Download classification of cytotoxic agents

LUNG CANCER
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Worldwide incidence*
*Incidence per 100,000 population.
Western
Europe
Male
Female
54.8
8.1
Eastern
Europe
Male
Female
75.9
10.3
Japan
Male
Female
39.3
11.2
Australia
Male
New Zealand Female
47.6
16.1
China
Male
Female
34.7
13.4
Northern
Africa
Male
Female
12.9
2.6
Southern
Africa
Male
Female
29.1
7.7
North
America
Male
Female
69.6
32.9
Central
America
Male
Female
19.3
7.9
Temperate
South America Male
Female
Clinical Division of Oncology
Department of Medicine I
Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64.
55.1
7.6
Medical University of
Vienna, Austria
LUNG CANCER
5-year survival rates
Northwestern
Europe
Clinical Division of Oncology
Department of Medicine I
Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64.
7%
Eastern
Europe
12%
Japan
21%
Australia
New Zealand
13%
China
8%
Middle East/
Northern Africa
8%
Sub-Saharan
Africa
10%
North
America
20%
Latin America/
Caribbean
14%
Medical University of
Vienna, Austria
LUNG CANCER
Risk factors
Cigarette smoking
Smoking has been implicated in:
80% of lung cancer deaths in men
75% of lung cancer deaths in women
17% of lung cancer cases in nonsmokers
28% of all cancer deaths
35-year old male who smokes 25 cigarettes per day:
13% risk of dying from lung cancer before age 75
10% risk of dying from coronary disease
28% risk of dying from smoking-related disease
Clinical Division of Oncology
Department of Medicine I
American Cancer Society. Cancer Facts & Figures–2001.
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 6th ed. 2001;925-983.
Medical University of
Vienna, Austria
LUNG CANCER
Impact of smoking on risk
Cigarettes
smoked/day
Risk of developing
lung cancer*
Risk after 16 years
of smoking cessation*
1-20
10.3-fold
1.6-fold
20
21.2-fold
4.0-fold
*Data in women; risk compared to nonsmokers.
Clinical Division of Oncology
Department of Medicine I
Humphrey EW, et al. The American Cancer Society Textbook of
Clinical Oncology. 2nd ed. 1995;220-235.
Medical University of
Vienna, Austria
LUNG CANCER
Lung cancer control
Health policy
Smoke-free environments
Restricted advertising
Educational curriculum
Economic incentives
Cigarette tax
Health insurance discount for nonsmokers
Media coverage/advocacy
Social stigma associated with smoking
Clinical Division of Oncology
Department of Medicine I
Bal DG, et al. The American Cancer Society Textbook of Clinical
Oncology. 2nd ed. 1995;40-63.
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology.
6th ed. 2001;925-983.
Medical University of
Vienna, Austria
LUNG CANCER
Risk factors other than smoking
Asbestos
Radon (from mining or indoor exposure)
Other “occupational carcinogens”
Chloromethyl ether
Chromium
Nickel
Arsenic
Diet (vitamins A, C, E, -carotene deficiencies)
Genetic/familial factors
Clinical Division of Oncology
Department of Medicine I
Figlin RA, et al. Cancer Treatment. 1995;385-413.
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 6th ed. 2001;925-983.
Medical University of
Vienna, Austria
LUNG CANCER
Genetic abnormalities
Genetic abnormality
NSCLC
SCLC
Chromosome 3p
deletions
X
X
p53 gene mutation
X*
X
Rb gene abnormalities
X
X*
myc oncogene family
X*
X
K-ras oncogene
mutation
X
*In cancer cell lines.
Clinical Division of Oncology
Department of Medicine I
Figlin RA, et al. Cancer Treatment. 1995;385-413.
Lassen U, et al. Cancer Treatment. 1995;414-420.
Medical University of
Vienna, Austria
LUNG CANCER
Screening
Early NCI trial in high-risk population
sputum cytology every 4 months
chest radiograph annually
cancers identified in screened population were more often
early-stage (40% versus 15% in unscreened)
5-year survival of 35% versus 13% in general population
No difference in overall mortality
PLCO study of annual chest radiographs underway
http://www.cancernet.nci.nih.gov/
Clinical Division of Oncology
Medical University of
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 6th
Department of Medicine I
Vienna, Austria
ed. 2001;925-983.
