Post on 07-Apr-2018
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Carcinoma PulmonarCarcinoma Pulmonar
Viviendo conCancer pulmonar
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PRINCIPALES CAUSAS DEPRINCIPALES CAUSAS DEMORTALIDADMORTALIDAD
PRINCIPALES CAUSAS DEPRINCIPALES CAUSAS DEMORTALIDADMORTALIDAD
% DEL TOTAL DE MUERTES
US data/Adapted from Cancer Journal for Clinicians , 1994.
33.5%
E n f .
C a r d
i o v a s
c u l a r
A c c i d
e n t e s E n
f .
C e r e b r o
v a s c
u l a r
C n
c e r
23.5%
6.7%4.3% 4.0% 3.7%
2.2%1.4% 1.2% 1.2%1.2%
D i a b
e t e s
E N f , .
O b s t r
u c t i v
a
c r n i c
a p u l m
o n a r
N e u m
o n a
e
I n f l u e
n z a
S u i c i
d i o
C i r r o
s i s h e
p t i c
a H I V
H o m i
c i d i o
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CARGA MUNDIAL DE CASOS
DE CANCER
9.1 MILLONES DE NUEVOS CASOS 6.2 MILLONES DE MUERTES
22.4 millones viviendo con Cncer
Almzr J. National Cancer Institute. 2004.
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ACTORES HEREDITARIOS FACTORES PERSONALE
FACTORES AMBIENTALES ESTILO DE VIDA
RAZONES DEL INCREMENTO EN INCIDENCIA
CONSUMO
DE ALCOHOL
TABACO
DIETA
VIRUSPARASITOS
EXPOSICIONAL SOL ORADIACION
ANCESTROS
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Los Estudios Basados en la Poblacin
CANAD:Leucemia
Regiones de Incidencia Ms Alta
BRASIL:Cncer cervical
EE.UU.:Cncer decolon
AUSTRALIA:Cncer de la
piel
CHINA:Cncer dehgado
Reino Unido:Cncer depulmn
JAPN:Cncer deestmago
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INCIDENCIA CANCER MUJEREStasa por 100,000
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INCIDENCIA DE CANCERHOMBRE
Tasa por 100,000
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Age-adjusted lung cancer death rates, USA(1930-1998) and the influence of smoking
80
60
40
20
0
1930 1940 1950 1960 1970 1980 1990
Rate per 100,000male/femalepopulation
Lung and bronchus (male)Lung and bronchus (female)
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Major presenting symptoms of
lung cancer
Baseline major presenting symptoms
0
20
40
60
80
100
HaemoptysisLoss of appetite
PainCoughDyspnoea
Patients(%)
Hollen et al 1999
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Squamous-cell carcinoma (~30%) Most commonly found in men Closely correlated with smoking
(dose dependent) Tends to spread locally More readily detected in sputum Highly expressed genes encoding
proteins with detoxification/anti-oxidant properties
Types of lung cancer: non-small-celllung cancer (NSCLC)
Adenocarcinoma (30-50%) Most common type of lung cancer
in women and non-smokers Lesions are usually peripheral Worldwide incidence increasing
Highly expressed genes encodingsmall-airway-associated andimmunologically related proteins
K-ras mutations frequently reported Bronchoalveolar carcinoma is a
subtype
Large-cell carcinoma (10-25%) Very primitive, undifferentiated cells
Lesions are usually peripheral
High tendency to metastasise
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Types of lung cancer: small-cellTypes of lung cancer: small-celllung cancer (SCLC)lung cancer (SCLC)
Approximately 20% of all lung cancersApproximately 20% of all lung cancers
Cellular classificationCellular classification
small-cell carcinomasmall-cell carcinoma
mixed small-cell/large-cell carcinomamixed small-cell/large-cell carcinoma
combined small-cell carcinomacombined small-cell carcinoma
Occurs almost exclusively in smokers and isOccurs almost exclusively in smokers and ismore prevalent in women than menmore prevalent in women than men
Lesions most commonly originate in central part of chestLesions most commonly originate in central part of chest
Tendency to disseminate early Tendency to disseminate early
Initially chemosensitive, becoming resistantInitially chemosensitive, becoming resistant
