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Niti Charat
MD, in trainee programme
Internal medicine department
Khon Kaen Hospital
All data in this material is based on...
Tobacco
GeneticEnvironment
National lung screening trial
(NLST)
- 53454 subject, age 55-74,
- Tobacco at least 30 packyears
- Result show 20% reducti...
A 50‐yr-old female with irregular cavitating
squamous cell carcinoma in the right upper lobe (arrows).
2,3 | 5,7
First line
Second line
Third line
Maintenance
Not approved
1970 1980 1990 2000
Median
OS (mos)
12+
~ 6
~ 2-4
BSC Single-ag...
STAGE Treatment
I A Surgery
I B Surgery Adjuvant Chemotherapy
II A Surgery Adjuvant Chemotherapy
II B Surgery Adjuvant Che...
Stage IV disease
histological
Squamous Platinum doublet Maintainance
Non squamous
Gene alteration
PRESENT
Targeted therapy...
Results shown for cisplatin-based regimens only (11 trials) NSCLC Collaborative Group
BMJ 1995;311:899–909
100
80
60
40
20...
0
5
10
15
20
25
30
35
Response rate (%) 1-yr survival (%)
two-drug regimens single agent
26%
13%
35% 30%
JAMA 2004; 292:47...
RANDOMIZE
Cisplatin +
Paclitaxel
Cisplatin + Gemcitabine
Cisplatin +
Docetaxel
Carboplatin + Paclitaxel
N Engl J Med 2002;...
1.0
0.8
0.6
0.4
0.2
0
0 5 10 15 20 25 30
Time (months)
Cisplatin/paclitaxel
Cisplatin/gemcitabine
Cisplatin/docetaxel
Carb...
* Non-squamous=adenocarcinoma, large cell carcinoma, and other/indeterminate NSCLC histology
Non-squamous* (n=1252) Squamo...
TS
• SCLC – High TS
• Squamous – High TS
• Adeno – Low TS
Bhattacharjee PNAS 2001
Recombinant
humanized
monoclonal
antibody to
VEGF-A
R
A
N
D
O
M
I
Z
E
Paclitaxel 200 mg/m2 IV
Carboplatinum AUC 6 q 21d
X6 cycles
Paclitaxel 200 mg/m2 IV +
Carboplatinum AUC ...
HR: 0.79, 0.67-0.92
P = .003
Pac/carbo + bev, n=434 51% 23%
Pac/carbo, n=444 44% 15%
0.0
0.2
0.4
0.6
0.8
1.0
Proportionsur...
PC
n=427
PCB
n=420
Hemorrhage
Hemoptysis 0 5
GI Bleed 1 2
Neutropenic Fever 1 5
CNS 0 2*
Pulmonary Embolus 0 1
Total 2 15
...
Limited disease
(within a tolerable radiation field)
Extensive disease
(distant metastases)
Ki – 67
Limited disease
Etoposide + cisplatin or carboplatin (4-6
cycle)
CCRT start with first or second cycle (twice
daily to 450...
Does PCI have a role in patients with
ED-SCLC after chemotherapy?
Study Design
PCI
20-30 Gy in
5-12 fractions
No PCI
RandomAny response
Stratification: Performance score and Institute
< 5 ...
(months)
0 4 8 12 16 20 24 28 32 36
0
10
20
30
40
50
60
70
80
90
100
PCI
Control
1 year: 14.6% vs. 40.4%
HR: 0.27 (0.16-0....
(months)
0 4 8 12 16 20 24 28 32 36
0
10
20
30
40
50
60
70
80
90
100
P=0.2699
Control
PCI
Extracranial progression
(months)
0 3 6 9 12 15 18 21 24 27
0
10
20
30
40
50
60
70
80
90
100
PCI
Control
6 months: 23.4% vs. 15.5%
HR: 0.76 (0.59-0...
(months)
0 4 8 12 16 20 24 28 32 36
0
10
20
30
40
50
60
70
80
90
100
PCI
Control
1 year: 27.1% vs. 13.3%
HR: 0.68 (0.52-0....
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
Lung cancer : Topic review
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Lung cancer : Topic review