LUNG CANCER
Diagnosis
Diagnosis of suspected lung cancer
Chest X-ray film
CT scan
PET scan (?)
Peripheral tumor
Central tumor
Unresolving segmental pneumonia
Hemoptysis
Options
Percutaneous fine-needle aspiration
Bronchoscopy
Video-assisted thoracoscopy
Thoracotomy
Clinical Division of Oncology
Department of Medicine I
Options
Sputum cytology
Bronchoscopy
Percutaneous fine-needle aspiration
Thoracotomy
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 6th ed. 2001;925-983.
Medical University of
Vienna, Austria
LUNG CANCER
Bronchoscopy
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Radiography
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
CT Scan
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
MRI
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Bone scintigraphy
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Lung cancer Pathology
• Non small cell carcinoma
Adenocarcinoma
Squamous cell carcinoma
Large cell carcinoma
• Neuroendocrine (NE) carcinomas
Carcinoid
Small cell carcinoma
Large cell neuroendocrine carcinoma
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Incidence of major
histologic types*
Small-cell
carcinoma
Adenocarcinoma
15%
Large-cell
carcinoma
* Numbers do not sum to 100% because
of differences in diagnostic criteria.
Clinical Division of Oncology
Department of Medicine I
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 5th ed. 1997;858-911.
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 6th ed. 2001;925-983.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Histologic types
68
Smokers vs nonsmokers
Squamous Cell
56
Adenocarcinoma
Large Cell
Small Cell
Bronchoalveolar
38
35
27
23
23
21
22
17
13
10
9
6
5
3
1
Smoker (%)
Male
Clinical Division of Oncology
Department of Medicine I
Nonsmoker (%)
Smoker (%)
Rosenow and Carr.
11
10
2
Nonsmoker (%)
Female
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Signs and symptoms at diagnosis
40
Cough
30
Dyspnea
Hemoptysis
Pneumonitis
40
25
Chest Pain
40
15
15
35
25
40
Weight Loss
Generalized Weakness
35
Anorexia
35
Fever
15
Anemia
15
Clinical Division of Oncology
Department of Medicine I
75
50
Frequency (%)
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Evaluation of disease
extent
Physical examination
Chest X-ray film
CT scan (chest, upper abdomen)
Bronchoscopy
SGOT, AST, CEA
PET scan (?)
Suspected mediastinal spread
 Transbronchial needle aspiration
 Mediastinoscopy
 Video-assisted thoracoscopy
Clinical Division of Oncology
Department of Medicine I
“Normal mediastinum”
Central disease
Peripheral tumor
Mediastinoscopy
& Throacotomy
(Mediastinoscopy?)
& Thoracotomy
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 6th ed. 2001;925-983.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
TNM stage grouping
Occult carcinoma
Tx
N0
M0
Stage 0
Tis
N0
M0
Stage Ia
T1
N0
M0
Stage Ib
T2
N0
M0
Stage IIa
T1
N1
M0
Stage IIb
T2
T3
N1
N0
M0
M0
T1
T2
T3
T3
N2
N2
N1
N2
M0
M0
M0
M0
Stage IIIb
Any T
T4
N3
Any N
M0
M0
Stage IV
Any T
Any N
M1
Stage IIIa
Clinical Division of Oncology
Department of Medicine I
AJCC® Cancer Staging Manual, 5th edition (1997)
published by Lippincott-Raven Publishers, Philadelphia,
Pennsylvania.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Stage I
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Stage II
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Stage IIIa
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
NON-SMALL CELL
LUNG CANCER
Any T, N3, M0
Scalene
Supraclavicular
Stage IIIb
T4, Any N, M0
Any N
T4
Any T
N3: contralateral mediastinal,
contralateral hilar, ipsilateral, or
contralateral scaline or supraclavicular
nodesDivision
involvedof Oncology
Clinical
Department of Medicine I
T (any size) invading mediastinum, heart,
great vessels, trachea, esophagus,
vertebral body, or carina
or T+ malignant pleural
effusion
Medical
University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Stage IV
Clinical Division of Oncology
Department of Medicine I
Mountain CF. Chest. 1997;111:1710-1717.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Spread to lymph nodes
Clinical Division of Oncology
Department of Medicine I
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology.