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Lung cancer diagnosis/stagingLung cancer diagnosis/stagingPhysical examination Detect signs
Visualise and sample mediastinal lymph nodes
Detect position, size, number of tumours
Detect chest wall invasion, mediastinallymphodenopathy, distant metastases
Lymph node staging
Detect changes in hormone production,and haematological manifestations of lung cancer
Precise location of tumour, obtain biopsy
Chest X-ray
CT scan
PET scan
Laboratory analysis
Bronchoscopy
Mediastinoscopy
FNA Cytology
NCCN Guidelines 2000FNA, fine-needle aspirate; CT, computed tomography;PET, positron emission tomography
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Molecular diagnosisMolecular diagnosis
GoalGoalto identify distinguishing molecularto identify distinguishing molecularcharacteristics of tumours in order tocharacteristics of tumours in order todevelop new diagnostic and therapeuticdevelop new diagnostic and therapeuticapproaches and predict responseapproaches and predict response
ProgressProgressnew molecular biomarkers and technologiesnew molecular biomarkers and technologiesare being identified and evaluated but areare being identified and evaluated but arenot yet routinely used in the clinicnot yet routinely used in the clinic
Gandara et al 2001;Mao 2001; Nacht et al 2001; Niklinski et al 2001
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Molecular abnormalities in lung cancer
Commonly observedgenetic changes
Tobaccocarcinogen
Inappropriate response to externalsignalsLoss of cell cycle control
Loss of apoptosis pathwayLoss of contact inhibition
Ability to metastasiseAngiogenesis
ImmortalityAutocrine growth loops
Atypical alveolar hyperplasia Premalignantadenomas
Lung cancer
Carcinomain situDysplasia
Bronchialmetaplasia
Normalepithelium
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NSCLC stagesLymph nodes
Mainbronchus
Contralaterallymph node
Metastasisto distantorgans
Invasion of chest wall
Stage IV
Stage 0Stage IAStage IIBStage IIIB
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5-year survival by TNM status inNSCLC
5-year survival by TNM status inNSCLC
Stage
IAIBIIAIIB
IIIAIIIBIV
TNM classification
T1N0M0T2N0M0T1N1M0
T2N1M0 or T3N0M0
T1-3N2M0 orT3N1M0T4Nany M0 or Tany N3M0
Tany Nany M1
5-year survival(%)61383424
1351
Mountain 1997
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NSCLC: treatment options overview
PDQ Guidelines 2000
Stage I
Lobectomy or segment/wedgeresection Curative radiotherapy if surgery is
contraindicated Adjuvant chemotherapy Adjuvant radiotherapy
Stage II
Lobectomy, pneumonectomy,segment/wedge resection asappropriate
Curative radiotherapy if surgerycontraindicated
Adjuvant chemotherapy
Adjuvant radiotherapyStage IIIA
Surgery alone Chemotherapy +
radiotherapy/neoadjuvant therapy
Post-operative radiotherapy Radiotherapy aloneStage IIIB
Chemotherapy alone Chemotherapy + radiotherapy Radiotherapy alone
Stage IV Chemotherapy (platinum based),modest survival benefits
New chemotherapy agents
External beam radiotherapy(palliative relief) Endobronchial laser or brachytherapy for obstruction
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Advanced NSCLC:new chemotherapy agents
Platinum-based combination therapy givesbetter response rates than monotherapy andremains the gold standard for first-line therapyfor advanced diseasePaclitaxel, vinorelbine, docetaxel, gemcitabine
In the past 3 decades, median survival inNSCLC patients has only improved byapproximately 2 months
Corey Langer 2000; Breathnach et al 2001; Schiller et al 2002
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First-line combination chemotherapy:recent randomised trials in advanced
NSCLC (1)Study
Le Chevalier et al 1994
Bonomiet al 1996
Crinoet al 1998Belaniet al 1998
Cardenalet al 1999
Regimens
Vindesine/cisplatinVinorelbine/cisplatin
Etoposide/cisplatinPaclitaxel (135)/cisplatinPaclitaxel (250)/cisplatin/GCSF