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Topic review of lung cancer


เืนื้อหา
1: CA lung categories
2: Predisposing factor
3 Charactoristic
4 treatment

Published in: Health & Medicine
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Lung cancer : Topic review

  1. 1. Niti Charat MD, in trainee programme Internal medicine department Khon Kaen Hospital All data in this material is based on current evidenced until December 11,2015
  2. 2. Tobacco GeneticEnvironment
  3. 3. National lung screening trial (NLST) - 53454 subject, age 55-74, - Tobacco at least 30 packyears - Result show 20% reduction in lung cancer mortality
  4. 4. A 50‐yr-old female with irregular cavitating squamous cell carcinoma in the right upper lobe (arrows).
  5. 5. 2,3 | 5,7
  6. 6. First line Second line Third line Maintenance Not approved 1970 1980 1990 2000 Median OS (mos) 12+ ~ 6 ~ 2-4 BSC Single-agent platinum Doublets Bevacizumab + PC Carboplatin* 1989 Erlotinib Pemetrexed 2004 Docetaxel 1999 Paclitaxel Gemcitabine 1998 Vinorelbine 1994 Docetaxel 2002 Bevacizumab 2006 Gefitinib 2003 Standard therapies *Label does not include NSCLC-specific indication Pemetrexed 2008/2009 Histology-directed therapy ~ 8-10 Cisplatin* 1978 1. FDA Web site. 2. NCCN. Clinical practice guidelines in oncology. v.3.2011. 3. Schrump, et al. Non-small cell lung cancer. In: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
  7. 7. STAGE Treatment I A Surgery I B Surgery Adjuvant Chemotherapy II A Surgery Adjuvant Chemotherapy II B Surgery Adjuvant Chemotherapy III A Surgery Adjuvant Chemotherapy III B Concurrent Chemotherapy Radiotherapy IV Palliative Chemotherapy
  8. 8. Stage IV disease histological Squamous Platinum doublet Maintainance Non squamous Gene alteration PRESENT Targeted therapy Gene alteration ABSENT Yes Platinum doublet +bevacizumab maintainance No Platinum doublet Maintainance
  9. 9. Results shown for cisplatin-based regimens only (11 trials) NSCLC Collaborative Group BMJ 1995;311:899–909 100 80 60 40 20 0 Survival(%) 0 6 12 1824 Time from randomization (months) Supportive care + CT Supportive care
  10. 10. 0 5 10 15 20 25 30 35 Response rate (%) 1-yr survival (%) two-drug regimens single agent 26% 13% 35% 30% JAMA 2004; 292:470 Two-drugs: significantly increase in both response rate and survival
  11. 11. RANDOMIZE Cisplatin + Paclitaxel Cisplatin + Gemcitabine Cisplatin + Docetaxel Carboplatin + Paclitaxel N Engl J Med 2002; 346:92
  12. 12. 1.0 0.8 0.6 0.4 0.2 0 0 5 10 15 20 25 30 Time (months) Cisplatin/paclitaxel Cisplatin/gemcitabine Cisplatin/docetaxel Carboplatin/paclitaxel OSestimate Schiller, et al. NEJM 2002 Median survival time ~ 8 months • Overall RR~19% • 1-yr survival~33%
  13. 13. * Non-squamous=adenocarcinoma, large cell carcinoma, and other/indeterminate NSCLC histology Non-squamous* (n=1252) Squamous (n=473) Pemetrexed + cisplatin Median OS: 11.0 mos Gemcitabine + cisplatin Median OS: 10.1 mos HR=0.844 (95% CI: 0.74–0.96) P=0.011 Pemetrexed + cisplatin Median OS: 9.4 mos Gemcitabine + cisplatin Median OS: 10.8 mos HR=1.229 (95% CI: 1.00–1.51) P=0.051 Survival Time (months) Survival Time (months) 100 90 80 70 60 50 40 30 20 10 0 SurvivalProbability(%) 100 90 80 70 60 50 40 30 20 10 0 SurvivalProbability(%) Ciuleanu, et al. ASCO 2008