6th ed. 2001;925-983.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Local and distal spread
Clinical Division of Oncology
Department of Medicine I
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology.
6th ed. 2001;925-983.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Stages at presentation
7%
Stage II
31%
Stage III
24%
Stage I
38%
Stage IV
Clinical Division of Oncology
Department of Medicine I
Fry WA, et al. Cancer. 1996;77:1949-1995.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Adverse prognostic factors
Early-stage disease (I, II, resectable Stage III)
• Large tumor size; presence of lymph node metastases
• Age >60 years
• Male gender
• Wedge resection rather than lobectomy or pneumonectomy
• Mucin expression
Advanced-stage disease (unresectable Stage III and IV)
• Advanced pretreatment stage
• Poor performance status
• Weight loss
• Male gender
• Elevated serum lactate dehydrogenase
• Bone and liver metastases (?)
Clinical Division of Oncology
Department of Medicine I
Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology.
6th ed. 2001;925-983.
Medical University of
Vienna, Austria
NON-SMALL CELL LUNG CANCER
Survival by stage
120
100
80
60
40
20
0
0
1
2
3
4
5
I
100
79
54
64
48
42
II
100
65
42
32
28
22
III
100
34
15
9
7
5
IV
100
24
9
6
4
3
Clinical Division of Oncology
Department of Medicine I
Years
Fry WA, et al. Cancer. 1996;77:1953.
Medical University of
Vienna, Austria
LUNG CANCER
Selected paraneoplastic
syndromes
Hematologic
Endocrine
Hypercalcemia
Cushing’s syndrome
Syndrome of inappropriate
antidiuretic hormone
Carcinoid syndrome
Gynecomastia
Neurologic
Encephalopathy
Peripheral neuropathy
Lambert-Eaton syndrome
Skeletal
Clubbing of digits
Pulmonary hypertrophic
osteoarthropathy
Clinical Division of Oncology
Department of Medicine I
Anemia
Thrombocytosis
Thrombocytopenia
Disseminated intravascular
coagulation
Cutaneous
Hyperkeratosis
Dermatomyositis
Other
Nephrotic syndrome
Secretion of vasoactive
intestinal peptide with diarrhea
Anorexia or cachexia
Ginsberg RJ, et al. Cancer: Principles and Practices of
Oncology. 6th ed. 2001;925-983.
Medical University of
Vienna, Austria
LUNG CANCER
Pancoast’s syndrome I
Symptoms associated with superior pulmonary
sulcus tumor
Shoulder and arm pain
Horner’s syndrome (ipsilateral ptosis, miosis,
anhidrosis)
Weakness and atrophy of hand muscles
Causes
Non-small cell lung cancer
Other neoplasms (thoracic, hematologic)
Infectious diseases
Clinical Division of Oncology
Department of Medicine I
Arcasoy SM, et al. N Engl J Med. 1997;337:1370-1376.
Medical University of
Vienna, Austria
LUNG CANCER
Pancoast’s syndrome II
Diagnosis through percutaneous transthoracic needle
biopsy
Generally Stage IIb or Stage III (a or b), T3 lesions
Factors indicating poor prognosis:
Extension of tumor into base of neck
Mediastinal lymph node involvement
Presence of Horner’s syndrome
Median survival 7 to 31 months
5-year survival 20%-35%
Relapse is common, often as brain metastases
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Incidence of histologic types
Mixed small cell/
large cell carcinoma
4-6%
Pure small cell
carcinoma
>90%
Combined small
cell carcinoma
<1%
Clinical Division of Oncology
Department of Medicine I
Lassen U, et al. Cancer Treatment. 1995;414-420.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Symptoms
Primary tumor
Regional metastases
• Cough
• Dyspnea
• Superior vena cava
syndrome
• Wheezing
• Hoarseness
• Hemoptysis
• Dysphagia
• Chest pain
Distant metastases
• Postobstructive
pneumonia
• Bone pain
Clinical Division of Oncology
Department of Medicine I
• CNS symptoms
(headache, double vision)
Glassberg AB, et al. Everyone’s Guide to Cancer Therapy.
1997;540-544.