Mitomycin/ifosfamide/cisplatinGemcitabine/cisplatinEtoposide/cisplatinPaclitaxel/carboplatin
Etoposide/cisplatinGemcitabine/cisplatin
Mediansurvival(months)
7.49.2*
7.79.610.0
8.88.1
8.3**8.3**
7.28.7
1-year survival
(%)
2836
31.636.939.1
--
35**35**
2632
Tumour response
(%)
19.030.0*
12.026.5*32.1*
2840*14.021.6
21.940.6*
*p
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Non-small cell lung cancer chemotherapy:19752005
Responserate
1-year survival
2-year survival
No chemotherapy 0% 10% 0%Active single agent 15% 20% 10%
Active two-drugcombination
25% 35% 20%
Active three-drug
combination
35% 35% 20%
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First-line combination chemotherapy:recent randomised trials in advanced
NSCLC (2)Study
Kellyet al 2001
Schiller et al 2002
Fossella2001
Regimens
Vinorelbine (25)/cisplatin (100)Paclitaxel (225)/carboplatin (AUC 6)
Paclitaxel (135)/cisplatin (75)Gemcitabine (1000)/cisplatin (100)Docetaxel (75)/cisplatin (75)Paclitaxel (225)/carboplatin (AUC 6)
Docetaxel (75)/cisplatin (75)Docetaxel (75)/carboplatin (AUC 6)Vinorelbine (25)/cisplatin (100)
Mediansurvival(months)
88
7.88.17.48.1
10.99.110
1-year survival
(%)
3638
31363134
473842
Tumour response
(%)
2825
21221717
---
Fossella 2001; Kelly et al 2001; Schiller et al 2002
-, not reported
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Second-line docetaxel for advanced NSCLC
Shepherd et al 2000
Median survival(months)1-year survival(%)
Log rank: p=0.01
Docetaxel 75 mg/m2 (n=55)Best supportive care (n=49)
0 3 6 9 12 15 18 21
Cumulativeprobability
0.0
0.2
0.4
0.6
0.8
1.0
Docetaxel75 mg/m2
7.5
37
Bestsupportive
care4.6
12
Months
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NSCLC stage IIIA: role of NSCLC stage IIIA: role of neoadjuvant chemotherapyneoadjuvant chemotherapy
Surgical resection alone fails to cure the majority of patientsSurgical resection alone fails to cure the majority of patientswith NSCLCwith NSCLCNeoadjuvant chemotherapy still experimentalNeoadjuvant chemotherapy still experimental3 randomised trials showed improvement in survival with3 randomised trials showed improvement in survival withneoadjuvant cisplatin-based chemotherapy (Bunn et alneoadjuvant cisplatin-based chemotherapy (Bunn et al2000)2000)An additional Phase III trial of gemcitabine/cisplatin hasAn additional Phase III trial of gemcitabine/cisplatin hasdemonstrated response in >70% of patients, with tumourdemonstrated response in >70% of patients, with tumourdownstaging of nodes in 53% (van Zandwijk 2000)downstaging of nodes in 53% (van Zandwijk 2000)
Neoadjuvant docetaxel was associated with a trend towardsNeoadjuvant docetaxel was associated with a trend towardslonger median survival in a large Phase III trial (Mattsonlonger median survival in a large Phase III trial (Mattson2001)2001)
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NSCLC stage IIIA/IIIB:chemotherapy and radiotherapy
Study
Furuse et al
1999, Phase IIICurran et al2000, Phase III
Gandara et al2000, Phase II
Responserate (%)
66.0
84.0-
-
-
--
Treatment regimens
I) CT with sequential Rx
II) CT with concurrent RxI) Cis/vinb followed by
sequential Rx on Day 50II) Cis/vinb with concurrent Rx
from Day 1
III) Cis/VP-16 with concurrent Rxtwice-daily from Day 1
I) Cis/etop/Rx cis/etopII) Cis/etop/Rx docetaxel
Mediansurvival(months)
13.3
16.514.6
17.0
15.6
1520
CT, chemotherapy (cisplatin/vindesine/mitomycin); Rx, radiotherapy;cis, cisplatin; vinb, vinblastine; etop, etoposide; -, not reported
No.patients
320
611
-71
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Lung cancer:
future developmentsCurrent treatment remains unsatisfactoryEarlier diagnosis
New molecular-based classification
Improved treatment
novel targeted biological agents, immunologicalapproaches, gene therapy
less toxic combinations
