-74aa

75-79aa

80-84aa

Frequenza per Frequenza per 100.000100.000

Incidenza delle neoplasie Incidenza delle neoplasie ITALIA 2006 ITALIA 2006 proiezione per sesso ed etàproiezione per sesso ed età

50 - 69 vs 70 - 84Lung Cancer:Incidence&Mortalityt

(1/100.000 )

Source: Micheli A,et al. Current cancer profiles of the Italian Regions. Tumori 93(4), 2007

Prof. I. Carreca – Università degli Studi di Palermo

Q.

Concurrent CausesConcurrent Causes

Smoke Alcohol Low mobility

a

R

Industrial Pollution

1930

Incidence of Most Cancers

Year199019701950

a

R

Avoid Carcinogens at Work

Some Carcinogens in the Workplace

TroublesTroublesIn In

TreatingTreating

ELDERLY ELDERLY PATIENTSPATIENTS

Impact of Aging on Cancer

Comorbidity

Anemia

Body&Metabolism Disfunctions

PolyPharmacy

Frailty

Therapy

0%

10%

20%

30%

40%

50%

60%

Per

cen

t

55-59 60-64 65-69 70-74 75-79 80-84 85+Age Group

Hypertension

Previous malignancy

Arthritis

High severity heart disease

Stroke/TIA

COPD

Diabetes

Heart disease, moderate

Comorbidity Prevalence in Cancer Patients by Comorbidity Prevalence in Cancer Patients by AgeAge

Yancik R, Wesley M, Ries L, Havlik R, Edwards B, Yates, J, Effect of Age and Comorbidity in

Cancer Patients, JAMA, 2001, Vol 285, No.7, 885-892

COMORBIDITY INDEX AND SCORE OF CHARLSON & al

CONDITION ASSIGNED WEIGHT

•liver disease mild 1•diabetes 1•hemiplegia 2•renal disease moderate or severe 2•diabetes with end organ damage 2•any malignancy 2•leukemia 2•malignant lymphoma 2•liver disease. moderate or severe 3•metastatic solid malignancy 6•AIDS 6

COMORBIDITY INDEX AND SCORE OF CHARLSON & al...(continued)

CONDITION ASSIGNED WEIGHT

•myocardial infarction 1•congestive heart failure 1•peripheral vascular disease 1•cerebrovascular disease 1•dementia 1•chronic pulmonary disease 1•connective tissue disease 1•ulcer disease 1

Charlons’index related OS

1 2 3 4 5 6 7 8 9 10

100 %

Years Follow-up

Score 0

Score 1

Score 2

Score 3

Cancer Cancer

37.539.5

43.9

40.0 41.1

25.9

39.5

16.3

8.4

14.1 14.0

4.98.3

12.4

0

5

10

15

20

25

30

35

40

45

50

Lung Cancer Metastatic

Breast Cancer

Advanced

Ovarian Cancer

LymphomasAdvancedColorectal

Advanced Headand Neck

Total

Anemia Grade 1 or 2

Anemia Grade 3 or 4

Pati

ents

(%

)

Groopman JE, Itri LM. J Natl Cancer Inst. 1999;91:1616–1634.

Incidence of Anemia in Cancer PatientsIncidence of Anemia in Cancer Patients

Marrow reserves

Cellularity

• 30% fat - young• 50% fat - normal

• 70% fat - elderly

Aging affects chemotherapy toxicity and effectiveness

• Pharmacokinetic changes that increase toxicity– decreased volume of distribution (Vd)– decreased glomerular filtration rate (GFR)– decreased hepatic metabolism

– decreased intestinal absorption

• Pharmacodynamic changes that limit effectiveness– increased expression of multidrug resistance (MDR) gene– decreased apoptosis– increased tumour anoxia– decreased cell proliferation

Balducci L, Carreca I, et al Oncologist. 2000;5:224-237.

test changeBody weight/fat + 35%

Plasmatic volume - 8%Albumine - 10%globulins - 10%

Total body water - 17%Extracellular fluids - 40%

Cardiac electric stym/velocity - 20%Cardiac capacity - 40%Ejection fraction - 35%

Vital capacity - 60%glomerular filtration - 50%

Renal/GI ematic circulation - 40%

Physiological Aging-related ChangesPhysiological Aging-related Changes(20 to 80 yrs)(20 to 80 yrs)

Lung Cancer in Elderly(types frequence) Lung Cancer in Elderly(types frequence)

171,600 new cases reported; 158,900 deaths anticipated.