Murren J, et al. Cancer: Principles & Practice of Oncology. 6th
ed. 2001;983-1018.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Differentiating signs from
NSCLC
More common in
SCLC
• Hilar and mediastinal
invasion
• Regional adenopathy
• Atelectasis
• Pneumonitis
Clinical Division of Oncology
Department of Medicine I
Less common in
SCLC
• Peripheral location
• Pleural effusion
• Chest wall
involvement
Murren J, et al. Cancer: Principles & Practice of Oncology. 6th
ed. 2001;983-1018.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Staging
Limited disease
• Disease confined to one hemithorax and regional
lymph nodes: hilar, ipsilateral, and contralateral
mediastinal; supraclavicular (controversial)
• Ipsilateral pleural effusion (controversial)
Extensive disease
• Any disease beyond limited disease sites
Clinical Division of Oncology
Department of Medicine I
Lassen U, et al. Cancer Treatment. 1995;414-420.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Extrathoracic disease sites at
presentation
Percentage with Finding
Bone
27-41%
Liver
21-27%
Bone marrow
15-30%
Adrenals
5-31%
Brain
10-14%
Retroperitoneal lymph nodes
3-12%
Mediastinal lymph nodes
66-80%
Supraclavicular lymph nodes
17%
Soft tissue
5%
Contralateral lung
1-12%
Pleural effusion
16-20%
Clinical Division of Oncology
Murren J, et al. Cancer: Principles & Practice of Oncology.
Department of Medicine I
6th ed. 2001;983-1018.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Evaluation of disease
extent I
Minimum Evaluation
• History and physical examination
• Chest radiograph ± CT
• Liver function tests and examination ± liver scan
• Evaluation of bone pain and alkaline
phosphatase ± bone scan
• Neurologic history and examination ± brain CT
• Platelet count or leukoerythroblastic peripheral
blood smear
Clinical Division of Oncology
Department of Medicine I
Ihde DC, et al. Cancer: Principles & Practice of Oncology. 5th
ed. 1997.
Murren J, et al. Cancer: Principles & Practice of Oncology. 6th
ed. 2001;983-1018.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Evaluation of disease
extent II
Evaluation for Stage Adapted Therapy
•
History and physical examination
•
Chest radiograph ± CT ± bronchoscopy
•
Liver function tests and liver scan ± liver biopsy
•
Bone scan
•
Bone marrow aspiration (?)
•
± Brain CT
Evaluation for Surgical Resection (in addition to above)
•
Fiberoptic bronchoscopy
•
Chest CT and mediastinoscopy
•
PET (?)
Clinical Division of Oncology
Department of Medicine I
Ihde DC, et al. Cancer: Principles & Practice of Oncology.
5th ed. 1997.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Prognostic factors
Stage
Performance status
Gender
Age
Histological subclassification
Bone marrow metastases
Liver metastases
CNS involvement
Blood biochemistry, especially lactate dehydrogenase
Clinical Division of Oncology
Department of Medicine I
Lassen U, Hansen HH. Cancer Treatment. 4th ed. 1995.
Medical University of
Vienna, Austria
SMALL CELL LUNG CANCER
Survival by stage
Median Survival –
Untreated Patients
(wk)
Median Survival –
Treated Patients
(mo)
5-Year Survival
(%)
12
14-20
10%-20%
5
8-12
3%-5%
Limited disease
Extensive disease
Clinical Division of Oncology
Department of Medicine I
Ihde DC, et al. Cancer: Principles & Practice of Oncology.
1997;911-948.
Lassen U, et al. Cancer Treatment. 1995;414-420.
Soriano AF, et al. Current Cancer Therapeutics. 1998;177-191.
Medical University of
Vienna, Austria
LUNG CANCER
Risk factors for lung cancer
 Cigarettes
(Variables: age at onset of smoking,
duration of smoking period, number of daily smoked
cigarettes)
 Cigar- and pipe smoking
 Passive smoking
 Radon
 Asbestos
 Air pollution (e.g. diesel combustion)
 Lung diseases (e.g. Tubercolosis)
 Earlier lung cancer
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Histologic diagnosis of
lung cancer
• Bronchoscopy
• Needle biopsy
• Thoracozentesis
• Thoracotomy
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Therapy
General rules:
• Small cell lung cancer is sensitive to chemotherapy;
NSCLC to a lesser extent.