Prevention
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Earlier diagnosis
Obstructive lung disease (chronic bronchitis andemphysema)
Genetic risk factors
Sputum cytologyMolecular tumour markers
Low-dose spiral computed tomography
Positron emission tomographyLaser-induced fluorescence endoscope (LIFE)bronchoscopy
Edell 1997; Hirsch 2001
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Sequential changes during lung cancer pathogenesisEarly Intermediate Late
Normalepithelium Hyperplasia Dysplasia CIS
Invasivecarcinoma
~80%3p LOH/small telomeric deletions 3p LOH/contiguous deletions
~50%Microsatellite alterations
~70%9p21 LOH
~80%Telomerase dysregulation Telomerase upregulation
~60%myc overexpression
~80%8p21-23 LOH
~40%Neoangiogenesis
~40%Loss of Fhit immunostaining
~70%p53 LOH p53 mutations~80%
Aneuploidy
~100%Methylation
~30%5q21 APC-MCC LOH
~20%K-ras mutation
Hirsch et al 2001LOH, loss of heterozygosity
d d
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Prognostic and predictivePrognostic and predictivefactorsfactors
p53 statusp53 statusOther cell cycle components including p27, p15, p16,Other cell cycle components including p27, p15, p16,pRb, cyclin and CDK pRb, cyclin and CDK
K-ras mutationsK-ras mutations
HER2/neu and epidermal growth factor receptor (EGFR)HER2/neu and epidermal growth factor receptor (EGFR)Beta tubulinBeta tubulin
Expression of matrix metalloproteinase and inhibitorsExpression of matrix metalloproteinase and inhibitors
DNA topoisomerase IIDNA topoisomerase II and IIand II
Single nucleotide polymorphism in myeloperoxidase geneSingle nucleotide polymorphism in myeloperoxidase genereduces risk of lung cancerreduces risk of lung cancer
Heparin-binding growth factor pleiotrophinHeparin-binding growth factor pleiotrophin
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Strategies for signalling inhibition
Tyrosine kinaseinhibitors (TKIs)
Immune
effector cell
Anti-ligand
mAbsBispecificAbs
Anti-receptor mAbs
Ligand/toxinconjugate
scFv/toxinconjugates
Ligand-genisteinconjugates
Intracellular scFvs
Nucleus
Antisense
Inhibitors of other signallingmolecules
l b l l h
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Novel biological approachesNovel biological approaches(1)(1)
Inhibitors of the EGFR familyInhibitors of the EGFR familysmall molecule TKIs of EGFR, eg gefitinib, erlotinibsmall molecule TKIs of EGFR, eg gefitinib, erlotinibmonoclonal antibodies to EGFR, eg cetuximabmonoclonal antibodies to EGFR, eg cetuximabmonoclonal antibodies to HER2, eg trastuzumabmonoclonal antibodies to HER2, eg trastuzumab
Farnesyl transferase inhibitorsFarnesyl transferase inhibitorsInducers of apoptosis, eg cyclooxygenase-2 (COX-2)Inducers of apoptosis, eg cyclooxygenase-2 (COX-2)inhibitors, inhibitors of protein kinase C, gene therapy,inhibitors, inhibitors of protein kinase C, gene therapy,bcl-2 antisense oligonucleotidebcl-2 antisense oligonucleotide
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DNA
Mode of action of EGFR inhibitors
Membrane
Extracellular
Intracellular
R
K
R
K EGFR-TKIEGFR-TKI
SignallingProliferationCell survival
(anti-apoptosis)
Growth factors
Chemotherapy/radiotherapy sensitivity
Angiogenesis
Metastasis
R, epidermal growth factor receptor
EGF/TGF
Antibody
Cli i l d l f
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Clinical development of anti-EGFR agents in NSCLC
Gefitinib
Phase II studies of once-daily, oral gefitinib in NSCLC(Kris et al 2002; Fukuoka et al 2003)
antitumour activity, symptom relief, favourable safety profile
Phase III first-line combination studies in stage III/IV NSCLC(Giaccone et al 2002; Johnson et al 2002)
no added benefit over combination chemotherapy alone
ErlotinibPhase II study in EGFR-positive, previously treated stage IIIB/IV NSCLC (Perez-Soler et al 2001)
antitumour activity, favourable safety profile