> 80% will be Non-small Cell types

> 70% have Stage III/IV disease at diagnosis

Cancer Statistics 1999, CA 49:8-31, 1999.

Troubles in treatment

Early micrometastasis

Inherited and acquired resistance to radiation and chemotherapy

Late diagnosis

Co-morbidity

Intestinal absorption in elderly

↓ gastric pH

↓ gastric emptying

↓ splanchnicblood flow

↓ digestiveenzymes

impaired mucosa

Creatinine Clearance and Aging

Hosoya T, et al Intern Med. 1995; 34(6): 520-7.

Renal Excretion

• Drugs completely excreted through the kidneys:– Methotrexate (*use with extreme care)– Carboplatin

• Drugs partially excreted through the kidneys:

– Epipodophyllotoxins

– Fludarabine

– Capecitabine

– Pemetrexed

• Drugs producing active or toxic metabolites excreted through the kidneys: – Cytarabine (high doses)

Hepatic Metabolism and Age: P450

• Liver flow reduced• Liver size decreases• Age related changes in

P450 microsomal systems

• Polypharmacy*– P450 inhibitors: grapefruit

juice– P450 inducers:

phenobarbital

*Ref: David Flockhart, MD, http://medicine.iupui.edu/flockhart/

CYP3A

Chemotherapy P450 Metabolism

Agent 1A2 2C9 2C19 2B6 2D6 3A4

Cyclophosphamide x x x

Docetaxel x

Doxorubicin x

Etoposide(+2E1) x (x)

Mitoxantrone

Paclitaxel (+2C8)

x

x x

Vinblastine

Vincristine

x

x

Dependence

ADL IADLBathing

Dressing

Toileting

Transfer

Continence

Feeding

Using telephone

Shopping

Cooking

House keeping

Laundry

Trasportation

Medication

Handling finances

Comprehensive Geriatric Assessment (CGA)

Comorbidity(Charlson scale)

Cardiovascular diseases

Respiratory diseases

Hepatic impairment

Renal impairment

Other major organ failures

Hematological malignancies

Metastatic solid tumors

AIDS

Polipharmacy(causes)

Long-term medications

Unecessary prescriptions

Increased risk of interactions

Cognition(Mini Mental Status Examination)

Memory

Orientation

Comprehension

Logical thinking

Poor Nutrition(causes)

Anorexia/cachexia

Depression

Bad dentition

Cognitive impairment

Functional impairment

Lack of caregivers

Toxicity of chemotherapy

Geriatric Syndromes

Dementia

Delirium

Severe depression

Frequent falls

Spontaneous fractures

Comprehensive Comprehensive geriatric geriatric assessment reveals assessment reveals stages of agingstages of aging

Balducci L, et al. Oncologist. 2000;5:224-237L. Balducci & W. B. Ershler Nature Reviews Cancer 5, 655-662

• Group 1Group 1– functionally independent, no

serious comorbidity– standard cancer treatment

• Group 2Group 2– partially dependent, 2

comorbid conditions– modified cancer treatment

• Group 3Group 3– dependent,3 comorbid

conditions, any geriatric syndrome

– palliative treatment

Frailty CriteriaFrailty Criteria

Age > 85 years

Dependence in oneor more ADL

Presence of threeor more comorbidities

Presence of one or moregeriatric syndromes

CaravaggioSt Jerome (1605-06)Oil on canvas, 118 x 81 cmMonastery, Montserrat

Management of elderly Management of elderly cancer patientscancer patients

Balducci L, et al. Oncologist. 2000;5:224-237.