• Surgery is the treatment of choice in localized
NSCLC, but not SCLC.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Therapies for lung cancer
• Surgery
• Chemotherapy
• Radiation
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CENTRAL EUROPEAN COOPERATIVE
ONCOLOGY GROUP (CECOG)
CONSENSUS DEVELOPMENT
CONFERENCE ON MEDICAL
TREATMENT OF NON SMALL
CELL LUNG CANCER.
Vienna, November 30 - December 1, 2001
Editors: C. C. Zielinski, M. Krainer and F. Hirsch
Lung Cancer, in press (2002)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CENTRAL EUROPEAN COOPERATIVE
ONCOLOGY GROUP (CECOG)
CONSENSUS DEVELOPMENT CONFERENCE ON
MEDICAL TREATMENT OF NSCLC.
PARTICIPANTS
R.L. AKEHURST, T. BEINERT, J. CRAWFORD, L. CRINO, J. DEBUS,
F. ECKERSBERGER, J. FISCHER, V. GEORGOULIAS, C. GRIDELLI, F.R. HIRSCH, J. JASSEM,
P. KOSMIDIS, M. KRAINER, M. KRZAKOWSKI, Ch. MANEGOLD,
J. NIKLINSKI, R. PIRKER, J.L. PUJOL, G. SCAGLIOTTI, N. THATCHER,
M. TONATO, N. van ZANDWIJK, C.C. ZIELINSKI, S. ZÖCHBAUER, M. ZWITTER.
SUPPORTING INSTITUTIONS
CENTRAL EUROPEAN COOPERATIVE ONCOLOGY GROUP (CECOG)
EUROPEAN SCHOOL OF ONCOLOGY (ESO)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC.
1. INDUCTION (NEOADJUVANT) CHEMOTHERAPY
2. ADJUVANT CHEMOTHERAPY
3. CHEMOTHERAPY OF ADVANCED DISEASE
4. SECOND-LINE CHEMOTHERAPY
4. SUPPORTIVE CARE
5. FUTURE DEVELOPMENTS
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
INDUCTION THERAPIES FOR MARGINALLY
OPERABLE PATIENTS.
• CHEMORADIOTHERAPY PILOTED DURING 1980’s
FOR STAGES IIIA / B
• CHEMOTHERAPY ALONE PILOTED DURING 1980’s
TO 1990’s
• NEW PLATINUM DOUBLETS (END 1990’s)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
RECENT AGENTS FOR INDUCTION
(NEOADJUVANT) CHEMOTHERAPY.
GEMCITABINE / CISPLATIN
PACLITAXEL / CARBOPLATIN
DOCETAXEL / CISPLATIN
DOCETAXEL
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
RATIONALE FOR INDUCTION
(NEOADJUVANT) CHEMOTHERAPY.
• REDUCTION OF TUMOR SIZE MAY FACILITATE SURGERY
AND IMPROVE COMPLETE RESECTION RATES.
• MICROMETASTASES MAY BE ERADICATED.
• RESPONSE OF THE PRIMARY TUMOR MAY INDICATE
OVERALL EFFICACY OF CHEMOTHERAPY.
• INDUCTION CHEMOTHERAPY MAY REDUCE THE STIMULUS
TO RESIDUAL TUMOR CELLS BY GROWTH FACTORS
RELEASED FROM THE PRIMARY TUMOR.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
PHASE II TRIALS ON INDUCTION
(NEOADJUVANT) CHEMOTHERAPY.
• FEASIBILITY AND EFFICACY IN STAGE IIIA DISEASE WITH
N2 INVOLVEMENT IN MULTIPLE PHASE II TRIALS
INVOLVING >1.000 PATIENTS.
• AVERAGE RESPONSE RATE OF 62%, THORACOTOMY
PERFORMED IN 55% OF PATIENTS WITH 49%
SUCCESSFULLY RESECTED.
• CR: 10-20%, MEDIAN SURVIVAL: 16.5 MONTHS,
5-YR.-SURVIVAL IN RESPONDING PATIENTS: 30-50%.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
PHASE III TRIALS ON INDUCTION
(NEOADJUVANT) CHEMOTHERAPY.
• TWO-FOLD INCREASE IN MEDIAN SURVIVAL IN
COMPARISON TO SURGERY ALONE.
