Treatment of Special Populations:Elderly and PS2 patients
Cattedra di Oncologia Medica e U.S. di OncoGeriatria,Policlinico Universitario di Palermo
Dir. :[email protected]
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