Assessment

Group 1

Life expectancy

>Cancer

Life-prolongingtreatment

Palliation

Group 2 Group 3

<Cancer

Treatmenttolerance

Yes No

AlphaMed Press 1083-7159.

IS THERE OPTIMAL TXIS THERE OPTIMAL TXFOR THE ELDERLY WITH FOR THE ELDERLY WITH ADVANCED NSCLC?ADVANCED NSCLC?

Should Older Patients Receive Should Older Patients Receive Combination Chemotherapy For Combination Chemotherapy For Advanced Stage Non-Small Cell Lung Advanced Stage Non-Small Cell Lung Cancer (NSCLC)? An Analysis of Cancer (NSCLC)? An Analysis of Southwest Oncology Trials 9509 and Southwest Oncology Trials 9509 and 93089308

Karen Kelly, Sheryl Giarritta, Stephen Karen Kelly, Sheryl Giarritta, Stephen Hayes, Wallace Akerley, Paul Hesketh, Hayes, Wallace Akerley, Paul Hesketh, Antoinette Wozniak, Kathy Albain, John Antoinette Wozniak, Kathy Albain, John Crowley, Crowley, David R. GandaraDavid R. Gandara

OBJECTIVESOBJECTIVES

To determine the effect of age To determine the effect of age >> 70 70 on on

survival, toxicity, and drug delivery in survival, toxicity, and drug delivery in

patients with a good performance patients with a good performance status status

(PS) 0 - 1 receiving combination (PS) 0 - 1 receiving combination

chemotherapy for advanced stage chemotherapy for advanced stage NSCLC.NSCLC.

METHODSMETHODSA retrospective analysis was conducted A retrospective analysis was conducted on two recent SWOG trials in advanced on two recent SWOG trials in advanced NSCLC:NSCLC:

SWOG 9509Paclitaxel + Carboplatin versusVinorelbine + Cisplatin

SWOG 9308Vinorelbine + Cisplatin versus Cisplatin

METHODSMETHODS1.1. The analysis identified two age The analysis identified two age groups:groups:

patients < 70 years of age and patients < 70 years of age and patients patients >> 70 years of age. 70 years of age.

2.2. The cohorts were compared for:The cohorts were compared for:a) baseline characteristicsa) baseline characteristicsb) efficacy of treatmentb) efficacy of treatmentc) toxicityc) toxicityd) drug deliveryd) drug delivery

< 70(n=490)

> 70 (n=115) P-value

Hem Gr 0-2 119 (24%) 20 (17%)

Hem Gr 3-5 371 (76%) 95 (83%) .11*

Non-Hem Gr 0-2 225 (46%) 50 (44%)

Non-Hem Gr 3-5 265 (54%) 65 (56%) .63*

Max Tox Gr 0-2 60 (12%) 7 (6%)

Max Tox Gr 3-5 430 (88%) 108 (94%) .06*

Toxicity

* p-value for all grades of toxicities

CONCLUSIONSCONCLUSIONS

1.1. Relatively few older patients (19%) Relatively few older patients (19%)

entered these cooperative group entered these cooperative group trials.trials.

2.2. There was a trend toward shorterThere was a trend toward shorter

survival in older patients (p=.06).survival in older patients (p=.06).

3.3. Grade 3-5 toxicities occurred moreGrade 3-5 toxicities occurred more

frequently in older patients frequently in older patients (p=.06).(p=.06).

CONCLUSIONSCONCLUSIONS

4.4. Fewer patients of any age were able toFewer patients of any age were able tocomplete VC compared to PCb.complete VC compared to PCb.

5.5. A significantly larger number of olderA significantly larger number of older patients discontinued VC due to patients discontinued VC due to toxicity toxicity as compared to PCb.as compared to PCb.

6.6. Trials should be specifically designed Trials should be specifically designed forfor this population.this population.