• FAVORABLE RESULTS PARTICULARLY IN PATIENTS WITH
DOWN-STAGING OF MEDIASTINAL LYMPH NODES AND
QUALIFICATION FOR COMPLETE SURGICAL RESECTION.
• GEMCITABINE, DOCETAXEL AND PACLITAXEL IN
COMBINATION WITH CISPLATIN HAVE YIELDED PROMISING
RESULTS.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADJUVANT CHEMOTHERAPY
• ATTEMPTED IN COMPLETELY RESECTED PATIENTS WITH
STAGE I, II OR IIIA DISEASE.
• SURVIVAL FIGURES NOT SIGNIFICANT.
• ADJUVANT CHEMOTHERAPY CANNOT BE RECOMMENDED
AS STANDARD OF CARE IN PATIENTS WITH DISEASE
STAGES I, II, IIIA N1.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
RECOMMENDATIONS FOR EARLY NSCLC I
• SURGERY REMAINS THE MAINSTAY OF
TREATMENT.
• RANDOMISED CLINICAL TRIALS EXPLORING
THE BENEFIT OF NEOADJUVANT
CHEMOTHERAPY ARE STONGLY
RECOMMENDED.
• CAREFUL ANALYSIS OF FINAL DATA OF
ADJUVANT CHEMOTHERAPY TRIALS
NEEDED.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
RECOMMENDATIONS FOR EARLY NSCLC II.
• ROLE OF PROPHYLACTIC CRANIAL
RADIOTHERAPY?
•TISSUE BANKING AND COLLECTION OF BLOOD.
•ROLE OF TARGETED BIOLOGICAL THERAPIES?
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
LOCALLY ADVANCED NSCLC.
• ADDITION OF PLATINUM-BASED CHEMOTHERAPY SHOULD
STRONGLY BE CONSIDERED IN SELECTED PATIENTS
ELIGIBLE FOR RADIOTHERAPY.
• SELECTION SHOULD BE BASED UPON PERFORMANCE
STATUS, WEIGHT LOSS AND EXTENT OF DISEASE IN
THE THORAX.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADVANCED NSCLC.
• PLATINUM-BASED CHEMOTHERAPY HAS TO BE
REGARDED STANDARD TREATMENT FOR PATIENTS WITH
ACCEPTABLE PERFORMANCE STATUS (WHO GRADES 0-1).
CYTOTOXIC TREATMENT IS SUPERIOR OVER BSC.
• NO EVIDENCE THAT DOSES >75 - 80 MG CISPLATIN / M2
INCREASE RESPONSE RATES.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADVANCED NSCLC.
• IN RANDOMIZED TRIALS, A MODEST IMPROVEMENT IN
RESPONSE RATE HAS BEEN OBTAINED WITH NEW
CYTOTOXIC DRUGS.
•PRESENT PLATINUM-BASED CHEMOTHERAPY CAN
INDUCE MEDIAN SURVIVAL OF 8-9 MONTHS AND 1-YR.
SURVIVAL OF 35-40% IN STAGE IIIB AND IV DISEASE.
• PLATINUM-FREE CHEMOTHERAPY IN CASE OF PLATINUMCONTRAINDICATIONS IS POSSIBLE.
• NO EVIDENCE FOR THE SUPPORT OF TRIPLE-DRUG
CHEMOTHERAPY.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADVANCED NSCLC.
SINGLE-AGENT FIRST-LINE CHEMOTHERAPY
... WITH GEMCITABINE OR NAVELBINE IS APPROPRIATE
FOR PALLIATION IN
* PATIENTS WITH WHO PERFORMANCE STATUS 2,
* THE ELDERLY,
* THE PRESENCE OF PLATINUM-CONTRAINDICATIONS.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADVANCED NSCLC.
SECOND-LINE CHEMOTHERAPY
... SHOULD BE CONSIDERED FOR CHEMOTHERAPEUTICALLY
PRETREATED PATIENTS WITH GOOD PERFORMANCE STATUS
IN ORDER TO PROLONG SURVIVAL AND IMPROVE QUALITY
OF LIFE.
SECOND-LINE DOCETAXEL (75MG / M2) IS RECOMMENDED.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADVANCED NSCLC.