Phase III first-line combination and third-line monotherapy studies ongoing inNSCLC
CetuximabPhase I study of cetuximab alone and in combination with cisplatin in patientswith EGFR-positive advanced tumours
Phase II cetuximab combination studies ongoing in EGFR-positive NSCLC
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Tumour angiogenesisTumour
4. Appearanceof newtumour
vasculature
1. Secretion of angiogenic
factors
3. Endothelialcell proliferation
and migration
2. Proteolyticdestruction of extracellular matrix
Sprouting capillary
l b l l hN l bi l i l h
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Novel biological approachesNovel biological approaches(2)(2)
Anti-angiogenic agentsAnti-angiogenic agentsmonoclonal antibodies, eg bevacizumabmonoclonal antibodies, eg bevacizumab(rhuMab-VEGF)(rhuMab-VEGF)VEGF receptor TKIs, eg ZD6474, PTK787VEGF receptor TKIs, eg ZD6474, PTK787
matrix metalloproteinase inhibitorsmatrix metalloproteinase inhibitorsthalidomidethalidomide
Vascular targeting agents,Vascular targeting agents,eg combretastatin A4 phosphate, ZD6126eg combretastatin A4 phosphate, ZD6126
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Sponsor
Genentech
ISIS Pharmaceuticals
NCI, ECOG
Abgenix, Immunex
Roche, Genentech,OSI Pharmaceuticals
Roche, Genentech,OSI Pharmaceuticals
Roche, Genentech,OSI Pharmaceuticals
Investigational regimen
Paclitaxel/carboplatin/erlotinib
Paclitaxel/carboplatin/ISIS 3521
Paclitaxel/carboplatin/radiotherapy/thalidomide
Paclitaxel/carboplatin/ABX-EGF
Gemcitabine/cisplatin/erlotinib
Paclitaxel/carboplatin/erlotinib
Erlotinib
Reference regimen
Paclitaxel/carboplatin
Paclitaxel/carboplatin
Paclitaxel/carboplatin/radiotherapy
Paclitaxel/carboplatin
Gemcitabine/cisplatin/placebo
Paclitaxel/carboplatin/placebo
Placebo
NCI, National Cancer Institute; SWOG, Southwest Oncology Group; ECOG, EasternCooperative Oncology Group
NSCLC stage IIIB and IV:Phase III trials in progress, July 2003 (2)
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Sponsor
NCI, ECOG
NCIC-ClinicalTrials Group
NCI, MemorialSloan-Kettering
Cancer Center
Investigational regimen
Paclitaxel/carboplatin/bevacizumab
Paclitaxel/carboplatin/BMS-275291
Oblimersen/docetaxel
Referenceregimen
Paclitaxel/carboplatin
Paclitaxel/carboplatin/placebo
Docetaxel
NCI, National Cancer Institute; ECOG, Eastern Cooperative Oncology Group;SWOG, Southwest Oncology Group;
NSCLC stage IIIB and IV:Phase II/III trials in progress, July 2003
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SCLC:Phase III trials in progress, July 2003
Sponsor
EORTC LungCancer
CooperativeGroup
VrijeUniversiteit
MedischCentrum
Investigationalregimen
Adjuvant BCG andmonoclonal antibody
BEC2
Cyclophosphamide/doxorubicin/
etoposide
Diseasestage
Limited
Extensive
Referenceregimen
First-line combinedmodality treatment
(at least 2-drugchemotherapy and chestradiotherapy)
Carboplatin/paclitaxel
EORTC, European Organization for Research and Treatment of Cancer; BCG, BacillusCalmette Guerin
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SummarySummary
Despite improved detection and advances inDespite improved detection and advances intreatment modalities, only limited progress hastreatment modalities, only limited progress hasbeen made in the outcome for patients with lungbeen made in the outcome for patients with lungcancercancer
Targeted molecular therapeutic agents offer new Targeted molecular therapeutic agents offer newhope for the futurehope for the future
Through molecular characterisation of a patients Through molecular characterisation of a patientstumour, it may become possible to offer moretumour, it may become possible to offer morerational, less toxic treatmentrational, less toxic treatment
nc enc a e ancer
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Copyright 2005 American Cancer Society
From Jemal, A. et al.