TAX326: Study DesignTAX326: Study Design

RANDOMIZE

Docetaxel 75 mg/m2 IV + Cisplatin 75 mg/m2 IV q 3 wk

Docetaxel 75 mg/m2 IV + Carboplatin AUC 6 IV q 3 wk

Vinorelbine 25 mg/m2 IV 1, 8, 15, 22 + Cisplatin 100 mg/m2 IV d 1 q 4 wk

Premed: Dexamethasone 8 mg PO bid 6 doses (first dose 12 hours prior to Docetaxel infusion) for the Docetaxel groups.

: Stratification by

• Stage (IIIB or IV)

• Geographic region

Fossella FV. Eur J Cancer 2001;37(suppl 6):S154.

Survival Time (Mos.)

Cu

mu

lati

ve P

rob

ab

ilit

y

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0 3 6 9 12 15 18 21 24 27 30 33

Docetaxel Cisplatin

Vinorelbin Cisplatin

P = 0.044(adjusted log-rank)

SURVIVAL All patients D+CIS VS. V+CIS: Non-inferiority vs improved survival

TAX326

FUTURE PLANSFUTURE PLANS

SWOG 0027SWOG 0027 A phase II trial of vinorelbine followed by A phase II trial of vinorelbine followed by

docetaxel in advanced NSCLC patients docetaxel in advanced NSCLC patients with a with a PS of 2 or Age PS of 2 or Age >> 70 years old 70 years old

Vinorelbine25 mg/m2, d 1 & 8 every 3 weeks x 3

Docetaxel35 mg/m2 weekly 3/4 weeks x 3

NON-PLATINUM TXNON-PLATINUM TXIN ELDERLY WITH NSCLCIN ELDERLY WITH NSCLC

Randomized Trials in Elderly Randomized Trials in Elderly NSCLCNSCLC

Trial GroupComment

V vs BSC ELVISCompleted

GV vs V SICOGCompleted

G vs V vs GV ITA-MILESCompleted

Navelbine in the Elderly: Navelbine in the Elderly: SummarySummary

• E.L.V.I.S.: first Phase III trial demonstrating a E.L.V.I.S.: first Phase III trial demonstrating a survival advantage for single-agent survival advantage for single-agent chemotherapy vs BSCchemotherapy vs BSC

• Navelbine is generally well tolerated in the Navelbine is generally well tolerated in the elderly patientelderly patient– Age does not appear to change or increase Age does not appear to change or increase

toxicitytoxicity– Greater sensitivity of some older Greater sensitivity of some older

individuals cannot be ruled outindividuals cannot be ruled out

Gemcitabine Plus Vinorelbine vs Gemcitabine Plus Vinorelbine vs Vinorelbine Alone in Patients with NSCLC: Vinorelbine Alone in Patients with NSCLC: SICOG StudySICOG Study• Patients with Stage IIIB/IV NSCLCPatients with Stage IIIB/IV NSCLC

• Age Age 70 years at diagnosis 70 years at diagnosis

• Randomized to:Randomized to:– Vinorelbine 30 mg/mVinorelbine 30 mg/m22 d1, 8 q 3 weeks d1, 8 q 3 weeks vs.vs.– Vinorelbine 30 mg/mVinorelbine 30 mg/m22 d 1, 8 d 1, 8

– Gemcitabine 1250 mg/mGemcitabine 1250 mg/m22 d 1, d 8 d 1, d 8 administered q 3 weeksadministered q 3 weeks

Chemotherapy in Elderly Patients with Advanced

NSCLC

13%4.576 15%

Vinorelbine

30%*776 22%

Gemcitabine + Vinorelbine

Frasci‡

14%4.976 ---

BSC

32%*6.5 78 20%

VinorelbineGridelli*

1 YRMS (mo) N ResponseRegimenAuthor

*Gridelli, J Natl Cancer Inst 1999; 85:365-376.