  14. 14. TS • SCLC – High TS • Squamous – High TS • Adeno – Low TS Bhattacharjee PNAS 2001
  15. 15. Recombinant humanized monoclonal antibody to VEGF-A
  16. 16. R A N D O M I Z E Paclitaxel 200 mg/m2 IV Carboplatinum AUC 6 q 21d X6 cycles Paclitaxel 200 mg/m2 IV + Carboplatinum AUC 6 q 21d X6 cycles Bevacizumab 15mg/kg q3 wk til PD Stratification by: • Stage (IIIB or IV) • Geographic region Sandler. NEJM 2006; 355: 2542 IIIB and IV non-squamous No brain mets No hemoptysis No prior chemotherapy
  17. 17. HR: 0.79, 0.67-0.92 P = .003 Pac/carbo + bev, n=434 51% 23% Pac/carbo, n=444 44% 15% 0.0 0.2 0.4 0.6 0.8 1.0 Proportionsurviving 0 6 42 4818 30 12 mo 24 mo 12 24 36 Months 12.3 10.3 Sandler AB, et al. New Engl J Med. 2006;355:2542-2550. ~37% of patients with advanced NSCLC are eligible to receive bevacizumab, <20% if also exclude age ≥70 years Non-Squamous histology, no hemoptysis, brain metastases
  18. 18. PC n=427 PCB n=420 Hemorrhage Hemoptysis 0 5 GI Bleed 1 2 Neutropenic Fever 1 5 CNS 0 2* Pulmonary Embolus 0 1 Total 2 15 Sandler AB, et al. New Engl J Med. 2006;355:2542-2550.
  19. 19. Limited disease (within a tolerable radiation field) Extensive disease (distant metastases)
  20. 20. Ki – 67
  21. 21. Limited disease Etoposide + cisplatin or carboplatin (4-6 cycle) CCRT start with first or second cycle (twice daily to 4500 cGy or once- daily to 6300 cGy Extensive disease Etoposide + cisplatin or carboplatin (4-6 cycle) Complete /partial response • PCI • Observe progression with CT • Smoke cessation • If no evidence of dz, >3yr, surveillance for secondary primary Progression Refractory Topotecan CAV Paclitaxel Docetaxel Irinotecan Gecitabine Temozolomide Vinorelbine Supportive care Sensitive Topotecan CAV Re-challence first line reg. if initial response >6month
  22. 22. Does PCI have a role in patients with ED-SCLC after chemotherapy?
  23. 23. Study Design PCI 20-30 Gy in 5-12 fractions No PCI RandomAny response Stratification: Performance score and Institute < 5 weeks 4-6 weeks No response Chemotherapy (4-6 cycles) Slotman et al. NEJM 2007
  24. 24. (months) 0 4 8 12 16 20 24 28 32 36 0 10 20 30 40 50 60 70 80 90 100 PCI Control 1 year: 14.6% vs. 40.4% HR: 0.27 (0.16-0.44) p<0.001 Symptomatic brain metastases
  25. 25. (months) 0 4 8 12 16 20 24 28 32 36 0 10 20 30 40 50 60 70 80 90 100 P=0.2699 Control PCI Extracranial progression
  26. 26. (months) 0 3 6 9 12 15 18 21 24 27 0 10 20 30 40 50 60 70 80 90 100 PCI Control 6 months: 23.4% vs. 15.5% HR: 0.76 (0.59-0.96) p=0.02 Failure-free survival
  27. 27. (months) 0 4 8 12 16 20 24 28 32 36 0 10 20 30 40 50 60 70 80 90 100 PCI Control 1 year: 27.1% vs. 13.3% HR: 0.68 (0.52-0.88) p=0.003 Overall survival

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