CA Cancer J Clin 2005;55:10-30.
nc enc a e ancer
Lung cancer is the mostLung cancer is the most
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Lung cancer is the mostLung cancer is the mostcommon cancer worldwide,common cancer worldwide,
yetyetlung cancer is surrounded by negativity:lung cancer is surrounded by negativity:
Stigmatised by its association with tobacco seen asStigmatised by its association with tobacco seen asself inflictedself inflicted
Low media profile - underreportedLow media profile - underreported Little celebrity interestLittle celebrity interest People do not hear about progress in lung cancer detectionPeople do not hear about progress in lung cancer detection
and treatmentand treatment Some clinician and general public hopelessness about lungSome clinician and general public hopelessness about lung
cancer and treatment outcomescancer and treatment outcomes Insufficient funding for lung cancer research/treatmentsInsufficient funding for lung cancer research/treatments Scarcity of support services for lung cancer patientsScarcity of support services for lung cancer patients Disparate access to care and treatmentDisparate access to care and treatment
NSCLC:NSCLC:
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NSCLC:NSCLC:how oncologists would choose to behow oncologists would choose to be
treated (1987)treated (1987)
Mackillop WJ, et al. Int J Radiat Oncol Biol Phys 1987;13:92934
118 Canadian doctorswho treat lung cancer
Yes; 3%
If they had NSCLC, would they choose tobe treated with chemotherapy?
For symptomaticmetastatic disease
For advanced diseaseconfined to the chest
After surgery for early disease
No
Yes; 9% Yes; 15%
No No
NSCLC: how oncologists: ow onco og sts
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NSCLC: how oncologists: ow onco og stswould choose to bewould choose to be
treated (1994)treated (1994)105 Japanese doctorswho treat lung cancer
Yes; 24%
If they had NSCLC, would they choose tobe treated with chemotherapy?
For symptomaticmetastatic disease
After surgery for locally advanced
disease
After surgery for early disease
(stage I)
No
Yes; 62% Yes; 33%
No No
Motohiro A, et al. Lung Cancer 1994;11(12):4350
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Patient power in lungPatient power in lungcancer is difficultcancer is difficult
Few lung cancer patients live long enough toFew lung cancer patients live long enough toadvocate on their own behalf advocate on their own behalf
Almost all lung cancer organizationsAlmost all lung cancer organizationsworldwide were started by non-patientsworldwide were started by non-patients
Few lung cancer specific organizations inFew lung cancer specific organizations in
existenceexistenceCancer charities focus their efforts on anti-Cancer charities focus their efforts on anti-tobacco campaigns, not on promoting thetobacco campaigns, not on promoting therights of lung cancer patientsrights of lung cancer patients
What can patient advocatesWhat can patient advocates
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What can patient advocatesWhat can patient advocatesdo to improve lung cancerdo to improve lung cancer
outcomes?outcomes?Raise the profile of the diseaseRaise the profile of the diseaseraise lung cancer awarenessraise lung cancer awareness
amplify the patient voiceamplify the patient voice
create more positive images of the disease and treatmentcreate more positive images of the disease and treatment
Help improve early detection ratesHelp improve early detection ratesraise awareness of signs and symptomsraise awareness of signs and symptoms
Help improve treatment and careHelp improve treatment and careprovide information and supportprovide information and support
educate public and professionalseducate public and professionals
Support lung cancer researchSupport lung cancer researchsecure fundingsecure funding
raise awareness and recruitment for clinical trialsraise awareness and recruitment for clinical trials
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The general response toThe general response tolung cancerlung cancer