‡Frasci et al, Proc ASCO 2001, 19:A1895* p<0.05

The MILES Phase III Trial: Gemcitabine + Vinorelbine vs Vinorelbine and vs

Gemcitabine in Elderly Advanced NSCLC Patients

NSCLC

70+ years old

Chemotherapy naïve

Stage IIIB

(N3 or pleural effusion) or

IV

PS 0-2

RANDOMI

ZE

Gridellii et al.ASCO 2001 Abstract 1230

Vinorelbine 30 mg/m2 d1,8Q 3 weeks

Gemcitabine 1000 mg/m2

d1,8Vinorelbine 25 mg/m2

d1,8 Q 3 weeks

Gemcitabine 1200 mg/m2

d1,8Q 3 weeks

MILES Trial - ConclusionsMILES Trial - Conclusions

• Polychemotherapy with gemcitabine Polychemotherapy with gemcitabine + vinorelbine does not improve + vinorelbine does not improve outcomes compared to single-agent outcomes compared to single-agent vinorelbine or gemcitabinevinorelbine or gemcitabine

• Single-agent chemotherapy should Single-agent chemotherapy should remain a standard for advanced remain a standard for advanced NSCLC elderly patientsNSCLC elderly patients

• Baseline QoL predictive of outcome, Baseline QoL predictive of outcome, though no difference observed in Qol though no difference observed in Qol or IADL between each arm or IADL between each arm

ASCO 2001 Abstract 1230 ORAL PRESENTATION

PS 2 NSCLCPS 2 NSCLC

What are the data?What are the data?

Impact of PS on OutcomeImpact of PS on Outcome

ECOG 1581Performance Objective MedianToxic

Status Response (%) Survival (wks) Deaths (%)

0 26 36 3

1 25 26 2

2 - 10 10

E1594 Schema

RANDOMIZE

Stratification Performance status0-1 vs. 2

Weight loss inprevious 6 months

<5% vs. 5%

Disease stage IIIBor IV

Presence or absence of brain metastases

Arm A: Cisplatin + PaclitaxelPaclitaxel: 135 mg/m2 over 24 hours,

day 1Cisplatin: 75 mg/m2 day 2 3-week cycle

Arm B: Cisplatin + GemcitabineGemcitabine: 1,000 mg/m2 days 1,8,15Cisplatin: 100 mg/m2 day 1 4-week cycle

Arm C: Cisplatin + DocetaxelDocetaxel: 75 mg/m2 day 1Cisplatin: 75 mg/m2 day 1 3-week cycle

Arm D: Carboplatin + PaclitaxelPaclitaxel: 225 mg/m2 over 3 hours,

day 1Carboplatin: AUC 6.0 day 1 3-week cycle

0 5 10 15 20 25 30

Months

0.0

0.2

0.4

0.6

0.8

1.0

Survival by Treatment Group Stage IIIB

Cis/PaclitaxelCis/GemcitabineCis/DocetaxelCarbo/Paclitaxel

0 5 10 15 20 25 30

Months

0.0

0.2

0.4

0.6

0.8

1.0

Survival by Treatment Group Stage IV

Cis/PaclitaxelCis/GemcitabineCis/DocetaxelCarbo/Paclitaxel

ECOG 1594: PS 2 SubanalysisECOG 1594: PS 2 SubanalysisCONCLUSIONSCONCLUSIONS

• 68 of 1207 pts enrolled had PS 268 of 1207 pts enrolled had PS 2

• Accrual suspended b/o untoward inc. of Gr 4/5 AEsAccrual suspended b/o untoward inc. of Gr 4/5 AEs

• Overall toxicity rate, however, did not differ Overall toxicity rate, however, did not differ significantly from that observed in PS 0-1 ptssignificantly from that observed in PS 0-1 pts

• 5 deaths (7.35% Grade 5 AE), but only two were 5 deaths (7.35% Grade 5 AE), but only two were directly attributable to Txdirectly attributable to Tx

• Med survival of 4.1 mo and 1-yr survival rate 19.1% Med survival of 4.1 mo and 1-yr survival rate 19.1% likely 2likely 2oo to disease process rather than toxicity to disease process rather than toxicity

……..

Sweeney et al Cancer 2001, 92:2639-47Sweeney et al Cancer 2001, 92:2639-47

ECOG 1594: PS 2 SubanalysisECOG 1594: PS 2 Subanalysis% G% G3 Heme Tox (n=64)3 Heme Tox (n=64)

PC GC DC PCb

N 18 13 18 15

ANC 60 58 59 47

PLT 0 50 0 7

H/H 25 33 6 20

NF 5 0 12* 0*1 gr 5

….Sweeney et al cancer 2001, 92:2639-47

ECOG 1594: PS 2 SubanalysisECOG 1594: PS 2 Subanalysis% Gr% Gr3 Non-Heme Tox (n=64)3 Non-Heme Tox (n=64)

PC GC DC PCb

Renal 6 24* 0 0

N/V 40 42 41 0

Diarrhea 5 8 18 0

Neuropathy 15 13 18 20

Allergy 6 0 12 0

Grade 5 0 8 6 0*One Gr 5 toxicity

….Sweeney et al Cancer 2001, 92:2639-47

PS 2 NSCLC: Treatment EfficacyPS 2 NSCLC: Treatment Efficacy

TrialTrial RR (%) RR (%) TTP (mo) TTP (mo) MS (m) MS (m) 1y OS 1y OS%%

ECOGECOG 14 14 1.7 1.7 4.1 4.1 19.1 19.1 HeCOGHeCOG -- -- 2.4 2.4 3.8 3.8 -- -- HeCOGHeCOG 11 3.8 11 3.8 5.9 5.9 20.9 20.9 CALGBPC 24CALGBPC 24 -- -- 4.7 4.7 18 18

PP 10 10 -- -- 2.4 2.4 10 10

Alternative Approach for Alternative Approach for PS 2 Patients with Advanced NSCLCPS 2 Patients with Advanced NSCLC

• Use “new” active single agentsUse “new” active single agents

• Use schedules with demonstrated favorable Use schedules with demonstrated favorable toxicity profilestoxicity profiles

• Use agents sequentiallyUse agents sequentially

• Avoid cisplatin (off study) although Avoid cisplatin (off study) although carboplatin combinations appear reasonablecarboplatin combinations appear reasonable

• Consider formal phase III study evaluating Consider formal phase III study evaluating new agent +/- carbo or new agent +/- targeted new agent +/- carbo or new agent +/- targeted TxTx

• Integrate quality of life into any future effortsIntegrate quality of life into any future efforts

Elderly vs “Poor Risk”Elderly vs “Poor Risk”Patients with Advanced NSCLCPatients with Advanced NSCLC

• ““Healthy” elderly fare as well as younger Healthy” elderly fare as well as younger patients with standard chemotherapy patients with standard chemotherapy approachesapproaches

• ““Poor risk” patients (PS2 ± low albumin ± Poor risk” patients (PS2 ± low albumin ± weight loss) fare poorlyweight loss) fare poorly

• Tolerability and potential benefits of Tolerability and potential benefits of chemotherapy in “poor risk” patients chemotherapy in “poor risk” patients remain to be determinedremain to be determined

Study Concepts: Elderly NSCLCStudy Concepts: Elderly NSCLC

• MONOTHERAPY VS PLATINUM MONOTHERAPY VS PLATINUM COMBINATIONS: e.g., COMBINATIONS: e.g., – gemcitabine +/- cisplatin or carboplatingemcitabine +/- cisplatin or carboplatin

– vinorelbine or gemcitabine +/- oxaliplatinvinorelbine or gemcitabine +/- oxaliplatin

• COMBINATION CHEMO & TARGETED TX: COMBINATION CHEMO & TARGETED TX: e.g., vinorelbine +/- OSI-774 or other EGFr e.g., vinorelbine +/- OSI-774 or other EGFr inhibitorinhibitor

