Carcinoma Pulmonar.1

8/6/2019 Carcinoma Pulmonar.1

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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)


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


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



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/radiotherapy


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/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

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Carcinoma Pulmonar.1