Smokers and non-smokers oftenSmokers and non-smokers oftenfeel they are held responsible forfeel they are held responsible fortheir diseasetheir disease
family or friends not in touch since diagnosisfamily or friends not in touch since diagnosis
friends and acquaintances cross the road tofriends and acquaintances cross the road toavoid contactavoid contact
it is assumed patients lung cancer wasit is assumed patients lung cancer wascaused by smoking even when the patientcaused by smoking even when the patientdenied ever smokingdenied ever smoking
many anti-smoking campaigns underlinemany anti-smoking campaigns underlinesmoking and its association with lung cancersmoking and its association with lung cancer
h f
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The patient perspective of The patient perspective of lung cancerlung cancer
Disbelief Disbelief
UncertaintyUncertainty
What did he say now? (jargon)What did he say now? (jargon)
the long wait for diagnosisthe long wait for diagnosis
Is everything possible being done?Is everything possible being done?
contradictory statements by physicianscontradictory statements by physicians
second opinionssecond opinionsAn impression from 1200 questions posed via an interative forum
on the Longkanker Informatiecentrum website
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The patient perspective of The patient perspective of lung cancer (contd)lung cancer (contd)
FearFear
poor prognosispoor prognosis
few treatment optionsfew treatment options
Unrealistic hope of recoveryUnrealistic hope of recovery
GuiltGuilt
Dealing with the responseDealing with the responseof family and friendsof family and friends
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The patient perspective onThe patient perspective onexperimental drugsexperimental drugs
Last hopeLast hope
Well try anything!Well try anything!
Unrealistic expectationsUnrealistic expectations
New drugs are much better than older drugsNew drugs are much better than older drugs
Unrealistic media coverageUnrealistic media coverage
AccessibilityAccessibility
Are they not giving this to me because its expensive?Are they not giving this to me because its expensive?
Lack of understanding about role of therapyLack of understanding about role of therapy
h h
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communicating with thecommunicating with thepalliative patient: apalliative patient: a
physician perspectivephysician perspectiveCommunicating on patient levelCommunicating on patient levelDecision to start treatment or notDecision to start treatment or not
Decision to stop treatmentDecision to stop treatment
Bringing bad newsBringing bad news
Answering prognosis questionsAnswering prognosis questions
Needing more time than is availableNeeding more time than is available
communicating with thecommunicating with the
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communicating with thecommunicating with thepalliative patient: apalliative patient: a
physician perspectivephysician perspective(contd)(contd)Multidisciplinary inconsistencies in messagesMultidisciplinary inconsistencies in messages Too high treatment expectations from patients Too high treatment expectations from patients
Adapting to emotional responses in different patientsAdapting to emotional responses in different patients
Finding a balance between hope and realityFinding a balance between hope and reality
Family wants are different to patient needsFamily wants are different to patient needs
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Communicating for successCommunicating for success
ContentContentwhat information do you give?what information do you give?
how do you give it? ( e.g. how to make it easy)how do you give it? ( e.g. how to make it easy)
how can internet support you in conveying your message?how can internet support you in conveying your message?
RelationshipRelationshipwhat is the effect of the patient personality on you andwhat is the effect of the patient personality on you andvice- versa? (e.g. do you have a relationship of equalityvice- versa? (e.g. do you have a relationship of equalitywith your patient?)with your patient?)
OrganisationOrganisationhow is communication organised in your department?how is communication organised in your department?(e.g., what is the supportive role of oncology nurses?)(e.g., what is the supportive role of oncology nurses?)
h l h lH h l h l
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If you get frustrated that you cant offer your patients the mostIf you get frustrated that you cant offer your patients the mostoptimal treatment:optimal treatment: work with uswork with us
Ensure clinicians are informed:Ensure clinicians are informed: help us to address attitudes of help us to address attitudes of some clinicians to lung cancer and its treatmentsome clinicians to lung cancer and its treatment
Create informed patients and carers:Create informed patients and carers: partner with us to providepartner with us to providegood internet and written informationgood internet and written information
Empower all members of the patient network:Empower all members of the patient network: collaboratecollaborateefforts to reinforce the important roles of each stakeholder inefforts to reinforce the important roles of each stakeholder inthe patient treatment networkthe patient treatment network
How can we help the lungHow can we help the lungcancer patient together?cancer patient together?
If we work togetherwe can improve the livesof lung cancer
patients worldwide
Th lTh l
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The lung cancerThe lung cancerepidemic in Europe*epidemic in Europe*
Bray F, et al. Eur J Cancer 2002;38:99166
*Data for 1995
NSCLC i ifiNSCLC i ifi t t
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NSCLC: significant unmetNSCLC: significant unmetmedical needmedical need
Early (stage I;II;IIIa): 30%Early (stage I;II;IIIa): 30%
Locally advanced (stage IIIa;IIIb): 30%Locally advanced (stage IIIa;IIIb): 30%
Metastatic (stage IV): 40%Metastatic (stage IV): 40%
Limited efficacy of standard regimensLimited efficacy of standard regimens
Issues with tolerability and acceptability of Issues with tolerability and acceptability of chemotherapy agentschemotherapy agents
Advanced NSCLC: whatvance : w at
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Advanced NSCLC: whatvance : w atshould our treatmentshould our treatment
goals be for patients?goals be for patients?Longer lifeLonger lifeincreased overall survival (OS)increased overall survival (OS)
Better lifeBetter lifeimproved response rate (RR)improved response rate (RR)
prolonged time to progression (TTP)prolonged time to progression (TTP)
symptomatic improvementsymptomatic improvement
reduced toxicityreduced toxicity
improved quality of life (QoL)improved quality of life (QoL)
L lif L g lif
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Stage at diagnosis Early stage Locally advanced Distant
Standard therapy Surgery RT CTRT CT +CT + supportive care
2-year survival rate 2530%5-year survival rate 40% 3%
44% with surgery + CTRT = radiotherapyCT = chemotherapy Adapted from Jemal A, et al. CA Cancer J Clin 2003;53:526
Longer life . . . are weLonger life . . . are wemeeting the objective?meeting the objective?
Patients(%)
5040
30
2010
0
Better e are weetter e are we
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Better e . . . are weetter e . . . are wemeetingmeeting
the objective?the objective?
Significant toxicitySignificant toxicity myelosuppressionmyelosuppression neuropathyneuropathy
Limited improvement in QoLLimited improvement in QoL
i.v. administrationi.v. administration
Need for premedicationNeed for premedication
Benefits
Disadvantages Tumour controlImproved survival
C h e m o t h e r a p y
Th t t t lg ithThe treatment algorithm
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The treatment algorithmThe treatment algorithmfor NSCLCfor NSCLC
NSCLCEarly(stage I/II/IIIa) Advanced(stage IIIb/IV)
First-line
Second-/third-line
Suitable for chemotherapy? Yes No
(PS4, frailelderly)
PT-baseddoublet BSC
Singleagent
No YesElderly/PS23?
Relapse
Surgery +chemotherapy
Radiotherapy(if unfit for surgery)
PS = performance status; PT = platinum; BSC = best supportive care
Chemotherapy docetaxel pemetrexed
Tarceva
Locallyadvanced
Chemotherapy(PT doublet)
+ concomitantradiotherapy
Th t t t lg ithThe treatment algorithm
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The treatment algorithmThe treatment algorithmfor NSCLC (contd)for NSCLC (contd)
NSCLC Advanced(stage IIIb/IV)
First-line
Suitable for chemotherapy? Yes No
(PS4, frailelderly)
PT-baseddoublet BSC
Singleagent
No YesElderly/PS23?
Fi t li h thFirst line chemotherapy
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Median survival with chemotherapy is
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DRAMATICA RESPUESTA A ERLOTINIB