• MONOTHERAPY COMPARISONS: e.g., MONOTHERAPY COMPARISONS: e.g., weekly vinorelbine vs weekly paclitaxel or weekly vinorelbine vs weekly paclitaxel or docetaxeldocetaxel

Randomized Trials with CT+/- Targeted Therapies

TRIAL TARGET CT GROUP COMMENT

ZD1839 EGFR TCb AstraZeneca Closed, no benefit

OSI 774 EGFR TCb Genentech/OSI Closed

ABXEGFR EGFR TCb Immunex Proposed

Herceptin Her-2/neu TCb ECOG Proposed

AG3340 MMP TCb Agouron Closed no benefit

AG3340 MMP GC Agouron Closed no benefit

BMS275291 MMP TCb BMSO Closed

TNP-470 Angiogenesis TCb MDACC Proposed (or ditched)

rhuMabVEGF Angiogenesis TCb ECOG Open

ISIS3521 PKC TCb ISIS Closed, no benefit

Deltaparin Metastases Std NCCTG Open

Alternative Approach for Alternative Approach for PS 2 Patients with Advanced NSCLCPS 2 Patients with Advanced NSCLC

• Use “new” active single agentsUse “new” active single agents

• Use schedules with demonstrated favorable Use schedules with demonstrated favorable toxicity profilestoxicity profiles

• Use agents sequentiallyUse agents sequentially

• Avoid cisplatin (off study) although Avoid cisplatin (off study) although carboplatin combinations appear reasonablecarboplatin combinations appear reasonable

• Consider formal phase III study evaluating Consider formal phase III study evaluating new agent +/- carbo or new agent +/- targeted new agent +/- carbo or new agent +/- targeted TxTx

• Integrate quality of life into any future effortsIntegrate quality of life into any future efforts

•Combination of new agents results in Combination of new agents results in similar efficacysimilar efficacy

•Overall improvement in median Overall improvement in median survival of 6 weekssurvival of 6 weeks

•Better palliation + better quality of Better palliation + better quality of Life ?Life ?

•Second line chemotherapy is usually Second line chemotherapy is usually ineffectiveineffective

NSCLC CHEMOTHERAPY IN ELDERLY CONCLUSIONS

therapymoni-toring

therapydiagnosis

today…

medicines

…towards the future

nutrition

predis-position

screening

lifestyle

targetedmonitoringprevention

therapymoni-toring

therapydiagnosis

Integrated Health CareIntegrated Health Carean evolving paradigman evolving paradigm

Individual Choice

Il crescente numero di persone anziane con diagnosi di cancro costituirà una delle maggiori sfide di salute pubblica negli anni a venire e

verosimilmente aumenterà le disparità nell’accesso alle cure sanitarie in tutte le parti d’Italia.

Le persone anziane con cancro frequentemente presentano comorbidità come diabete, malattie cardiovascolari e respiratorie,

complicanti il trattamento del loro tumore e aumentanti ulteriormente i costi.

A causa del numero crescente di tumori e degli alti ed esponenziali costi di diagnosi e trattamento, c’è un reale pericolo che la spesa nazionale per la salute non riesca a

far fronte alla domanda di cure per il cancro: il sistema potrebbe collassare o non permettere più a lungo termine

di fornire cure per tutti. Si presume che i servizi agli anziani saranno i primi a essere tagliati perché

costituiscono una larga proporzione dei costi totali per la salute.L’unica soluzione è investire oggi in prevenzione primaria,

così da ridurre l’incidenza del cancro nel futuro ed abbassare i costi di trattamenti e cure cliniche, riabilitative, sociali e psicologiche.

FIOGFIOGItalian Federation of Italian Federation of Oncology GeriatricsOncology Geriatrics

• AIM: To Improve researches and AIM: To Improve researches and studies in Elderly People with studies in Elderly People with CancerCancer

• R.BernabeiR.Bernabei• I.CarrecaI.Carreca• D.CovaD.Cova• P.FoaP.Foa• S.MonfardiniS.Monfardini• V.ZagonelV.Zagonel