DURATION OF CHEMOTHERAPY
• IN CASE OF NON-PROGRESSION AND LACK OF SEVERE
TOXICITY, THE ADMINISTRATION OF FOUR TO SIX CYCLES OF
CHEMOTHERAPY IS RECOMMENDED.
• THERE IS NO EVIDENCE THAT PROLONGATION OF
TREATMENT HAS AN IMPACT UPON SURVIVAL.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
SUPPORTIVE CARE.
1. APPROPRIATE SUPPORTIVE CARE.
2. ERYTHROPOIETIN MAY BE CONSIDERED IN CASE OF
ANEMIA.
3. ROUTINE US OF CSFs IS NOT RECOMMENDED. CSFs MAY BE
CONSIDERED IN PRESENT OR PAST EPISODES OF FEBRILE
NEUTROPENIA.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
FUTURE DEVELOPMENTS.
1. MOLECULAR TARGETED THERAPIES.
2. DIAGNOSIS OF EARLY LESIONS BY NEW DEVELOPMENTS IN
TECHNOLOGY.
3. TREATMENT OPTIMISATION FOR SMALL (<1 CM) LESIONS.
4. TUMOR TISSUE BANKING.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Influence of stage
on choice of therapy
STAGE
T
N
M
Tis
T1
T2
T1
T2
T3
N0
N0
N0
N1
N1
N0
M0
M0
M0
M0
M0
M0
Resection
IA
IB
IIA
IIB
Primary Chemotherapy
IIIA
T1,T2
N2
T3
N1, N2
IIIB
Any T
N3
T4
Any N
IV
Any T
Any N
Clinical Division of Oncology
Department of Medicine I
M0
M0
M0
M0
M1
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
RECOMMENDATIONS FOR NSCLC AT AN
EARLY STAGE
Surgery is the therapy of choice at
an early operable stage
Clinical Division of Oncology
Department of Medicine I
CENTRAL EUROPEAN COOPERATIVE
ONCOLOGY GROUP
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
ADVANCED STAGE OF DISEASE
• Platin-containing chemotherapy represents the
therapy of choice for patients with acceptable
performance status (WHO grade 0-1). Cytotoxic
chemotherapy is significant better than “best
supportive care”.
• Platin-containing chemotherapy, available at
present, can induce a median survival of 8-9 months
and 1-year survival of 35-40%.
Clinical Division of Oncology
Department of Medicine I
CENTRAL EUROPEAN COOPERATIVE
ONCOLOGY GROUP
Medical University of
Vienna, Austria
CONSENSUS DEVELOPMENT CONFERENCE
ON MEDICAL TREATMENT OF NSCLC:
SUPPORTIVE CARE.
The extent of „SUPPORTIVE CARE“
with sufficient pain therapy and measures
for an increase in quality of life are to be
applied according to the situation.
Clinical Division of Oncology
Department of Medicine I
CENTRAL EUROPEAN COOPERATIVE
ONCOLOGY GROUP
Medical University of
Vienna, Austria
„BEST SUPPORTIVE CARE“
 Pain management
 Measures for reduction of vital handicaps (leg oedema,
ascites, pleural effusion, etc.)
 Measures for an increase in quality of life (anaemia –
erythropoietin, immobility – physical therapy, constipation –
laxatives, etc.)
 Loss of appetite
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Pain management
 BY THE CLOCK
 BY THE MOUTH
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
PYRAMID OF PAIN
THERAPY
 NSAR
morphinreceptor-agonists (tramadol)
 oral morphines or morphones
 transcutaneous depotsystems (fentanyl)
 adjuvants (antidepressants, steroids)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Chemotherapy in SCLC
Established Protocols:
Cisplatin 25mg/m2 day 1-3, Etoposid 100mg/m2
day 1-3
Adriamycin 50mg/m2 day 1, Cyclophosphamid
750mg/m2 day 1, Oncovin 2mg day 1
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Chemotherapy in SCLC
Noda et al, J Clin Oncol 2002
230 Pat. with SCLC (ED):
Group A: Irinotecan/Cisplatin
Group B: Etoposid/Cisplatin
Median Survival 12.8 (I/C) vs.
9.4 Months (E/C)
Further studies required!
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
LUNG CANCER
Future
• Prevention of smoking
• Identification of patients with high risk
(molecular markers)
• Early diagnosis
• Molecular Targets (individual therapy)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria